IMR Press / FBL / Volume 24 / Issue 4 / DOI: 10.2741/4749
Open Access Review
Recent advances in the regulation of testicular germ cell tumors by microRNAs
Show Less
1 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
2 University of Chinese Academy of Sciences, Beijing, 100049, China
3 Changsha Reproductive Medicine Hospital, Hunan, Changsha, 410205, China
4 Reproductive Medicine Center of People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
5 Reproduction Medical Center, Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China
*Correspondence: (Su-Ren Chen)
Front. Biosci. (Landmark Ed) 2019, 24(4), 765–776;
Published: 1 March 2019
(This article belongs to the Special Issue Advances in mammalian reproduction)

Testicular germ cell tumors (TGCTs) are generally rare but represent the most common solid tumors in young men. They are classified broadly into seminoma, which resemble primordial germ cells (PGCs), and non-seminoma, which are either undifferentiated (embryonic carcinoma) or differentiated (teratoma, yolk sac tumor, choriocarcinomas) patterning. A widespread role for microRNAs (miRNAs), in diverse molecular processes driving initiation and progression of various types of TGCTs has been recently studied. We discuss the involvement of different miRNAs in the development and progression of different types of TGCTs. Moreover, we highlight the aberrant expression of miRNAs in TGCTs and several targets, which may define miRNAs as oncomiRs or tumor suppressors. A better understanding of miRNA biology may ultimately yield further insight into the molecular mechanisms of tumorigenesis and new therapeutic strategies against TGCTs.

Tumor suppressor

Testicular cancers are generally grouped into three broad categories with type I testicular germ cell tumors (TGCTs) being observed primarily in neonatal boys and young children (1). Type III TGCTs, also called spermatocytic seminomas, affect older men above 50 years of age and are derived from a slowly growing expansion of type B spermatogonia (2). In clinical practice, type II TGCTs are classified as seminomas and non-seminomatous tumors. Non- seminomatous tumors often contain multiple varieties of cell types and can be further sub-divided according to the histological and cellular phenotype in embryonic carcinomas (EC), choriocarcinomas (CC), yolk sac tumors (YST) and teratomas (TT). All type II TGCTs develop from a pre-invasive lesion termed carcinoma in situ (CIS), which has been identified as a dysfunctional fetal germ cell (Figure 1) (2, 3). In the developed world, the incidence of type II TGCTs, but not type I or III, has increased significantly over the last century to become the most common malignancy found in men aged between 20 and 40 years (46). Such findings have led to speculation that environmental factors impact on the tumorigenesis of this cancer (7). The apparent association of TGCTs with infertility raises the possibility that TGCTs may act as indicators of a general reduction in male reproductive health and rising fertility problems within the male population. Moreover, pre-existing sub-fertility increases in patients with type II tumors (89). Type II TGCTs are known to develop from dysfunctional gonocytes located within the seminiferous tubules (10), indicating that the risk factors predisposing an individual to TGCTs stays active in the early male fetal development, necessitating the investigation of early germ cell development in an effort to identify causative factors for type II TGCTs (Figure 1).

Figure 1

Histologically TGCTs are classified as Type I (neonatal boys and young children), Type II (20~40 years old men) & Type III (>50 years old men). Recent studies indicate maintained pluripotency combined with incomplete premature differentiation of gonocytes causes the specification of carcinoma in situ (CIS) cells. Signals caused by puberty make these cells to proliferate and once additional mutations accumulate CIS cells differentiate into type II TGCTs (56). Type II TGCTs are further classified as Seminoma and Non-Seminoma include: Embryonic carcinoma (EC), Choriocarcinoma (CC), yolk-sac tumors (YST) and teratoma (TT).

For the clinical management of TGCTs, increased levels of blood-based markers such as lactate dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin are essential tools for diagnosis, risk assessment and patient’s prognosis (11, 12). However, only 60% of patients with TGCTs show increased serum levels of these tumor markers (13). This proportion of patients is even lower for those with seminomas or pure EC as alpha-fetoprotein is predominantly related to YST and human chorionic gonadotropin to CC. Consequently, alternative and more operative markers should be investigated and introduced into TGCTs’ prognostic and diagnostic field.

