IMR Press / FBL / Volume 28 / Issue 4 / DOI: 10.31083/j.fbl2804071
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Nanoparticles: Properties, applications and toxicities
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    Liang-Chuan Lai
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Abstract
Keywords
1. Introduction
2. The Relationship between LncRNAs and Ovarian Cancer
3. Clinical Significance of LncRNAs in Ovarian Cancer
4. Discussion
Author Contributions
Ethics Approval and Consent to Participate
Acknowledgment
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References
Open Access Review
Long Noncoding RNAs in Ovarian Cancer—Functions and Clinical Applications
Lili Zhong1, Xin Li1, Yicun Wang1, Bin Liu2, Xiangfu Ding3,*,†, Yinlong Zhao4,*,†
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1 Department of Research Center, Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, 130041 Changchun, Jilin, China
2 Department of Breast Surgery, The Second Hospital of Jilin University, 130041 Changchun, Jilin, China
3 Department of Thyroid Surgery, The Second Hospital of Jilin University, 130041 Changchun, Jilin, China
4 Department of Nuclear Medicine, The Second Hospital of Jilin University, 130041 Changchun, Jilin, China
*Correspondence: jdeyjzxwkdxf@163.com (Xiangfu Ding); yinlong@jlu.edu.cn (Yinlong Zhao)
†These authors contributed equally.
Front. Biosci. (Landmark Ed) 2023, 28(4), 71; https://doi.org/10.31083/j.fbl2804071
Submitted: 17 October 2022 | Revised: 23 December 2022 | Accepted: 26 December 2022 | Published: 6 April 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
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Abstract

Long noncoding RNAs (lncRNAs) are RNA molecules with a length of more than 200 nt that have been discovered in recent years. LncRNAs can participate in regulating gene expression and various biological activities through multiple pathways, such as at the epigenetic level, transcriptional level, and posttranscriptional level. In recent years, with the increasing understanding of lncRNAs, a large number of studies have shown that lncRNAs are closely related to ovarian cancer and participate in its occurrence and development, providing a new method to investigate ovarian cancer. In this review, we analyzed and summarized the relationship between various lncRNAs and ovarian cancer in terms of occurrence, development, and clinical significance, in order to provide a theoretical basis for basic research and clinical application of ovarian cancer.

Keywords
long noncoding RNAs
ovarian cancer
expression disorder
diagnosis
therapy
prognosis
1. Introduction

Long noncoding RNAs (lncRNAs), which have a length of more than 200 nt, are mainly located in the nucleus or cytoplasm and are transcribed by RNA polymerase. They are a kind of noncoding RNA molecules with high tissue and organ specificity [1, 2, 3]. The mechanisms and types of lncRNAs action are complex: (a) they can inhibit translation and degradation through complementary binding with mRNA bases; (b) as competing endogenous RNAs (ceRNAs), they can competitively bind to microRNAs to regulate the expression of target genes; (c) they recruit chromatin remodeling proteins to specific genomic sites to regulate chromatin status, participate in chromatin modification, and regulate gene expression at the epigenetic level; (d) they can promote the cyclization of enhancers and activate gene expression, with enhancer activity; (e) they can act as transcriptional regulatory factors and play a role in transcriptional regulation; and (f) they can conduct post-transcriptional regulation through splicing and translation control [4, 5, 6]. Ovarian cancer (OC) is one of the most common malignancies of the female reproductive system, and its incidence and mortality rates have remained high for many years. OC seriously endangers the health of women worldwide; statistically, there are nearly 240,000 new OC patients worldwide every year, and approximately 140,000 women die of OC every year [7, 8]. In recent years, some specific lncRNAs have been found to be abnormally expressed in OC cells and tissues, and closely related to the occurrence and development of OC. These findings have brought new enlightenment to the study of OC [9, 10, 11, 12, 13, 14, 15]. In this review, we summarized and analyzed the relevant studies and reports on the relationship between lncRNAs and OC in recent years to provide a reliable theory for basic research, clinical diagnosis, therapy, and efficacy monitoring of OC.

2. The Relationship between LncRNAs and Ovarian Cancer
2.1 Some LncRNAs can Promote the Occurrence and Development of Ovarian Cancer

In recent years, a variety of lncRNAs have been found to be abnormally expressed in OC, which can promote the occurrence and development of OC [16, 17, 18, 19, 20]. The lncRNAs ROR, SRA, H19, UCA1 and PTAR have been reported to promote the occurrence and development of OC by regulating epithelial-mesenchymal transformation (EMT) [21, 22, 23, 24, 25]. Wang et al. [26] detected the expression of lncRNA RHPN1-AS1 in tissues samples of 86 epithelial ovarian cancer (EOC) patients and 9 EOC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that the expression of lncRNA RHPN1-AS1 was significantly higher in EOC cancer tissues and cell lines than in control samples. Further mechanistic studies demonstrated that lncRNA RHPN1-AS1 binds to the target gene miR-596, resulting in the upregulation of leucine zipper EF-hand domain transmembrane protein 1 (LETM1) and activation of the FAK/PI3K/AKT signaling pathway, which promote the proliferation, invasion, and migration of EOC cells. The lncRNA RHPN1-AS1 accelerates the progression of OC. Pei et al. [27] found that lncRNA DANCR expression level in OC tissues was significantly higher than that in control samples, and lncRNA DANCR overexpression could promote proliferation, migration and invasion of OC cells. Mechanistic experiments showed that DANCR overexpression resulted in significant downregulation of UPF1, and the expression level of UPF1 was negatively correlated with the expression of DANCR. LncRNA DANCR could enhance the proliferation, migration, and invasion of OC cells by downregulating UPF1 and promoting the progression of OC. Cao et al. [28] found that the lncRNA LBX2-AS1 expression level was higher in OC samples and was related to tumor growth, metastasis, and low survival rate. Knocking out lncRNA LBX2-AS1 inhibited the proliferation, migration, and invasion of OC cells. Further studies confirmed that lncRNA LBX2-AS1 could directly interact with miR-455-5p and miR-491-5p as competing endogenous RNA (ceRNA), regulate the expression of E2F2 cancer-promoting gene and play a role as an oncogenic lncRNA in OC. Wang et al. [29] found that lncRNA CDKN2B-AS1 was significantly overexpressed in different OC cell lines and may promote the migration and invasion of OC, inhibit its apoptosis and promote the development of OC through the miR-411-3p/HIF-1a/VEGF/p38 pathway. Chen et al. [30] found that the expression of lncRNA PVT1 was upregulated in OC samples. Knockout of lncRNA PVT1 inhibited the proliferation, migration, and invasion of SKOV3 cells. The potential mechanism may be that lncRNA PVT1 caused the combination of Enhancer of zeste homologue 2 (EZH2) and the miR-214 promoter, to inhibit the expression of miR-214, and then promote the progression of OC. Zhang et al. [31] found that the expression of lncRNA HOXD-AS1 was significantly higher in EOC. LncRNA HOXD-AS1 competitively adsorbed miR-133A-3p, activated Wnt/β-Catenin signal pathway, enhanced the proliferation of EOC cells, regulated the EMT process, accelerated tumor metastasis, and ultimately promoted tumor progression. Shang et al. [32] found that the lncRNAs HOTIP, IL-6 and PD-L1 were highly expressed in OC tissues. Their expression levels were positively correlated. Mechanistic studies showed that the lncRNA HOTTIP could promote the secretion of IL-6, upregulate the expression of PD-L1 in neutrophils, and inhibit the activity of T cells, ultimately accelerating the immune escape of ovarian cancer cells and promoting the progression of ovarian cancer.

