Differential Expression of hsa-miR-34c-5p, hsa-miR-200b-3p, hsa-miR-320a-3p and Their Target Genes Determine Survival in Clear-Cell Renal Cell Carcinoma.

Abstract

Renal cell carcinoma (RCC) is the most common type of kidney cancer and significant patient population experiences relapse and metastasis, resulting in poor survival outcomes. Therefore, there is a need to identify novel biomarkers and therapeutic targets to monitor RCC progression and improve patient outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression and have been implicated in tumor progression. We analysed publicly available datasets to identify differentially expressed miRNAs and their putative targets were identified using miRDB and Starbase ENCORI database. Further, We analysed the expression levels of identified miRNAs and their selected target mRNAs by qRT-PCR. Diagnostic potential of miRNAs were analysed by ROC analysis.  Cox regression analysis were performed with target mRNAs to evaluate the potential prognostic utility and their association with clinical outcomes in ccRCC patients. hsa-miR-200b-3p, hsa-miR-320a-3p were downregulated and hsa-miR-34c-5p was upregulated in ccRCC patients. The target genes of identified miRNAs are critical regulators of the OXPHOS, cell death, and inflammatory pathways, involved in the progression of ccRCC. hsa-miR-200b-3p has an AUC of 0.7273 (p < 0.05; cutoff 3.870, LR+ 4.77). Univariable and multivariable cox regression analysis showed low expression of NDUFS1 independently associated with poor survival outcome (p < 0.001) in ccRCC patients. Our study demonstrated, downregulation of hsa-miR-200b-3p in ccRCC holds promise as a potential diagnostic biomarker and its identified target NDUFS1 as an independent prognostic biomarker for patients with ccRCC. These findings need to be validated in a large cohort of patients with RCC.