Accordingly recent evidence indicates that small non-coding RNA molecules include miRNAs, might also function as tumor suppressors and oncomiRs (oncogenes). miRNAs are an abundant class of endogenous small RNA molecules, 20–25 nucleotides in length (1416), which regulate protein expression by mRNA cleavage or translation repression (15). A large quantity of miRNAs has been identified and subsequent studies indicated that they serve crucial roles in various biological processes and regulate the expression up to 30% of human genes (17, 18). In addition, expression profiling of miRNAs can also be used to distinguish as well as for differentiation of the major histological subtypes of TGCTs (19, 20, 21). As a result of their high sensitivity and the relatively easy method of detection, miRNAs have been shown to exhibit great potential as novel biomarkers for diagnosis, prognosis and therapy in cancer (20).

There have been attempts to use miRNAs as predictive factors for pharmacological response, medical treatment approaches and adverse side-effects of drugs (22, 23). The aim of the present review is to discuss the emerging field of oncomiRs and tumor suppressor miRNAs and current insights of the involvement of these miRNAs in the pathogenesis of TGCTs. Furthermore, we describe and highlight their potential as novel diagnostic and prognostic biomarkers for future purposes in patients with TGCTs.


Aberrant expression of miRNAs correlates with various cancers, as well as with various types of TGCTs. Previous studies revealed that some miRNAs exhibit abnormal expressions in TGCTs samples as compare to normal testis. For example, down-regulation of miR-506~514 cluster was previously reported in seminomas and EC as compared to CIS and normal testis, suggesting its important role in TGCTs development (24). A former study has shown significantly lower miR-199a expression in TGCTs compared with normal testicular germ cells (25, 26). Likewise high miR-449 levels were found in normal testis, lung and trachea but were not detectable in testicular and other cancer cells (27). Furthermore, relatively higher expressions of miR-142-3p are found in TGCTs compared with normal testis (28). Other miRNAs such as miR-99a, miR-100 and miR-145 are reported to be down-regulated and; miR-512-3p, miR-515, miR-517~518 and miR-525 are up-regulated in TGCTs (29).

Some of the miRNAs are differentially expressed in histological subtypes of TGCTs. Such as miR-302 cluster is expressed both in EC and seminoma (30, 31) while its expression is down-regulated with differentiation of EC to teratomas but up-regulated in YST (32).The same expression pattern is found for miR-17-5p and miR-154 that is they are expressed in EC but down-regulated upon differentiation to teratomas (Figure 2) (31). Conversely another study found that miR-371~373 and miR-302 clusters are overexpressed in all malignant TGCTs regardless of histological subtypes and patient age (33) but they didn’t measured miR-302 cluster expressions in teratoma. Moreover, miR-301 is predominantly found in the more differentiated tissues, such as spermatocytic seminomas, YST and teratomas, whereas miR-301 is absent in EC (Figure 2) (31, 34). MiR-146 expression is lower in seminomas, spermatocytic seminomas, and even different types of non-seminomatous tumors such as EC and teratomas compared with normal testis (31).

Figure 2

(A) Schematic diagram showing aberrantly expressed miRNAs in TGCTs as compare to normal testes. miRNAs up-regulated (↑) or down-regulated (↓) in type III TGCTs are encircled by yellow, in non-seminoma are encircled by green and in seminoma are encircled by blue circle. (B) Expression pattern in different types and sub-types of TGCTs compare with each other. Red font shows miRNAs expression as compare to seminoma (red circle), blue font shows miRNAs expression as compare to embryonic carcinoma (EC) (blue circle) and black font shows other aberrantly expressed miRNAs in these types and subtypes of TGCTs.