2.2 Some Other LncRNAs can Inhibit the Occurrence and Development of Ovarian Cancer

LncRNAs have dual effects on OC. Some lncRNAs can promote the occurrence and development of OC, whereas others can inhibit the progress of OC [33, 34, 35, 36, 37, 38]. Sun et al. [39] found that lncRNA EPB41L4A-AS2 was expressed at low levels in OC. The SKOV3 cell line was cultured in vitro and transfected with EPB41L4A-AS2 overexpression plasmid. They found that upregulating the expression of lncRNA EPB41L4A-AS2 could inhibit the proliferation, colony formation, migration, and invasion of SKOV3 cells. In addition, 3–4 weeks old female BALB/c nude mice were injected with transfected SKOV3 cells, and tumor volume was measured and recorded regularly. Animal experiments confirmed that overexpressed lncRNA EPB41L4A-AS2 inhibited the formation of tumors in vivo. Further mechanistic studies have shown that lncRNA EPB41L4A-AS2 can upregulate the expression of the transcription factor RUNX1T1 by binding microrNA-103A, inhibit the progression of OC and play a similar role as tumor suppressor genes. Long et al. [40] discovered low expression of lncRNA GAS5 in EOC tissues and HEY, A2780, A2780/DDP, SKOV3, SKOV3/DDP and other seven cell lines through microarray and qRT-PCR. Compared with sensitive cell lines, the expression of lncRNA GAS5 in cisplatin DDP-resistant OC cell lines decreased more. Cell transfection upregulated the expression of lncRNA GAS5 in HEY and SKOV3 cells. They found that overexpression of lncRNA GAS5 could lead to G0/G1 phase arrest, increase apoptosis of OC cells, and significant enhancement of the sensitivity of OC cells to DDP. Tumorigenicity tests in nude mice showed that after 4 weeks of injection, the tumor size and weight of the mice in the group stably expressing GAS5 were significantly lower than those in the control group, and the sensitivity to DDP was also significantly enhanced. In conclusion, lncRNA GAS5 could inhibit the progression of OC and enhance sensitivity to chemotherapy. Chen et al. [41] detected 40 OC tissues, 40 control samples, ES-2CaOV-3SKOV3 and OVCAR-3 OC cell lines, they found that lncRNA HAND2-AS1 was expressed at low levels in OC. After upregulating the expression of lncRNA HAND2-AS1 by cell transfection, the proliferation rate of tumor cells was significantly inhibited, and the apoptosis rate was enhanced. Tumorigenesis test of xenografts in nude mice also showed that overexpression of lncRNA HAND2-AS1 could inhibit the growth of tumor volume. Gokulnath et al. [42] also found low expression of lncRNA HAND2-AS1 in high-grade serous ovarian cancer (HGSC) in a study of the relationship between lncRNAs and OC. They also confirmed that the downregulation of lncRNA HAND2-AS1 was caused by promoter methylation in HGSC and played a tumor suppressive role in the HGSC cell line. Upregulation of lncRNA HAND2-AS1 expression can improve the sensitivity of HGSC cells to the HDAC inhibitor panobinostat. Wang et al. [43] found that lncRNA XIST was significantly downregulated in EOC cells. LncRNA XIST was stably overexpressed in EOC cells after lentivirus transfection. They found that upregulation of lncRNA XIST could inhibit proliferation, invasion, and tumor growth in vivo, and increase the chemosensitivity of OC cells to cisplatin by reversing the downregulation of HSA-miR-214-3p, thus playing a significant anticancer role. Gokulnath et al. [44] found that the expression of LncRNA MAGI2-AS3 was lower in EOC tissues and cell lines. Further studies showed that lncRNA MAGI2-AS3 could adsorb miR-15-5p, miR-374a-5p, and miR-374b-5p, change the downstream signals of some mRNAs through the ceRNA network, and play a tumor inhibitory role in EOC, especially in HGSC. Fang et al. [45] confirmed that the expression of lncRNA GAS8-AS1 was low in OC tissues, COC1, A2780 and SKOV3 cell lines. The overexpression of lncRNA GAS8-AS1 inhibited the growth of OC cells, whereas the loss of lncRNA GAS8-AS1 promoted the growth of cancer cells. Further mechanistic studies showed that lncRNA GAS8-AS1 inhibited the progression of OC by binding with Beclin1 to activate autophagy (Table 1, Ref. [13, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 37, 38, 39, 40, 41, 43, 44, 45]).

Table 1.Function of LncRNAs in Ovarian Cancer.
LncRNA Experimental models Expression Function Mechanism Refs.
THOR Cell lines, Clinical samples, Mice Up Promote Promote OC cells growth, metastasis and self-renewal by activating IL-6/TAT3 signal [13]
TP73-AS1 Cell lines, Clinical samples, Mice Up Promote Promote OC cells proliferation and metastasis via MMP2 and MMP9 [16]
LINC00858 Cell lines, Clinical samples Up Promote Aggravate the development of OC through miR-134-5p/RAD18 signal [17]
MALAT1 Cell lines, Clinical samples, Mice Up Promote Enhance OC Cell stemness by enhancing YAP translocational activity; promote OC progress through miR-211/PHF19 signal [18, 20]
LINC00176 Cell lines, Clinical samples, Mice Up Promote Promote OC progress by increasing ceruloplasmin expression via BCL3 [19]
ROR Cell lines, Clinical samples Up Promote Promote EMT through the miR-145/FLNB regulatory axis in OC [21]
SRA Cell lines, Clinical samples, Mice Up Promote Promote cell migration, invasion, and progression of OC via NOTCH and EMT [22]
H19 Cell lines Up Promote Promote TGF-β-induced EMT by acting as a ceRNA of miR-370-3p [23]
UCA1 Cell lines, Clinical samples, Mice Up Promote Regulate tumor stem cells and promote EMT [24]
PTAR Cell lines, Clinical samples, Mice Up Promote Promote EMT in SOC through miR-101-3p/ZEB1 signal [25]
RHPN1-AS1 Cell lines, Clinical samples, Mice Up Promote Promote OC progress by combining miR-596 and upregulaing LETM1 [26]
DANCR Cell lines, Clinical samples Up Promote Promote OC progress through negative regulation of UPF1 expression [27]
LBX2-AS1 Cell lines, Clinical samples Mice Up Promote Drive OC progress via the miR-455-5p and miR-491-5p [28]
CDKN2B-AS1 Cell lines, Mice Up Promote Combine with miR-411-3p, promote OC progress through HIF-1a/VEGF/P38 pathway [29]
PVT1 Cell lines, Clinical samples Up Promote Regulate EMT process and interact with EZH2 represses miR-214 expression in OC cells. [30]
HOXD-AS1 Cell lines, Clinical samples Up Promote Promote EOC progress through miR-133a-3p and Wnt/β-Catenin signal pathway [31]
HOTTIP Cell lines, Clinical samples, Mice Up Promote Upregulate the expression of PD-L1 and IL-6, enhance the immune escape of OC cells, and promote tumor progression [32]
SNHG9 Cell lines, Clinical samples Down Inhibit Inhibite OC progress by sponging microRNA-214-5p [33]
NPBWR1-2 Cell lines Down Inhibit Affect the expression of IGFBP7 through miRNA and play an inhibitory role in tumor [34]
LEMD1-AS1 Cell lines, Clinical samples, Mice Down Inhibit Suppress OC progress by sponging miR-183-5p and regulation of TP53 [35]
WDFY3-AS2 Cell lines, Clinical samples, Mice Down Inhibit Inhibite tumor progress by sponging microRNA-18a in OC cells [37]
ASAP1-IT1 Cell lines, Clinical samples Down Inhibit Suppress OC progress by regulating Hippo/YAP signaling [38]
EPB41L4A-AS2 Cell lines, Clinical samples, Mice Down Inhibit Suppress OC progress by adsorbing microRNA-103a and upregulating the expression of RUNX1T1 [39]
GAS5 Cell lines, Clinical samples, Mice Down Inhibit Inhibit tumor progress of EOC via GAS5-E2F4-PARP1-MAPK axis [40]
HAND2-AS1 Cell lines, Clinical samples, Mice Down Inhibit Upregulate expression of BCL2L11 by competitively binding with miR-340-5p, act as a tumor suppressor in OC [41]
XIST Cell lines, Mice Down Inhibit Inhibit EOC progress through hsa-miR-214-3p [43]
MAGI2-AS3 Cell lines Down Inhibit Inhibit OC progress by sponging miR-15-5p, miR-374a-5p and miR-374b-5p [44]
GAS8-AS1 Cell lines, Clinical samples, Mice Down Inhibit Suppress OC progress through activating Beclin1-mediated autophagy [45]
3. Clinical Significance of LncRNAs in Ovarian Cancer
3.1 LncRNA and Diagnosis of Ovarian Cancer

