Urinary exosome miR-30c-5p as a biomarker of clear cell renal cell carcinoma that inhibits progression by targeting HSPA5.

Exosome-derived miRNAs are regarded as biomarkers for the diagnosis and prognosis of many human cancers. However, its function in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, differentially expressed miRNAs from urinal exosomes were identified using next-generation sequencing (NGS) and verified using urine samples of ccRCC patients and healthy donors. Then, the exosomes were analysed in early-stage ccRCC patients, healthy individuals and patients suffering from other urinary system cancers. Thereafter, the target gene of the miRNA was detected. Its biological function was investigated in vitro and in vivo. The results showed that miR-30c-5p could be amplified in a stable manner. Its expression pattern was significantly different only between ccRCC patients and healthy control individuals, but not compared with that of other urinary system cancers, which indicated its specificity for ccRCC. Additionally, the overexpression of miR-30c-5p inhibited ccRCC progression in vitro and in vivo. Heat-shock protein 5 (HSPA5) was found to be a direct target gene of miR-30c-5p. The depletion of HSPA5 caused by miR-30c-5p inhibition reversed the promoting effect of ccRCC growth. In conclusion, urinary exosomal miR-30c-5p acts as a potential diagnostic biomarker of early-stage ccRCC and may be able to modulate the expression of HSPA5, which is correlated with the progression of ccRCC.