Exosomal microRNA‐15a from ACHN cells aggravates clear cell renal cell carcinoma via the BTG2/PI3K/AKT axis

Abstract

Abstract Accumulating studies have indicated that exosomal microRNAs (miRNAs/miRs) can mediate clear cell renal cell carcinoma (ccRCC) at the early stage, but the mechanisms remain to be specified. Here, we investigated the mechanism of exosomal miR‐15a in ccRCC. After successful isolation of exosomes from RCC cells, we found that miR‐15a was upregulated in ccRCC cells. Moreover, upregulation of miR‐15a by pre‐miR‐15a promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition of ccRCC cells. A luciferase assay revealed that B‐cell translocation gene 2 (BTG2) was a target gene of miR‐15a and negatively correlated with miR‐15a expression. BTG2 was poorly expressed in ccRCC, which reduced the proliferation of ccRCC cells. In addition, overexpression of BTG2 could reverse the promotive effects of miR‐15a on ccRCC. Furthermore, BTG2 reduced PI3K/AKT pathway activity. Our results collectively indicated that exosomal miR‐15a from RCC cells accelerated cell viability by downregulating BTG2 and promoting the activity of the PI3K/AKT signaling pathway. We demonstrated a novel mechanism by which exosomal miR‐15a exerted pro‐proliferatory effects on ccRCC, highlighting the potential of exosomal miR‐15a as a target for ccRCC prognosis.

Keywords

• B‐cell translocation gene 2
• clear cell renal cell carcinoma
• exosomes
• microRNA‐15a
• PI3K/AKT pathway