Most OC patients have no typical symptoms at the initial stage and usually are at an advanced stage when diagnosed, having missed the best treatment opportunity and resulting in high mortality. Therefore, effective early diagnosis methods are of great significance for OC [46, 47, 48]. According to relevant literature reports, early detection of OC can reduce mortality by 10%–30% [49]. With the increasing number of studies on lncRNAs, they have been found to be potentially useful as tumor markers for the early diagnosis of OC [50, 51, 52, 53, 54, 55]. Liu et al. [56] examined the expression level of lncRNA LOXL1-AS1 in the serum of 185 patients with EOC and 43 healthy volunteers, and constructed an ROC curve to evaluate diagnostic ability of lncRNA LOXL1-AS1 expression levels in EOC. The result was that the expression level of lncRNA LOXL1-AS1 in the serum of the EOC patients was significantly higher. The area under the ROC curve (AUC) of lncRNA LOXL1-AS1 was 0.843, the 95% confidence interval (CI) was 0.756–0.931, the sensitivity was 63.7%, and the specificity was 85.3%. These findings suggest that the detection of serum lncRNA LOXL1-AS1 expression levels may be helpful for the early diagnosis of EOC patients. In a study of lncRNA-LINC01554 and OC, Luo et al. [57] found that its expression was significantly lower in tumor tissues and can be used for the early diagnosis of OC. The ROC analysis results showed that the AUC value was 0.7827, the 95% CI was 0.7333–0.8322, and the sensitivity and specificity reached 73.32% and 89.67%, respectively. Shen et al. [58] found high expression of lncRNA ROR in OC tissues, and its level was positively correlated with CA125. The combined detection of plasma lncRNA ROR and CA125 has ideal clinical significance for the early diagnosis of OC. Therefore, the lncRNA ROR level can be used for OC diagnosis.

3.2 LncRNA as Therapeutic Targets in Ovarian Cancer

The main therapies for OC are surgery and chemotherapy, supplemented by radiotherapy, targeted therapy, and immunotherapy [59, 60, 61, 62]. The treatment of OC is becoming increasingly advanced with the rapid development of medical technology, but it still faces many difficulties, such as missing the best operation opportunity, chemoresistance, poor radiotherapy sensitivity, and so on [63, 64, 65]. LncRNAs are abnormally expressed in OC and promote or inhibit tumor development. Therefore, lncRNAs are potential therapeutic targets for OC [66, 67, 68, 69, 70, 71, 72]. Liu et al. [73] found that the expression of lncRNA PCA3 in EOC tissues was higher than that in normal ovarian tissues. Overexpression of lncRNA PCA3 can promote the progression of EOC through the miR-106b/RhoC pathway. Knockout of lncRNA PCA3 inhibited cell proliferation and invasion and slowed down tumor progression. Therefore, inhibiting the expression of lncRNA PCA3 may be an effective gene therapeutic strategy for the treatment of OC. Cheng et al. [74] showed that siRNA targeting lncRNA AB073614 can effectively inhibit the growth and metastasis of HO-8910 and OVCAR3 cells, leading to cell arrest in the G1 phase of the cell cycle and promoting apoptosis. Therefore, lncRNA AB073614 can be used as a therapeutic target for OC. A large number of studies have shown that lncRNAs are closely related to chemotherapy resistance and radiotherapy sensitivity in OC [75, 76, 77, 78, 79, 80, 81, 82]. Zhang et al. [83] found cell models that have high expression of lncRNA HOTIAR and low expression of miR-138-5p in SKOV3/DDP and A2780/DDP OC. Knockdown of lncRNA HOTAIR can increase miR-138-5p expression; miR-138-5p can regulate the expression of the cisplatin resistance-related proteins EZH2 and SIRT1, thus improving the sensitivity of cisplatin-resistant cells to cisplatin. The lncRNA HOTAIR/miR-138-5p axis can regulate cisplatin resistance of OC cells through the potential targets EZH2 and SIRT1, which may provide a new therapeutic strategy for OC. Wang et al. [84] found that lncRNA-UCA1 is significantly overexpressed in paclitaxel-resistant OC cells. LncRNA-UCA1 increases the resistance of OC cells to paclitaxel by regulating miR-129/ABCB1. The research team proposed that lncRNA-UCA1/miR-129/ABCB1 could be used as a new regulatory axis of PTX resistance in OC, providing a potential therapeutic target for clinical treatment. Li et al. [85] observed that lncRNA-UCA1 expression was also upregulated in the tissues and cells of cisplatin-resistant patients, and knockout of lncRNA UCA1 inhibited the proliferation of OC cells and promoted cisplatin-induced apoptosis. Mechanistic studies have shown that lncRNA UCA1 can regulate cisplatin resistance in OC through the miR-143/FOSL2 pathway. Yang et al. [86] found that lncRNA CRNDE was highly expressed in the acquired radiotherapy-resistant cell line CAOV3/R. Silencing of lncRNA CRNDE expression by siRNA could significantly enhance the sensitivity of CAOV3/R cells to radiotherapy and inhibit clone formation. In addition, combined with in vivo animal experiments, targeted silencing of lncRNA CRNDE was found to reverse CAOV3/R radiotherapy resistance and inhibit tumor growth. Therefore, they concluded that lncRNA CRNDE could be used as a potential target for OC therapy.