3.1. miRNAs as tumor suppressors

Like a coding gene, a miRNA can act as a tumor suppressor with the loss of its function and can initiate or contribute to the malignant transformation of a normal cell. The loss of function of a miRNA could be due to several mechanisms, including genomic deletion, mutation, epigenetic silencing, and/or miRNA processing alterations (35, 3638). Advances in recent research suggest that some miRNAs can act as tumor suppressors via regulating tumor cell proliferation and invasion such as miR-133a, miR-133b and miR-145. Both miR-133b and miR-145 can target an oncogenic gene FSCNI concordantly and other target genes individually to control carcinogenesis (31, 39, 40). Anti-proliferation and anti-invasion effects of miR-199a were demonstrated and identified through its direct targets, PODXL and MAFB that mediates the tumor suppressor activity of miR-199a (Figure 3) (25, 26). Likewise, miR-449a and -b suppresses cell proliferation by activation of p53-induced mechanisms along with probable contribution by p53-independent mechanisms (27). MiR-125b is another tumor suppressor miRNA recently reported in TGCTs which suppresses tumor growth significantly via targeting tumor cell-derived chemokines CSF1 and CX3CL1, which are known to control the recruitment of tumor associated macrophages to tumor site (41).

Figure 3

MiRNA molecules implicated in the development of testicular cancer including their proposed functions and; predicted (normal font) and confirmed (bold font) targets. Blue color indicates tumor suppressor miRNAs, green color indicates oncomiRs while grey color indicates those miRNAs which are find to be aberrantly expressed in TGCTs, targets are predicted or confirmed but functions are not reported yet. * (57).

A possible connection between TGCTs and male infertility might be through a pathway which is regulated by miRNAs. Infertile men are nearly three-times more likely to develop TGCTs than are those who are fertile (42). Previous study reveals that miR-383 expression is down-regulated in the testis of infertile men with maturation arrest. And this down-regulation of miR-383 results in enhanced proliferation and reduced apoptosis of germ cells via targeting one of the tumor suppressor genes, IRF1 (43). Other miRNAs with a clear tumor suppressor role have also been reported, although the evidence supporting this claim is merely correlative. Substantial experimental data are lacking, and miRNA knockout mice that develop or are predisposed to TGCTs have not yet been reported.

3.2. miRNAs as oncomiRs

The list of miRNAs that function as oncomiRs is short, but the evidence for their role in TGCTs is very strong. Genome-wide miRNA profiling studies have provided evidence of miRNA up-regulations in TGCTs. It has been reported recently that oncogenic miRNAs suppress tumor suppressor genes and promote tumorigenesis (44). PTPN23 is one of the important tumor suppressor candidates and is involved in the tumorigenesis of various organs. In the absence of PTPN23 protein expression in human TGCTs relatively higher miR142-3p expression are observed, suggesting that miR142-3p plays an important role in the pathogenesis of TGCTs by repressing PTPN23 expression (28). Similarly miR-372 and miR-373 have been shown to play oncogenic roles in human TGCTs by targeting the tumor suppressor LATS2 (45). These two miRNAs promote cell proliferation and tumor development by neutralizing p53-mediated CDK inhibition, possibly through direct inhibition of expression of the tumor suppressor gene LATS2 (21, 45). To date, very few miRNAs have been functionally characterized in TGCTs. However, the functional roles of other differentially expressed miRNAs in TGCTs have yet to be characterized.

To study the remarkable responsiveness of TGCTs to miRNA dependent therapeutics, genetically engineered mouse models of TGCTs can be designed in future by conditionally activating oncomiRs and inactivating tumor suppressor miRNAs. Previously TGCTs mouse model has shown rapid germ cell tumorigenesis by activating oncogene Kras and inactivating tumor suppressor gene Pten. TGCTs in these mice were characterized histologically as teratoma grew bilaterally in some and unilaterally in other mice (46). Identification of the molecular features that make TGCTs responsive to miRNA therapeutics may yield broadly applicable biomarkers for chemosensitivity or chemoresistance and provide avenues for the development of more effective therapies for other cancers as well.


