MicroRNA-142-3p promotes renal cell carcinoma progression by targeting RhoBTB3 to regulate HIF-1 signaling and GGT/GSH pathways

Abstract

MicroRNAs play a critical regulatory role in different cancers, but their functions in renal cell carcinoma (RCC) have not been elucidated. Reportedly, miR-142-3p is involved in the tumorigenesis and the development of RCC in vitro and is clinically correlated with the poor prognosis of RCC patients. However, the molecular target of miR-142-3p and the underlying mechanism are unclear. In this study, we found that miR-142-3p was upregulated in RCC tumor tissues and downregulated in exosomes compared to normal tissues. The expression of miR-142-3p was inversely associated with the survival of patients with kidney renal clear cell carcinoma (KIRC). RhoBTB3 was reduced in RCC, and miR-142-3p plays an inverse function with RhoBTB3 in KIRC. The direct interaction between RhoBTB3 and miR-142-3p was demonstrated by a dual luciferase reporter assay. miR-142-3p promoted metastasis in the xenograft model, and the suppression of miR-142-3p upregulated RhoBTB3 protein expression and inhibited the mRNAs and proteins of HIF1A, VEGFA, and GGT1. Also, the miR-142-3p overexpression upregulated the mRNA of HIF1A, VEGFA, and GGT1. In conclusion, miR-142-3p functions as an oncogene in RCC, especially in KIRC, by targeting RhoBTB3 to regulate HIF-1 signaling and GGT/GSH pathways, which needs further exploration.