3.3 LncRNAs and Prognosis and Recurrence of Ovarian Cancer

In recent years, with the advancement and diversification of OC therapy, the effects have improved significantly. However, due to the high recurrence rate, the 5-year survival rate is still low. Therefore, screening for reliable prognostic and recurrence markers is of great significance for OC [87, 88, 89]. The clinical application of lncRNAs for OC is not only limited to diagnosis and therapy but can also be used to predict prognosis and recurrence [90, 91, 92, 93, 94, 95, 96]. Chen et al. [97] downloaded OC gene expression data from gene expression database (GEO). Weighted correlation network analysis (WGCNA) and multivariate Cox proportional hazards regression (Cox-PHR) analysis were used to screen prognoses related lncRNAs. Kaplan Meier analysis and Receiver Operating Characteristic (ROC) curve analysis were used to evaluate the prediction ability of selected lncRNAs. Finally, five reliable LncRNAs were identified: LINC01419, LOC286437, LINC01139, LINC00664 and LINC00667. In the test cohort, researchers found that the above LncRNAs were stable in predicting risk of OC recurrence. Multivariate Cox-PHR analysis showed that the above LncRNAs were independent risk factors for OC recurrence and could effectively predict the risk of OC recurrence. Xue et al. [98] detected the expression of lncRNA CASC2 in 126 EOC tissue samples and 5 EOC cell lines (A2780, SKOV3, IGROV-1, OV90 and ES2) by qRT-PCR. The results showed that the expression of lncRNA CASC2 in EOC tissues and cells was lower than in those of the control group. Further analysis showed that low lncRNA CASC2 expression was an independent risk factor for low overall survival rate (HR = 0.417; 95% CI = 0.251–0.693; p = 0.001) and low progression-free survival rate (HR = 0.426; 95% CI = 0.260–0.699; p = 0.001) in EOC patients. LncRNA CASC2 may be a biomarker of poor prognosis in EOC patients. Huang et al. [99] analyzed tissue samples of 109 OCpatients and 4 OC cell lines (SKOV3, OVCAR3, A2780 and IGROV1) by qRT-PCR. The results showed that the lncRNA CCAT2 expression level was high in OC tissues and cells, and it was positively related to Federation International of Gynecology and Obstetrics (FIGO) stage, tumor grade, and distant metastasis. They also found that the overall survival rate and progression-free survival rate of patients with high lncRNA CCAT2 expression were lower than those with low lncRNA CCAT2 expression (p < 0.001). Multivariate analysis showed that lncRNA CCAT2 was an independent factor influencing the poor prognosis of OC patients. Qiu et al. [100] analyzed the expression level of lncRNA ANRIL in 68 serous ovarian cancer (SOC), 30 non cancer tissues and SK-OV-3, HO8910, SK-OV-3.ip1, HO8910-PM cell lines by qRT-PCR. They found that lncRNA-ANRIL expression increased in SOC, which may regulate the progress of SOC cells by regulating MET and MMP3. Knocking out lncRNA ANRIL inhibited migration and invasion of OC cells. The study also found that the overall survival (OS) of SOC patients with high expression of lncRNA ANRIL was shortened, and that lncRNA ANRIL could be used as an independent factor to predict OS of patients with SOC. Thus, lncRNA ANRIL could be a potential marker to predict the recurrence and prognosis of clinical OC patients. Guo et al. [101] constructed a functional lncRNA-mRNA regulatory network (OVLMN) related to malignant progression of OC through a multi-step method. High-throughput molecular profiles of 399 patients with ovarian serous cystadenoma in The Cancer Genome Atlas (TCGA) were used for comprehensive analysis. They found two protective lncRNAs: AC104699.1.1 and RP11-284N8.3.1. They are differentially expressed in OC patients and could activate the immune system response, which is significantly related to patient survival and disease stage. Integrating them into the OC risk model can divide patients into different risk groups and predict their survival rate. Hong et al. [102] detected the expression level of lncRNA SNHG3 in 76 human OC tissue samples and A2780, SKOV3, ES2 and OVCAR3 OC cell lines by qRT-PCR. The results showed that the expression level of lncRNA SNHG3 was higher in OC tissues and cells than in control samples, and the expression level was positively correlated with FIGO stage and lymph node metastasis of OC patients. Univariate and multivariate Cox regression analyses showed that high expression of the lncRNA SNHG3 could be an independent prognostic factor for the overall survival rate of OC patients (Table 2, Ref. [51, 54, 56, 57, 58, 66, 68, 70, 72, 73, 74, 75, 76, 79, 81, 83, 85, 86, 91, 95, 97, 98, 99, 100, 101, 102]).

Table 2.Clinical application of lncRNAs in ovarian cancer.
LncRNA OC type Expression Number of patients Clinical application (Diagnosis/Therapy/Prognosis) Refs.
HAGLROS OC Up 41 Early diagnosis and prognostic evaluation for OC—Diagnostic biomarker and factor associated with survival [51]
FLJ33360 OC Down 32 Participate in OC progression target miR-30b-3p—Diagnostic biomarker and factor associated with survival [54]
LOXL1-AS1 EOC Up 185 Early diagnosis and prognostic evaluation for EOC—Diagnostic biomarker and factor associated with survival [56]
LINC01554 EOC Down 161 Diagnostic biomarker, therapeutic target and factor associated with survival [57]
ROR OC Up 60 Early diagnosis of OC—Diagnostic biomarker [58]
NEAT1 OC Up 32 Promote the resistance of OC to PTX by regulating EMT—Therapeutic target [66]
CCAT1 EOC Up N/A (cell lines, mice) Promote chemoresistance of OC cells to cisplatin by sponging miR-454—Therapeutic target and factor associated with survival [68]
TUG1 OC Up N/A (cell lines) Inhibit tumor angiogenesis in OC by regulating LRG1—Diagnostic biomarker and therapeutic target [70]
CHRF OC Up 20 Promote the resistance of OC to cisplatin resistance—Therapeutic target [72]
PCA3 EOC Up 36 Treat OC by inhibiting PCA3 expression—Therapeutic target [73]
AB073614 OC Up 75 Inhibit OC through SiRNA targeting lncRNA AB073614—Therapeutic target [74]
NEAT1 OC Up 32 Enhance paclitaxel (PTX) resistance of OC—Therapeutic target [75]
ANRIL EOC Up 86 (EOC) Affect the sensitivity of EOC to cisplatin—Therapeutic target; Predict poor prognosis of SOC—Factor associated with survival [76, 100]
SOC 68 (SOC)
LINC01125 OC Down 21 Enhance the cisplatin sensitivity of OC cells by binding to miR-1972—Therapeutic target [79]
FAM83H-AS1 OC UP 80 Enhance radioresistance, guide clinical treatment—Therapeutic target [81]
HOTAIR OC Up N/A (cell lines) Reverse cisplatin resistance of OC cells through knockdown of HOTAIR—Therapeutic target [83]
UCA1 OC UP 56 Reverse the tolerance of OC to chemotherapeutic drugs—Therapeutic target [85]
CRNDE OC Up N/A (cell lines, mice) Reverse radiotherapy resistance of OC Cell Strain CAOV3/R by Targeting LncRNA CRNDE—Therapeutic target [86]
CCEPR OC Up N/A (cell lines) Predict the poor prognosis of OC patients—Factor associated with survival [91]
SNHG20 EOC Up 60 Serve as an independent prognostic predictor in EOC—Factor associated with survival [95]
LINC00664 OC Up N/A (Bioinformatics) Independent risk factors for OC recurrence—Factor associated with survival [97]
LINC00667 OC Up N/A (Bioinformatics) Independent risk factors for OC recurrence—Factor associated with survival [97]
LINC01139 OC Up N/A (Bioinformatics) Independent risk factors for OC recurrence—Factor associated with survival [97]
LINC01419 OC Up N/A (Bioinformatics) Independent risk factors for OC recurrence—Factor associated with survival [97]
LOC286437 OC Up N/A (Bioinformatics) Independent risk factors for OC recurrence—Factor associated with survival [97]
CASC2 EOC Down 126 Inhibit progression and predicts favorable prognosis in EOC—Therapeutic target and factor associated with survival [98]
CCAT2 OC Up 109 Potential prognostic biomarker and therapeutic target for patients with OC [99]
RP11-284N8.3.1 OC Up 399 Biomarker for the prognosis of patients—Factor associated with survival [101]
AC104699.1.1 OC Up 399 Biomarker for the prognosis of patients—Factor associated with survival [101]
SNHG3 OC Up 76 Poor prognosis enhancing malignant progression of OC—Factor associated with survival [102]

