Micro-RNA378a-3p Induces Apoptosis in Sarcomatoid Renal Cell Carcinoma and Regulates POLR2A and RUNX2 Expression

Abstract

Background/Aim: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive subtype of RCC. In the current study, we investigated whether the POLR2A and RUNX2 genes are involved in RCC-related signaling pathway and associated with miR-378. Materials and Methods: Thirteen formalin-fixed and paraffin-embedded RCC samples were collected. Three software programs were used to predict the potential gene regulation in RCC by miR-378 and immunohistochemistry analysis was applied to confirm the expression of targeted proteins in FFPE samples. MicroRNA-378 transfection, analysis of mRNA and protein expression via Western Blotting and cell apoptosis analysis via flow cytometry for POLR2A and RUNX2 were further studied in four renal cell carcinoma cell lines. Results: Both the mRNA and protein expression levels of POLR2A and RUNX2 in sRCC cell lines and were significantly higher than those in other subtypes of RCC, and similar results were obtained in clinical samples (p<0.01). Second, overexpression of miR-378 significantly suppressed the expression of POLR2A and RUNX2 in sRCC cells (p<0.01) and enhanced apoptosis (p<0.05). Conclusion: miR-378 significantly inhibits the expression of POLR2A and RUNX2 in sRCC and further promotes apoptosis of sRCC cells. We speculated that the apoptosis mechanism in sRCC occurs via regulation of the ERK2 and PI3K/AKT pathways, which might distinguish it from other subtypes of RCC.