After tumor tissue-specific miRNAs were identified in the serum of patients, the idea was born that miRNAs could qualify as circulating biomarkers, a concept that is well-known for other molecular components such as circulating tumor cells or circulating free DNA (4751). In a research by Dieckmann et al. serum levels of miRNA-371~373 from 24 patients with TGCTs (20 seminoma and 4 non-seminomatous tumors) were quantified by reverse transcriptase polymerase chain reaction (52). Out of the three miRNAs quantified, miR-371a-3p showed impressive result as considerably high expression was revealed in untreated patients, with a strong decline after surgical removal of the tumor. In this study, 20 patients presented with clinical stage I disease. Only 25% showed elevation of the classical markers (alpha-fetoprotein, human chorionic gonadotropin), whereas 85% of patients had a higher level of miRNA-371a-3p when compared with the mean value of healthy controls. Moreover, in stage I disease, the serum level of miRNA 371a-3p decreased significantly after orchiectomy. In four patients with advanced disease serum levels of miRNA-371a-3p dropped into normal range of the control population after completion of chemotherapy treatment. Interestingly, neither a correlation between miRNA expression level in tumor tissue and serum, nor with the extent of tumor volume was observed (53). Another study, compared serum levels of miR-371~373, miR-302 and miR-367 from 80 patients with TGCTs with those of 47 healthy controls. MiR-371~373 and miR-367 showed the most promising results. By combining these miRNAs, a clear separation of tumor from control samples was made possible. The miRNAs had an overall sensitivity of 98%, whereas the traditional serum markers alpha-fetoprotein/human chorionic gonadotropin revealed only a sensitivity of 36% to 57%, which was even lower when applied for seminomas alone (30). These results underline the superiority of miRNAs for diagnosis and monitoring of stem cell components when compared to traditional markers. Further studies with larger patient cohorts are suggested to confirm these promising results.

miRNAs may increase sensitivity of TGCTs to clinically established chemotherapeutic drugs. TGCTs often represent curative disease, including advanced disease stages, when treated with chemotherapy. Nevertheless, short- and long-term side-effects such as infertility, renal impairment, lung toxicity and others can occur from chemotherapy. Moreover, expression levels of miRNA-302a have been associated with increased sensitivity of TGCTs to cisplatin. Up-regulation of miRNA-302 enhances cisplatin-induced G2/M phase arrest and subsequent apoptosis (53). On the other hand, cisplatin resistance has been associated with high levels of cytoplasmic p21. MiR-106b seed family members regulate p21 expression levels. OCT4 regulates the expression level of miR-106b. OCT3 and 4 are markers of pluripotency and are therefore expressed in embryonic stem cells and TGCTs but not in mature teratomas (54, 55). Improved prognostic tools are needed to categorize the risk of the individual patient in order to minimize such effects of treatment. miRNAs seem to have great potential as diagnostic, prognostic and, ultimately, therapeutic biomolecules for future perspective.


The rapidly progressing field of miRNAs continues to reveal the diversity and complexity of the RNA world. However, despite remarkable recent progress, the connection between TGCTs and miRNAs remains unclear with vague explanations to numerous unanswered questions. More sophisticated in vivo models are needed to identify and define miRNA functions because miRNAs can have significant effects on the transcriptome, while their full biological properties are unlikely to be explained by the suppression of a single or few proteins.

Although miRNAs only moderately suppresses their targets, miRNAs could exert both strong and broad effects, largely because they suppress many genes as they impact multiple feedback loops with other regulators of gene expression. Since modulating the level of a single miRNA could eventually affect many pathways at the same time, therefore, targets should be experimentally validated rather than predicted. Another potential challenge for future studies relates to the probabilistic tissue-specific functions of some miRNAs. The function of a given miRNA is dictated by numerous targets that are expressed in a given cell type.


In this review, we discussed miRNA regulation of target gene expression in relation to the establishment of TGCTs and discussed how miRNAs can act as oncomiRs and tumor suppressors. The characterization of the roles of the regulatory miRNAs in TGCTs and its prognosis requires further investigation and consolidation in both animal models and humans.


This work was supported by the Young Elite Scientists Sponsorship Program by CAST (grant no. YESS20160118 to Su-Ren Chen); National Natural Science Foundation of China (grant no. 31471352 to Yi-Xun Liu; 31501198 to Su-Ren Chen); CAS-TWAS President’s Fellowship for International PhD Students (to Aalia Batool); Clinical Capability Construction Project for Liaoning Provincial Hospitals (grant no. LNCCC-C09-2015, LNCCC-D50-2015) to Yi-Xun Liu and Academician Workstation Support (Shenyang, Changsha and Shandong) to Yi-Xun Liu.