OC, ovarian cancer; EOC, epithelial ovarian cancer; SOC, serous ovarian cancer.
4. Discussion

With the increase in research of lncRNAs, more and more lncRNAs have been proven to be potential biomarkers and targets for the diagnosis and treatment of OC. In particular, some lncRNAs can participate in regulating the occurrence and development of OC in various ways, showing great potential in clinical diagnosis and treatment of OC. LncRNA TUG1 is one of them. lncRNA TUG1 is a newly discovered tumor-related lncRNA. Many studies have shown that the expression of lncRNA TUG1 is up-regulated in OC tissues and cells, and can participate in the occurrence and development, regulate the apoptosis, autophagy, and other processes of OC through multiple pathways such as lncRNA TUG1/miR-186-5p/ZEB1, lncRNA TUG1/miR-29b-3p/MDM2, lncRNA TUG1/miR-1299/NOTCH3, lncRNA TUG1/miR-582-3p/AKT/mTR. In addition, they are closely related to the cancer grading, FIGO staging, metastasis, chemotherapy resistance, and efficacy evaluation of OC [103, 104, 105, 106, 107]. It is noteworthy that recent studies have shown that lncRNA TUG1 can also be targeted by the effective components of Traditional Chinese Medicine. For example, polydatin, the effective component of polygonum cuspidatum, can improve the sensitivity of OC cells to the chemotherapy drug Doxorubicin by reducing the expression of TUG1 [108]. Our research team is deeply interested in the research of lncRNAs and OC, and has studied Traditional Chinese Medicine and cancer for many years. We will continue to study this, and strive to find new potential targets for the treatment of OC.

More and more lncRNAs have been confirmed to be closely related to OC. However, due to the short period of understanding of lncRNAs, research on the relationship between lncRNAs and OC still faces many problems, such as the following: (a) only a few lncRNAs have been identified for their functions and target genes; (b) lncRNA research and detection methods need to be further improved; and (c) lncRNAs and their target genes form a complex regulatory network. Therefore, it is also a complex research process to clarify which lncRNA plays a role in OC cells through which pathway. Although the research in this field faces many difficulties, it still attracts many research scholars. With the continuous expansion of medical knowledge and the progress of research methods, we believe that lncRNAs will scientifically and effectively guide the early diagnosis, therapy and efficacy prediction of OC.

Author Contributions

LZ—analyze literature and write the paper; XL, YW, BL—collect and sort out literatures; YZ and XD—revise and review the paper. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Ethics Approval and Consent to Participate

Not applicable.

Acknowledgment

We acknowledge the Second Hospital of Jilin University for its administrative and technical support.

Funding

This work was supported by Special Health Project of Jilin Province (No. 2020SCZT061, No. 2019SCZT026); Bethune Project (No. 419161900018); International science and technology cooperation project of Jilin Province (20210402003GH); Natural Science of Science and Technology Division Jilin (20200201505JC); Jilin Provincial Science and Technology Development Project (20200201577JC).

Conflict of Interest

The authors declare no conflict of interest.

