IMR Press / FBL / Volume 28 / Issue 12 / DOI: 10.31083/j.fbl2812354
Open Access Original Research
Effects of Purine Metabolism-Related LINC01671 on Tumor Heterogeneity in Kidney Renal Clear Cell Carcinoma
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1 Department of Nephrology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, 410005 Changsha, Hunan, China
2 Department of Nephrology, The First Affiliated Hospital of Hunan Normal University, 410005 Changsha, Hunan, China
3 Nephrology Department and Laboratory of Kidney Disease, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, 410005 Changsha, Hunan, China
4 Department of Nephrology, Changsha Clinical Research Center for Kidney Disease, 410002 Changsha, Hunan, China
5 Department of Nephrology, Hunan Clinical Research Center for Chronic Kidney Disease, 410002 Changsha, Hunan, China
*Correspondence: chenyusa117@126.com (Yu-Sa Chen)
Front. Biosci. (Landmark Ed) 2023, 28(12), 354; https://doi.org/10.31083/j.fbl2812354
Submitted: 24 July 2023 | Revised: 14 September 2023 | Accepted: 20 September 2023 | Published: 27 December 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Renal cell carcinoma has several subtypes, with kidney renal clear cell carcinoma (KIRC) being the most common and heterogeneous. Purine metabolism is associated with cancer progression. However, the role of purine metabolism-related long non-coding RNAs (lncRNAs) in KIRC remains unknown. Methods: KIRC were grouped into Cluster-1 and Cluster-2 based on purine genes. Limma package was used to identify differentially expressed lncRNAs between two classes of purine genes. Single-factor screening was used followed by random forest dimensionality reduction and Lasso method to screen lncRNAs. A risk score model (Purine Score) containing the 3 lncRNAs was developed using the Lasso method. Results: A total of 22 differentially expressed lncRNAs were identified. These were reduced to a final set of three (LINC01671, ARAP1-AS1 and LINC02747). Age and metastasis (M) were identified as independent prognostic factors for KIRC using univariate and multivariate Cox analysis. An abnormal immune cell response was also associated with patient survival. The Purine Score correlated with abnormal expression of immune checkpoint genes. Genetic analysis of KIRC found somatic mutations in TP53, TRIOBP, PBRM1, PKHD1, VHL, NPHP3, TLN2, CABIN1, ABCC6, XIRP2, and CHD4. In vitro cell experiments showed that knockdown of LINC01671 promoted the proliferation and migration of 786-O cells, while inhibiting apoptosis. Overexpression of LINC01671 inhibited the proliferation and migration of CAKI-1 cells, while promoting apoptosis. Gene Set Enrichment Analysis (GSEA) analysis revealed that LINC01671 was significantly enriched in the MAPK, NF-kappa B, mTOR, PI3K-Akt, and Wnt signaling pathways. Conclusions: LINC01671 may be a novel prognostic marker with important therapeutic value for KIRC.

Keywords
purine metabolism
LINC01671
tumor heterogeneity
kidney renal clear cell carcinoma
Funding
2019SK4009/Hunan Clinical Research Center for Chronic Kidney Disease
2021JJ40290/Natural Science Foundation of Hunan Province
22C0034/Hunan Provincial Department of Education
21B0038/Hunan Provincial Department of Education
BSJJ202006/Doctoral Fund and 2020 national self-cultivation project
2023JJ60454/Natural Science Foundation of Hunan Province
Figures
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