AL Frazier C Weldon J Amatruda Fetal and neonatal germ cell tumors Semin Fetal Neonatal Med 2012 17 4 222 30 DOI:10.1016/j.siny.2012.05.004 PMid:22647545
A Bahrami JY Ro AG Ayala An overview of testicular germ cell tumors Arch Pathol Lab Med 2007 131 8 1267 80
DM Kristensen SB Sonne AM Ottesen RM Perrett JE Nielsen K Almstrup NE Skakkebaek H Leffers E Rajpert-De Meyts Origin of pluripotent germ cell tumours: the role of microenvironment during embryonic development Mol Cell Endocrinol 2008 288 1-2 111 8
P Baade P Carriere L Fritschi Trends in testicular germ cell cancer incidence in Australia Cancer Causes Control 2008 19 10 1043 9 DOI:10.1007/s10552-008-9168-z PMid:18478339
NE Skakkebaek E Rajpert-De Meyts N Jorgensen KM Main H Leffers AM Andersson A Juul TK Jensen J Toppari Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations Int J Androl 2007 30 4 198 204 discussion 204-5
M Walschaerts E Huyghe A Muller JM Bachaud L Bujan P Thonneau Doubling of testicular cancer incidence rate over the last 20 years in southern France Cancer Causes Control 2008 19 2 155 61 DOI:10.1007/s10552-007-9081-x PMid:18236173
L Richiardi A Pettersson O Akre Genetic and environmental risk factors for testicular cancer Int J Androl 2007 30 4 230 40 discussion 240-1
EL Aschim TB Haugen S Tretli T Grotmol Subfertility among parents of men diagnosed with testicular cancer Int J Androl 2008 31 6 588 94 DOI:10.1111/j.1365-2605.2007.00813.x PMid:17822418
DA Paduch Testicular cancer and male infertility Curr Opin Urol 2006 16 6 419 27 DOI:10.1097/01.mou.0000250282.37366.d2 PMid:17053522
SB Sonne K Almstrup M Dalgaard AS Juncker D Edsgard L Ruban NJ Harrison C Schwager A Abdollahi PE Huber S Brunak LM Gjerdrum HD Moore PW Andrews NE Skakkebaek E Rajpert-De Meyts H Leffers Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte Cancer Res 2009 69 12 5241 50 DOI:10.1158/0008-5472.CAN-08-4554 PMid:19491264 PMCid: PMC2869030
MR Lichinitser LS Bassalyk DM Levina LP Pashintseva AA Molodyk Study of various markers (alpha fetoprotein, chorionic gonadotropin, lactate dehydrogenase) during chemotherapy of malignant testicular tumors Ter Arkh 1984 56 6 77 9
GJ Bosl NL Geller C Cirrincione J Nisselbaum D Vugrin WF Whitmore Jr RB Golbey Serum tumor markers in patients with metastatic germ cell tumors of the testis. A 10-year experience Am J Med 1983 75 1 29 35 DOI:10.1016/0002-9343(83)91164-6
CG Ruf N Khalili-Harbi S Sachs H Isbarn W Wagner C Matthies V Meineke M Fisch FK Chun M Abend The search for biomarkers of metastatic seminoma J Urol 2013 190 3 1046 51 DOI:10.1016/j.juro.2013.04.022 PMid:23583226
V Ambros microRNAs: tiny regulators with great potential Cell 2001 107 7 823 6 DOI:10.1016/S0092-8674(01)00616-X
DP BarTel microRNAs: genomics, biogenesis, mechanism, and function Cell 2004 116 2 281 97 DOI:10.1016/S0092-8674(04)00045-5
JC Carrington V Ambros Role of microRNAs in plant and animal development Science 2003 301 5631 336 8 DOI:10.1126/science.1085242 PMid:12869753
BP Lewis CB Burge DP BarTel Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets Cell 2005 120 1 15 20 DOI:10.1016/j.cell.2004.12.035 PMid:15652477