References
[1]
Bridges MC, Daulagala AC, Kourtidis A. LNCcation: lncRNA localization and function. The Journal of Cell Biology. 2021; 220: e202009045.
[2]
Zhang X, Wang W, Zhu W, Dong J, Cheng Y, Yin Z, et al. Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels. International Journal of Molecular Sciences. 2019; 20: 5573.
[3]
Bunch H. Gene regulation of mammalian long non-coding RNA. Molecular Genetics and Genomics. 2018; 293: 1–15.
[4]
Gardini A, Shiekhattar R. The many faces of long noncoding RNAs. The FEBS Journal. 2015; 282: 1647–1657.
[5]
Graf J, Kretz M. From structure to function: Route to understanding lncRNA mechanism. BioEssays. 2020; 42: e2000027.
[6]
Kondo Y, Shinjo K, Katsushima K. Long non-coding RNAs as an epigenetic regulator in human cancers. Cancer Science. 2017; 108: 1927–1933.
[7]
Muñoz-Galván S, Carnero A. Targeting Cancer Stem Cells to Overcome Therapy Resistance in Ovarian Cancer. Cells. 2020; 9: 1402.
[8]
Penny SM. Ovarian Cancer: An Overview. Radiologic Technology. 2020; 91: 561–575.
[9]
Rahimian N, Razavi ZS, Aslanbeigi F, Mirkhabbaz AM, Piroozmand H, Shahrzad MK, et al. Non-coding RNAs related to angiogenesis in gynecological cancer. Gynecologic Oncology. 2021; 161: 896–912.
[10]
Zhan L, Li J, Wei B. Long non-coding RNAs in ovarian cancer. Journal of Experimental & Clinical Cancer Research. 2018; 37: 120.
[11]
Oncul S, Amero P, Rodriguez-Aguayo C, Calin GA, Sood AK, Lopez-Berestein G. Long non-coding RNAs in ovarian cancer: expression profile and functional spectrum. RNA Biology. 2020; 17: 1523–1534.
[12]
Wang JY, Lu AQ, Chen LJ. LncRNAs in ovarian cancer. Clinica Chimica Acta. 2019; 490: 17–27.
[13]
Ge J, Han T, Shan L, Na J, Li Y, Wang J. Long non-coding RNA THOR promotes ovarian Cancer cells progression via IL-6/STAT3 pathway. Journal of Ovarian Research. 2020; 13: 72.
[14]
Hashemipour M, Boroumand H, Mollazadeh S, Tajiknia V, Nourollahzadeh Z, Rohani Borj M, et al. Exosomal microRNAs and exosomal long non-coding RNAs in gynecologic cancers. Gynecologic Oncology. 2021; 161: 314–327.
[15]
Qu J, Kamal MA, Yuan C. The Regulatory Roles of Long Non-Coding RNA in the Chemoresistance Process of Ovarian cancer. Current Pharmaceutical Design. 2019; 25: 856–861.
[16]
Wang X, Yang B, She Y, Ye Y. The lncRNA TP73-AS1 promotes ovarian cancer cell proliferation and metastasis via modulation of MMP2 and MMP9. Journal of Cellular Biochemistry. 2018; 119: 7790–7799.
[17]
Xue H, Wu Z, Rao D, Zhuo B, Chen Q. Long non-coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR-134-5p/RAD18 signaling. Archives of Gynecology and Obstetrics. 2020; 302: 1243–1254.
[18]
Wu X, Wang Y, Zhong W, Cheng H, Tian Z. The Long Non-Coding RNA MALAT1 Enhances Ovarian Cancer Cell Stemness by Inhibiting YAP Translocation from Nucleus to Cytoplasm. Medical Science Monitor. 2020; 26: e922012.
[19]
Dai L, Niu J, Feng Y. Knockdown of long non-coding RNA LINC00176 suppresses ovarian cancer progression by BCL3-mediated down-regulation of ceruloplasmin. Journal of Cellular and Molecular Medicine. 2020; 24: 202–213.
[20]
Tao F, Tian X, Ruan S, Shen M, Zhang Z. miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma. FASEB Journal. 2018. (online ahead of print)
[21]
Li J, Zhang S, Wu L, Pei M. Interaction between LncRNA-ROR and miR-145 contributes to epithelial-mesenchymal transition of ovarian cancer cells. General Physiology and Biophysics. 2019; 38: 461–471.
[22]
Kim LK, Park SA, Yang Y, Kim YT, Heo TH, Kim HJ. LncRNA SRA mediates cell migration, invasion, and progression of ovarian cancer via NOTCH signaling and epithelial-mesenchymal transition. Bioscience Reports. 2021; 41: BSR20210565.
[23]
Li J, Huang Y, Deng X, Luo M, Wang X, Hu H, et al. Long noncoding RNA H19 promotes transforming growth factor-β-induced epithelial-mesenchymal transition by acting as a competing endogenous RNA of miR-370-3p in ovarian cancer cells. OncoTargets and Therapy. 2018; 11: 427–440.
[24]
Hosseini NF, Manoochehri H, Khoei SG, Sheykhhasan M. The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study. Current Molecular Medicine. 2021; 21: 96–110.
[25]
Liang H, Yu T, Han Y, Jiang H, Wang CY, You TY, et al. LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression. Molecular Cancer. 2018; 17: 119.
[26]
Wang J, Ding W, Xu Y, Tao E, Mo M, Xu W, et al. Long non-coding RNA RHPN1-AS1 promotes tumorigenesis and metastasis of ovarian cancer by acting as a ceRNA against miR-596 and upregulating LETM1. Aging. 2020; 12: 4558–4572.
[27]
Pei CL, Fei KL, Yuan XY, Gong XJ. LncRNA DANCR aggravates the progression of ovarian cancer by downregulating UPF1. European Review for Medical and Pharmacological Sciences. 2019; 23: 10657–10663.
[28]
Cao J, Wang H, Liu G, Tang R, Ding Y, Xu P, et al. LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging. Journal of Cellular and Molecular Medicine. 2021; 25: 1178–1189.
[29]
Wang Y, Huang Y, Liu H, Su D, Luo FY, Zhou F. Long noncoding RNA CDKN2B-AS1 interacts with miR-411-3p to regulate ovarian cancer in vitro and in vivo through HIF-1a/VEGF/P38 pathway. Biochemical and Biophysical Research Communications. 2019; 514: 44–50.
[30]
Chen Y, Du H, Bao L, Liu W. LncRNA PVT1 promotes ovarian cancer progression by silencing miR-214. Cancer Biology & Medicine. 2018; 15: 238–250.
[31]
Zhang Y, Dun Y, Zhou S, Huang XH. LncRNA HOXD-AS1 promotes epithelial ovarian cancer cells proliferation and invasion by targeting miR-133a-3p and activating Wnt/β-catenin signaling pathway. Biomedicine and Pharmacotherapy. 2017; 96: 1216–1221.
[32]
Shang A, Wang W, Gu C, Chen C, Zeng BJ, Yang YB, et al. Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils. Journal of Experimental & Clinical Cancer Research. 2019; 38: 411.
[33]
Chen GY, Zhang ZS, Chen Y, Li, Y. Long non-coding RNA SNHG9 inhibits ovarian cancer progression by sponging microRNA-214-5p. Oncology Letters. 2021; 21: 80.
[34]
Liu S, Du Q, Rao Y, Liu C, Qu P. Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs. Oncology Letters. 2020; 20: 685–692.
[35]
Guo R, Qin Y. LEMD1-AS1 Suppresses Ovarian Cancer Progression Through Regulating miR-183-5p/TP53 Axis. OncoTargets and Therapy. 2020; 13: 7387–7398.
[36]
Filippov-Levy N, Davidson B, Reich R. The Biological Role of the Long Non-coding RNA LINK-A in Ovarian Carcinoma. Anticancer Research. 2020; 40: 6677–6684.
[37]
Li W, Ma S, Bai X, Pan W, Ai L, Tan W. Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer. Journal of Cellular Physiology. 2020; 235: 1141–1154.
[38]
Wang K, Hu YB, Zhao Y, Ye C. Long non‑coding RNA ASAP1‑IT1 suppresses ovarian cancer progression by regulating Hippo/YAP signaling. International Journal of Molecular Medicine. 2021; 47: 44.
