Mitochondrial miRNA miR-134-5p Play Oncogenic Role in Clear Cell Renal Cell Carcinoma.

Abstract

Mitochondrial miRNAs (mitomiRs), which are miRNAs that located within mitochondria, have emerged as crucial regulators in a variety of human diseases, including multiple types of cancers. However, the specific role of mitomiRs in clear cell renal cell carcinoma (ccRCC) remains elusive. In this study, we employed a combination of experimental and bioinformatic approaches to uncover the diverse and abundant subcellular distribution of miRNAs within mitochondria in ccRCC. Notably, RNA sequencing after mitochondrial fractionation identified miR-134-5p as a miRNA predominantly detected in the mitochondria of 786O cells, and its expression is significantly upregulated compared to that in 293T cells. Differential expression and survival analyses from TCGA reveal that the upregulation of miR-134-5p is prevalent and closely associated with poor survival outcomes in ccRCC patients. Functionally, exogenous overexpression of miR-134-5p mimics promotes migration in both 786O and Caki-1 cells. Mechanistically, overexpressing the miR-134-5p mimic dramatically downregulates the mRNA levels of CHST6, SFXN2, and GRIK3, whereas the miR-134-5p inhibitor markedly upregulates their expression. Notably, these target mRNAs also predominantly detected in the mitochondria of 786O cells. The downregulated expression signatures of CHST6, SFXN2, and GRIK3 are also closely correlated with poor survival outcomes in ccRCC patients. Taken together, our work identifies a novel mitomiR, miR-134-5p, in ccRCC, provides potential targets that could serve as effective biomarkers for ccRCC diagnosis and prognosis, and opens new avenues for understanding the mitomiR-directed regulatory network in ccRCC progression.