Y Huang XJ Shen Q Zou SP Wang SM Tang GZ Zhang Biological functions of microRNAs: a review J Physiol Biochem 2011 67 1 129 39 DOI:10.1007/s13105-010-0050-6 PMid:20981514
G Di Leva CM Croce Roles of small RNAs in tumor formation Trends Mol Med 2010 16 6 257 67 DOI:10.1016/j.molmed.2010.04.001 PMid:20493775 PMCid: PMC2885513
A Bezan A Gerger M Pichler microRNAs in testicular cancer: implications for pathogenesis, diagnosis, prognosis and therapy Anticancer Res 2014 34 6 2709 13
SC McIver SD Roman B Nixon EA McLaughlin miRNA and mammalian male germ cells Hum Reprod Update 2012 18 1 44 59 DOI:10.1093/humupd/dmr041 PMid:21989172
H Ling M Fabbri GA Calin microRNAs and other non-coding RNAs as targets for anticancer drug development Nat Rev Drug Discov 2013 12 11 847 65 DOI:10.1038/nrd4140 PMid:24172333 PMCid: PMC4548803
D Bach J Fuereder M Karbiener M Scheideler AL Ress D Neureiter R Kemmerling O Dietze M Wiederstein F Berr K Plaetzer T Kiesslich M Pichler Comprehensive analysis of alterations in the miRNome in response to photodynamic treatment J Photochem Photobiol B 2013 120 74 81 DOI:10.1016/j.jphotobiol.2013.01.012 PMid:23466801
GW Novotny KC Belling JB Bramsen JE Nielsen J Bork-Jensen K Almstrup SB Sonne J Kjems E Rajpert-De Meyts H Leffers microRNA expression profiling of carcinoma in situ cells of the testis Endocr Relat Cancer 2012 19 3 365 79 DOI:10.1530/ERC-11-0271 PMid:22420006
HH Cheung AJ Davis TL Lee AL Pang S Nagrani OM Rennert WY Chan Methylation of an intronic region regulates miR-199a in testicular tumor malignancy Oncogene 2011 30 31 3404 15 DOI:10.1038/onc.2011.60 PMid:21383689 PMCid: PMC3117973
S Gu HH Cheung TL Lee G Lu WS Poon WY Chan Molecular mechanisms of regulation and action of microRNA-199a in testicular germ cell tumor and glioblastomas PLoS One 2013 8 12 e83980 DOI:10.1371/journal.pone.0083980 PMid:24391856 PMCid: PMC3877122
M Lize S Pilarski M Dobbelstein E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis Cell Death Differ 2010 17 3 452 8 DOI:10.1038/cdd.2009.188 PMid:19960022
K Tanaka K Kondo K Kitajima M Muraoka A Nozawa T Hara Tumor-suppressive function of protein-tyrosine phosphatase non-receptor type 23 in testicular germ cell tumors is lost upon overexpression of miR142-3p microRNA J Biol Chem 2013 288 33 23990 9 DOI:10.1074/jbc.M113.478891 PMid:23843459 PMCid: PMC3745344
M Port S Glaesener C Ruf A Riecke C Bokemeyer V Meineke F Honecker M Abend Micro-RNA expression in cisplatin resistant germ cell tumor cell lines Mol Cancer 2011 10 52
AJ Gillis MA Rijlaarsdam R Eini LC Dorssers K Biermann MJ Murray JC Nicholson N Coleman KP Dieckmann G Belge J Bullerdiek T Xu N Bernard LH Looijenga Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle Mol Oncol 2013 7 6 1083 92 DOI:10.1016/j.molonc.2013.08.002 PMid:24012110 PMCid: PMC5528443
AJ Gillis HJ Stoop R Hersmus JW Oosterhuis Y Sun C Chen S Guenther J Sherlock I Veltman J Baeten PJ van der Spek P de Alarcon LH Looijenga High-throughput microRNAome analysis in human germ cell tumours J Pathol 2007 213 3 319 28 DOI:10.1002/path.2230 PMid:17893849
MJ Murray HK Saini S van Dongen RD Palmer B Muralidhar MR Pett M Piipari CM Thornton JC Nicholson AJ Enright N Coleman The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression Mol Cancer 2010 9 290
