Identification a ceRNA (XIST/miR-10a-5p/SERPINE1) Axis as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma.

Abstract

Background: Kidney cancer is one of the most common malignancies, of which the most aggressive subtype was kidney renal clear cell carcinoma (KIRC), accounting for 80% of them. A growing number of studies point to the involvement of competitive endogenous RNAs in tumor development. However, the role of ceRNA network involved in KIRC remains unclear. Thus, the aim of this study was to investigate the BAP1-associated prognostic ceRNA in KIRC. Methods: We downloaded the RNAseq data from TCGA along with the relevant clinical data. We screened the differentially expressed lncRNAs, miRNAs, mRNAs according to the expression of BAP1 and established a ceRNA network. Results: After comprehensive bioinformatics analysis, we identified the XIST-miR-10a-5p-SERPINE1 ceRNA axis. Next, we confirmed the prognostic role of miR-10a-5p/SERPINE1 in KIRC using survival analysis and Cox regression analysis. To investigate the abnormally high expression of SERPINE1, we performed methylation analysis of SERPINE1 and concluded that the methylation level of SERPINE1 in KIRC was significantly lower than that in normal tissues. Furthermore, to study the role of SERPINE1 in the immune microenvironment in KIRC, we performed immune cell infiltration analysis and found that SERPINE1 expression was positively correlated with the level of multiple immune cell infiltration (CD 4+ T cell, CD 8+ T cell, macrophages, dendritic cells, neutrophils). Conclusion: We constructed a ceRNA (XIST/has-miR-10a-5p/SERPINE1) that can be used as prognostic biomarker of KIRC. Furthermore, we found that miR-10a-5p/SERPINE1 were significantly associated with clinical features and were independent prognostic factors of KIRC.

Advances in targeting of miR‑10‑associated lncRNAs/circRNAs for the management of cancer (Review)

“…In addition, it has been shown that lncRNAs are involved in the immune process of the tumor microenvironment (TME) ( 80 ). For example, Liu et al ( 81 ) showed that a lncRNA XIST/miR-10a-5p/SERPINE1 axis mediated the TME of ccRCC. Immune cell infiltration analysis revealed that the lncRNA XIST can regulate the levels of CD4 + T cells, CD8 + T cells, macrophages, dendritic cells, neutrophils and other immune-related cells through the regulation of miR-10a-5p targeting SERPINE1 expression ( 81 ).…”

“…For example, Liu et al ( 81 ) showed that a lncRNA XIST/miR-10a-5p/SERPINE1 axis mediated the TME of ccRCC. Immune cell infiltration analysis revealed that the lncRNA XIST can regulate the levels of CD4 + T cells, CD8 + T cells, macrophages, dendritic cells, neutrophils and other immune-related cells through the regulation of miR-10a-5p targeting SERPINE1 expression ( 81 ). Another study showed that lncRNA NEAT1 similarly promoted the proliferation and migration of 786-O and ACHN kidney renal clear cell carcinoma (KIRC) cells by acting as a sponge of miR-10a-5p, thus indirectly activating SERPINE1.…”