[39]
Sun T, Yang P, Gao Y. Long non-coding RNA EPB41L4A-AS2 suppresses progression of ovarian cancer by sequestering microRNA-103a to upregulate transcription factor RUNX1T1. Experimental Physiology. 2020; 105: 75–87.
[40]
Long X, Song K, Hu H, Tian Q, Wang W, Dong Q, et al. Long non-coding RNA GAS5 inhibits DDP-resistance and tumor progression of epithelial ovarian cancer via GAS5-E2F4-PARP1-MAPK axis. Journal of Experimental & Clinical Cancer Research. 2019; 38: 345.
[41]
Chen J, Lin Y, Jia Y, Xu TM, Wu F, Jin Y. LncRNA HAND2-AS1 exerts anti-oncogenic effects on ovarian cancer via restoration of BCL2L11 as a sponge of microRNA-340-5p. Journal of Cellular Physiology. 2019; 234: 23421–23436.
[42]
Gokulnath P, de Cristofaro T, Manipur I, Di Palma T, Soriano AA, Guarracino MR, et al. Long Non-Coding RNA HAND2-AS1 Acts as a Tumor Suppressor in High-Grade Serous Ovarian Carcinoma. International Journal of Molecular Sciences. 2020; 21: 4059.
[43]
Wang C, Qi S, Xie C, Li C, Wang P, Liu D. Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p. Journal of Gynecologic Oncology. 2018; 29: e99.
[44]
Gokulnath P, de Cristofaro T, Manipur I, Di Palma T, Soriano AA, Guarracino MR, et al. Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma. Cancers. 2019; 11: 2008.
[45]
Fang YJ, Jiang P, Zhai H, Dong JS. LncRNA GAS8-AS1 Inhibits Ovarian Cancer Progression Through Activating Beclin1-Mediated Autophagy. OncoTargets and Therapy. 2020; 13: 10431–10440.
[46]
Chandra A, Pius C, Nabeel M, Nair M, Vishwanatha JK, Ahmad S, et al. Ovarian cancer: Current status and strategies for improving therapeutic outcomes. Cancer Medicine. 2019; 8: 7018–7031.
[47]
Bonifácio VDB. Ovarian Cancer Biomarkers: Moving Forward in Early Detection. Advances in Experimental Medicine and Biology. 2020; 1219: 355–363.
[48]
Mathis J, Jellouli MA, Sabiani L, Fest J, Blache G, Mathevet P. Ovarian cancer screening in the general population. Hormone Molecular Biology and Clinical Investigation. 2019; 41.
[49]
Elias KM, Guo J, Bast RC Jr. Early Detection of Ovarian Cancer. Hematology/Oncology Clinics of North America. 2018; 32: 903–914.
[50]
Salamini-Montemurri M, Lamas-Maceiras M, Barreiro-Alonso A, Vizoso-Vázquez Á, Rodríguez-Belmonte E, Quindós-Varela M, et al. The Challenges and Opportunities of LncRNAs in Ovarian Cancer Research and Clinical Use. Cancers. 2020; 12: 1020.
[51]
Yang M, Zhai Z, Zhang Y, Wang Y. Clinical significance and oncogene function of long noncoding RNA HAGLROS overexpression in ovarian cancer. Archives of Gynecology and Obstetrics. 2019; 300: 703–710.
[52]
Fu LL, Li CJ, Xu Y, Li LY, Zhou X, Li DD, et al. Role of lncRNAs as Novel Biomarkers and Therapeutic Targets in Ovarian Cancer. Critical Reviews in Eukaryotic Gene Expression. 2017; 27: 183–195.
[53]
Zhang L, Hu C, Huang Z, Li ZJ, Zhang Q, He Y. In Silico screening of circulating tumor DNA, circulating microRNAs, and long non-coding RNAs as diagnostic molecular biomarkers in ovarian cancer: A comprehensive meta-analysis. PLoS ONE. 2021; 16: e0250717.
[54]
Yang M, Zhai Z, Guo S, Li X, Zhu Y, Wang Y. Long non-coding RNA FLJ33360 participates in ovarian cancer progression by sponging miR-30b-3p. OncoTargets and Therapy. 2019; 12: 4469–4480.
[55]
Lou Y, Jiang H, Cui Z, Wang X, Wang L, Han Y. Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer. International Journal of Molecular Medicine. 2018; 42: 91–104.
[56]
Liu CN, Zhang HY. Serum lncRNA LOXL1-AS1 is a diagnostic and prognostic marker for epithelial ovarian cancer. The Journal of Gene Medicine. 2020; 22: e3233.
[57]
Luo T, Jiang Y, Yang J. Long Noncoding RNA LINC01554 as a Novel Biomarker for Diagnosis and Prognosis Prediction of Epithelial Ovarian Cancer. Disease Markers. 2021; 2021: 1244612.
[58]
Shen W, Xie X, Liu M, Wang L. Diagnostic Value of lncRNA ROR in Differentiating Ovarian Cancer Patients. Clinical Laboratory. 2020; 66.
[59]
Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemotherapy and Pharmacology. 2018; 81: 17–38.
[60]
Guan LY, Lu Y. New developments in molecular targeted therapy of ovarian cancer. Discovery Medicine. 2018; 26: 219–229.
[61]
Odunsi K. Immunotherapy in ovarian cancer. Annals of Oncology. 2017; 28: viii1–viii7.
[62]
Herrera FG, Irving M, Kandalaft LE, Coukos G. Rational combinations of immunotherapy with radiotherapy in ovarian cancer. The Lancet Oncology. 2019; 20: e417–e433.
[63]
Tsibulak I, Zeimet AG, Marth C. Hopes and failures in front-line ovarian cancer therapy. Critical Reviews in Oncology/Hematology. 2019; 143: 14–19.
[64]
van Zyl B, Tang D, Bowden NA. Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment. Endocrine-Related Cancer. 2018; 25: R303–R318.
[65]
Orr B, Edwards RP. Diagnosis and Treatment of Ovarian Cancer. Hematology/Oncology Clinics of North America. 2018; 32: 943–964.
[66]
Peng Y, Tang D, Zhao M, Kajiyama H, Kikkawa F, Kondo Y. Long non-coding RNA: A recently accentuated molecule in chemoresistance in cancer. Cancer Metastasis Reviews. 2020; 39: 825–835.
[67]
Worku T, Bhattarai D, Ayers D, Wang K, Wang C, Rehman ZU, et al. Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer. Cellular Physiology and Biochemistry. 2017; 44: 948–966.
[68]
Wang DY, Li N, Cui YL. Long Non-coding RNA CCAT1 Sponges miR-454 to Promote Chemoresistance of Ovarian Cancer Cells to Cisplatin by Regulation of Surviving. Cancer Research and Treatment. 2020; 52: 798–814.
[69]
Bhardwaj V, Tan YQ, Wu MM, Ma L, Zhu T, Lobie PE, et al. Long non-coding RNAs in recurrent ovarian cancer: Theranostic perspectives. Cancer Letters. 2021; 502: 97–107.
[70]
Fan M, Li C, He P, Fu Y, Li M, Zhao X. Knockdown of long noncoding RNA-taurine-upregulated gene 1 inhibits tumor angiogenesis in ovarian cancer by regulating leucine-rich α-2-glycoprotein-1. Anti-Cancer Drugs. 2019; 30: 562–570.
[71]
Li N, Zhan X. Identification of clinical trait-related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer. The EPMA Journal. 2019; 10: 273–290.
[72]
Tan WX, Sun G, Shangguan MY, Gui Z, Bao Y, Li YF, et al. Novel role of lncRNA CHRF in cisplatin resistance of ovarian cancer is mediated by miR-10b induced EMT and STAT3 signaling. Scientific Reports. 2020; 10: 14768.
[73]
Liu Y, Zong ZH, Guan X, Wang LL, Zhao Y. The role of long non-coding RNA PCA3 in epithelial ovarian carcinoma tumorigenesis and progression. Gene. 2017; 633: 42–47.
[74]
Cheng Z, Guo J, Chen L, Luo N, Yang W, Qu X. A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer. Oncotarget. 2015; 6: 25381–25389.
[75]