RD Palmer MJ Murray HK Saini S van Dongen C Abreu-Goodger B Muralidhar MR Pett CM Thornton JC Nicholson AJ Enright N Coleman Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets Cancer Res 2010 70 7 2911 23 DOI:10.1158/0008-5472.CAN-09-3301 PMid:20332240 PMCid: PMC3000593
MR Suh Y Lee JY Kim SK Kim SH Moon JY Lee KY Cha HM Chung HS Yoon SY Moon VN Kim KS Kim Human embryonic stem cells express a unique set of microRNAs Dev Biol 2004 270 2 488 98 DOI:10.1016/j.ydbio.2004.02.019 PMid:15183728
GA Calin CD Dumitru M Shimizu R Bichi S Zupo E Noch H Aldler S Rattan M Keating K Rai L Rassenti T Kipps M Negrini F Bullrich CM Croce Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia Proc Natl Acad Sci U S A 2002 99 24 15524 9 DOI:10.1073/pnas.242606799 PMid:12434020 PMCid: PMC137750
GA Calin M Ferracin A Cimmino G Di Leva M Shimizu SE Wojcik MV Iorio R Visone NI Sever M Fabbri R Iuliano T Palumbo F Pichiorri C Roldo R Garzon C Sevignani L Rassenti H Alder S Volinia CG Liu TJ Kipps M Negrini CM Croce A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia N Engl J Med 2005 353 17 1793 801 DOI:10.1056/NEJMoa050995 PMid:16251535
Y Saito G Liang G Egger JM Friedman JC Chuang GA Coetzee PA Jones Specific activation of microRNA-127 with down-regulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells Cancer Cell 2006 9 6 435 43 DOI:10.1016/j.ccr.2006.04.020 PMid:16766263
T Nakamura E Canaani CM Croce Oncogenic All1 fusion proteins target Drosha-mediated microRNA processing Proc Natl Acad Sci U S A 2007 104 26 10980 5 DOI:10.1073/pnas.0704559104 PMid:17581865 PMCid: PMC1904159
M Kano N Seki N Kikkawa L Fujimura I Hoshino Y Akutsu T Chiyomaru H Enokida M Nakagawa H Matsubara miR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma Int J Cancer 2010 127 12 2804 14 DOI:10.1002/ijc.25284 PMid:21351259
T Qiu X Zhou J Wang Y Du J Xu Z Huang W Zhu Y Shu P Liu MiR-145, miR-133a and miR-133b inhibit proliferation, migration, invasion and cell cycle progression via targeting transcription factor Sp1 in gastric cancer FEBS Lett 2014 588 7 1168 77 DOI:10.1016/j.febslet.2014.02.054 PMid:24613927
A Batool YQ Wang XX Hao SR Chen YX Liu A miR-125b/CSF1-CX3CL1/tumor-associated macrophage recruitment axis controls testicular germ cell tumor growth Cell Death Dis 2018 9 10 962 DOI:10.1038/s41419-018-1021-z PMid:30237497 PMCid: PMC6148032
TJ Walsh MS Croughan M Schembri JM Chan PJ Turek Increased risk of testicular germ cell cancer among infertile men Arch Intern Med 2009 169 4 351 6 DOI:10.1001/archinternmed.2008.562 PMid:19237718 PMCid: PMC2881689
J Lian H Tian L Liu XS Zhang WQ Li YM Deng GD Yao MM Yin F Sun Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1 Cell Death Dis 2010 1 e94
KJ Mavrakis J Van Der Meulen AL Wolfe X Liu E Mets T Taghon AA Khan M Setty P Rondou P Vandenberghe E Delabesse Y Benoit NB Socci CS Leslie P Van Vlierbergh F Speleman HG Wendel A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL) Nat Genet 2006 43 7 673 8 DOI:10.1038/ng.858 PMid:21642990 PMCid: PMC4121855
PM Voorhoeve C le Sage M Schrier AJ Gillis H Stoop R Nagel YP Liu J van Duijse J Drost A Griekspoor E Zlotorynski N Yabuta G De Vita H Nojima LH Looijenga R Agami A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors Cell 2006 124 6 1169 81 DOI:10.1016/j.cell.2006.02.037 PMid:16564011
