LINC00461 affects the survival of patients with renal cell carcinoma by acting as a competing endogenous RNA for microRNA‑942.

Abstract

The present study aimed to investigate the potential mechanisms of human miR-942 in the sunitinib-resistance of renal cell carcinoma (RCC). A sunitinib-resistant OS-RC-2 cell line was established by continuous exposure to increasing concentrations of sunitinib for ~12 weeks. The expression levels of four miRNAs were determined by reverse transcription-quantitative (RT-q)PCR. miR-942 mimics were transfected into OS-RC-2 cells and RNA sequencing was performed on the miR-942- and negative control-transfected cells. Downregulated genes, including those of long non-coding RNAs (lncRNAs) and mRNAs, were identified. The target genes of miR-942 were predicted, followed by protein-protein interaction network construction and functional enrichment analyses of miR-942 target genes. In addition, RCC RNA-seq and miRNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) database. The contributions of lncRNA and/or mRNAs to survival prediction were assessed and a competing endogenous RNA (ceRNA) network consisting of miR-942, lncRNA and mRNAs was constructed. The expression levels of LINC00461, miR-942, spalt-like transcription factor 1 (SALL1), methionyl aminopeptidase 1 (METAP1) and DDB1 and CUL4 associated factor 1 (DCAF11) were verified using RT-qPCR. The role of LINC00461 in cell viability was detected by MTT assay. The expression level of miR-942 was significantly increased in sunitinib-resistant cells. A total of seven lncRNAs and 155 mRNAs were predicted as target genes of miR-942 in the miR-942 mimic-treated samples, compared with the mimic control-treated group. These potential target genes were significantly associated with ‘protein binding’, ‘TNF-β signaling pathway’, ‘negative transcriptional regulation’ and ‘RNA binding’. Through the integrated analysis of RNA-sequencing and TCGA data, an miR-942-related ceRNA network, which was predicted to significantly affect the survival of patients with RCC, was constructed. The expression levels of lncRNA LINC00461 and the genes SALL1, METAP1, and DCAF11 were further verified. The viability of OS-RC-2 cells was decreased following co-transfection with miR-942 mimics and LINC00641 siRNA, and was comparable to that of wild type OS-RC-2 cells (P>0.05). Therefore, lncRNA LINC00461 may act as an miR-942 ceRNA, and affect the survival of patients with RCC by regulating the expression of SALL1, METAP1 and DCAF11.