An J, Lv W, Zhang Y. LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194. OncoTargets and Therapy. 2017; 10: 5377–5390.
[76]
Miao JT, Gao JH, Chen YQ, Chen H, Meng HY, Lou G. LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis. Bioscience Reports. 2019; 39: BSR20182101.
[77]
Li Q, Zhang J, Zhou J, Yang BL, Liu PP, Cao L, et al. lncRNAs are novel biomarkers for differentiating between cisplatin-resistant and cisplatin-sensitive ovarian cancer. Oncology Letters. 2018; 15: 8363–8370.
[78]
Abildgaard C, Do Canto LM, Steffensen KD, Rogatto SR. Long Non-coding RNAs Involved in Resistance to Chemotherapy in Ovarian Cancer. Frontiers in Oncology. 2020; 9: 1549.
[79]
Guo J, Pan H. Long Noncoding RNA LINC01125 Enhances Cisplatin Sensitivity of Ovarian Cancer via miR-1972. Medical Science Monitor. 2019; 25: 9844–9854.
[80]
Wambecke A, Ahmad M, Lambert B, Joly F, Poulain L, Denoyelle C, et al. The influence of long non-coding RNAs on the response to chemotherapy in ovarian cancer. Gynecologic Oncology. 2020; 156: 726–733.
[81]
Dou Q, Xu Y, Zhu Y, Hu Y, Yan Y, Yan H. LncRNA FAM83H-AS1 contributes to the radioresistance, proliferation, and metastasis in ovarian cancer through stabilizing HuR protein. European Journal of Pharmacology. 2019; 852: 134–141.
[82]
Li S, Yao W, Liu R, Gao L, Lu Y, Zhang H, et al. Long non-coding RNA LINC00152 in cancer: Roles, mechanisms, and chemotherapy and radiotherapy resistance. Frontiers in Oncology. 2022; 12: 960193.
[83]
Zhang Y, Ai H, Fan X, Chen S, Wang Y, Liu L. Knockdown of long non-coding RNA HOTAIR reverses cisplatin resistance of ovarian cancer cells through inhibiting miR-138-5p-regulated EZH2 and SIRT1. Biological Research. 2020; 53: 18.
[84]
Wang J, Ye C, Liu J, Hu Y. UCA1 confers paclitaxel resistance to ovarian cancer through miR-129/ABCB1 axis. Biochemical and Biophysical Research Communications. 2018; 501: 1034–1040.
[85]
Li Z, Niu H, Qin Q, Yang S, Wang Q, Yu C, et al. lncRNA UCA1 Mediates Resistance to Cisplatin by Regulating the miR-143/FOSL2-Signaling Pathway in Ovarian Cancer. Molecular Therapy Nucleic Acids. 2019; 17: 92–101.
[86]
Yang W, Li X, Zhao L, Zhao F. Reversal of Radiotherapy Resistance of Ovarian Cancer Cell Strain CAOV3/R by Targeting lncRNA CRNDE. Journal of Healthcare Engineering. 2021; 2021: 8556965.
[87]
Pignata S, C Cecere S, Du Bois A, Harter P, Heitz F. Treatment of recurrent ovarian cancer. Annals of Oncology. 2017; 28: viii51–viii56.
[88]
Kim SI, Lee EJ, Lee M, Chung H, Kim JW, Park NH, et al. Recurrence patterns after bevacizumab in platinum-sensitive, recurrent epithelial ovarian cancer. International Journal of Gynecological Cancer. 2020; 30: 1943–1950.
[89]
Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review. Seminars in Oncology Nursing. 2019; 35: 151–156.
[90]
Nikpayam E, Tasharrofi B, Sarrafzadeh S, Ghafouri-Fard S. The Role of Long Non-Coding RNAs in Ovarian Cancer. Iranian Biomedical Journal. 2017; 21: 3–15.
[91]
Chen Z, Zhu Y, Fan X, Liu Y, Feng Q. Upregulation of long non-coding RNA CCEPR is associated with poor prognosis and contributes to the progression of ovarian cancer through regulating the Wnt/β‑catenin signaling pathway. Molecular Medicine Reports. 2020; 21: 1950–1958.
[92]
Chen M, Lei N, Tian W, Li Y, Chang L. Recent advances of non-coding RNAs in ovarian cancer prognosis and therapeutics. Therapeutic Advances in Medical Oncology. 2022; 14: 17588359221118010.
[93]
Zhao S, Zhu H, Jiao R, Wu X, Ji G, Zhang X. Prognostic and clinicopathological significance of SNHG6 in human cancers: a meta-analysis. BMC Cancer. 2020; 20: 77.
[94]
Zheng M, Hu Y, Gou R, Nie X, Li X, Liu J, et al. Identification three LncRNA prognostic signature of ovarian cancer based on genome-wide copy number variation. Biomedicine and Pharmacotherapy. 2020; 124: 109810.
[95]
Wang D, Dai J, Hou S, Qian Y. LncRNA SNHG20 predicts a poor prognosis and promotes cell progression in epithelial ovarian cancer. Bioscience Reports. 2019; 39: BSR20182186.
[96]
Wang X, Han L, Zhou L, Wang L, Zhang L. Prediction of candidate RNA signatures for recurrent ovarian cancer prognosis by the construction of an integrated competing endogenous RNA network. Oncology Reports. 2018; 40: 2659–2673.
[97]
Chen Y, Bi F, An Y, Yang Q. Identification of pathological grade and prognosis-associated lncRNA for ovarian cancer. Journal of Cellular Biochemistry. 2019; 120: 14444–14454.
[98]
Xue Z, Zhu X, Teng Y. Long non-coding RNA CASC2 inhibits progression and predicts favorable prognosis in epithelial ovarian cancer. Molecular Medicine Reports. 2018; 18: 5173–5181.
[99]
Huang S, Qing C, Huang Z, Zhu Y. The long non-coding RNA CCAT2 is up-regulated in ovarian cancer and associated with poor prognosis. Diagnostic Pathology. 2016; 11: 49.
[100]
Qiu JJ, Lin YY, Ding JX, Feng WW, Jin HY, Hua KQ. Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer. International Journal of Oncology. 2015; 46: 2497–2505.
[101]
Guo Q, Cheng Y, Liang T, He Y, Ren C, Sun L, et al. Comprehensive analysis of lncRNA-mRNA co-expression patterns identifies immune-associated lncRNA biomarkers in ovarian cancer malignant progression. Scientific Reports. 2015; 5: 17683.
[102]
Hong L, Chen W, Wu D, Wang Y. Upregulation of SNHG3 expression associated with poor prognosis and enhances malignant progression of ovarian cancer. Cancer Biomarkers. 2018; 22: 367–374.
[103]
Braga EA, Fridman MV, Moscovtsev AA, Filippova EA, Dmitriev AA, Kushlinskii NE. LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms. International Journal of Molecular Sciences. 2020; 21: 8855.
[104]
Zhan F, Chen C, Yao M. LncRNA TUG1 facilitates proliferation, invasion and stemness of ovarian cancer cell via miR-186-5p/ZEB1 axis. Cell Biochemistry and Function. 2020; 38: 1069–1078.
[105]
Pei Y, Li K, Lou X, Wu Y, Dong X, Wang W, et al. miR‑1299/NOTCH3/TUG1 feedback loop contributes to the malignant proliferation of ovarian cancer. Oncology Reports. 2020; 44: 438–448.
[106]
Gu L, Li Q, Liu H, Lu X, Zhu M. Long Noncoding RNA TUG1 Promotes Autophagy-Associated Paclitaxel Resistance by Sponging miR-29b-3p in Ovarian Cancer Cells. OncoTargets and Therapy. 2020; 13: 2007–2019.
[107]
Dai T, Liang J, Liu W, Zou Y, Niu F, Li M, et al. The miRNA mir-582-3p suppresses ovarian cancer progression by targeting AKT/MTOR signaling via lncRNA TUG1. Bioengineered. 2021; 12: 10771–10781.
[108]
Ashrafizaveh S, Ashrafizadeh M, Zarrabi A, Husmandi K, Zabolian A, Shahinozzaman M, et al. Long non-coding RNAs in the doxorubicin resistance of cancer cells. Cancer Letters. 2021; 508: 104–114.

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