TM Pierpont AM Lyndaker CM Anderson Q Jin ES Moore JL Roden A Braxton L Bagepalli N Kataria HZ Hu J Garness MS Cook B Capel DH Schlafer T Southhard RS Weiss Chemotherapy-Induced depletion of OCT4-positive cancer stem cells in a mouse model of malignant testicular cancer Cell Repro 2017 21 7 1896 1909 DOI:10.1016/j.celrep.2017.10.078 PMid:29141221 PMCid: PMC5695237
E Heitzer P Ulz J Belic S Gutschi F Quehenberger K Fischereder T Benezeder M Auer C Pischler S Mannweiler M Pichler F Eisner M Haeusler S Riethdorf K Pantel H Samonigg G Hoefler H Augustin JB Geigl MR Speicher Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing Genome Med 2013 5 4 30 DOI:10.1186/gm434 PMid:23561577 PMCid: PMC3707016
PS Mitchell RK Parkin EM Kroh BR Fritz SK Wyman EL Pogosova-Agadjanyan A Peterson J Noteboom KC O'Briant A Allen DW Lin N Urban CW Drescher BS Knudsen DL Stirewalt R Gentleman RL Vessella PS Nelson DB Martin M Tewari Circulating microRNAs as stable blood-based markers for cancer detection Proc Natl Acad Sci U S A 2008 105 30 10513 8 DOI:10.1073/pnas.0804549105 PMid:18663219 PMCid: PMC2492472
MJ Murray N Coleman Testicular cancer: a new generation of biomarkers for malignant germ cell tumours Nat Rev Urol 2012 9 6 298 300 DOI:10.1038/nrurol.2012.86 PMid:22549310
J Wittmann HM Jack Serum microRNAs as powerful cancer biomarkers Biochim Biophys Acta 2010 1806 2 200 7 DOI:10.1016/j.bbcan.2010.07.002
E Heitzer M Auer EM Hoffmann M Pichler C Gasch P Ulz S Lax J Waldispuehl-Geigl O Mauermann S Mohan G Pristauz C Lackner G Hofler F Eisner E Petru H Sill H Samonigg K Pantel S Riethdorf T Bauernhofer JB Geigl MR Speicher Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer Int J Cancer 2013 133 2 346 56 DOI:10.1002/ijc.28030 PMid:23319339 PMCid: PMC3708119
KP Dieckmann M Spiekermann T Balks I Flor T Loning J Bullerdiek G Belge microRNAs miR-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours Br J Cancer 2012 107 10 1754 60 DOI:10.1038/bjc.2012.469 PMid:23059743 PMCid: PMC3493876
L Liu J Lian H Zhang H Tian M Liang M Yin F Sun microRNA-302a sensitizes testicular embryonal carcinoma cells to cisplatin-induced cell death J Cell Physiol 2013 228 12 2294 304 DOI:10.1002/jcp.24394 PMid:23625774
R Koster A di Pietro H Timmer-Bosscha JH Gibcus A van den Berg AJ Suurmeijer R Bischoff JA Gietema S de Jong Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer J Clin Invest 2010 120 10 3594 605 DOI:10.1172/JCI41939 PMid:20811155 PMCid: PMC2947220
LH Looijenga AJ Gillis H Stoop R Hersmus JW Oosterhuis Relevance of microRNAs in normal and malignant development, including human testicular germ cell tumours Int J Androl 2007 30 4 304 14 discussion 314-5
A Mclntyre D Gilbert N Goddard L Looijenga J Shipley Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adults Genes Chromosomes Cancer 2008 47 7 547 57 DOI:10.1002/gcc.20562 PMid:18381640
SL Lin DC Chang SY Ying D Leu DT Wu microRNA miR-302 inhibits the tumorigenecity of human pluripotent stem cells by coordinate suppression of the CDK2 and CDK4/6 cell cycle pathways Cancer Res 2010 70 22 9473 82 DOI:10.1158/0008-5472.CAN-10-2746 PMid:21062975
Back to top