FOXO3a Negatively Regulates miR-155-5p Expression to impact the proliferation and invasion of Renal Cell Carcinoma

Abstract The development of targeted therapy and biotherapy drug resistance is the major barrier in terminal Renal Cell Carcinoma (RCC) therapy. Emerging evidence revealed that FOXO3a could be regulated to suppress RCC. In this study, the regulatory mechanism of FOXO3a on miR-155 and their specific effects in the development of RCC were investigated. We found that FOXO3a was down-regulated in RCC tissues and cell lines, whereas miR-155-5p was highly expressed. Furthermore, the expression of FOXO3a was negatively correlated to miR-155-5p, while FOXO3a was clinically correlated with TNM stages and lymphatic metastasis. The mechanism study showed that FOXO3a transcriptionally regulates miR-155-5p expression by binding to the miR-155 Host gene promoter to regulate the biosynthesis of pre-miR-155. In addition, FOXO3a suppressed the proliferation and migration of RCC cells by regulating miR-155-5p expression. In searching for the downstream targets of miR-155-5p, we found that miR-155-5p suppressed the expression of DUSP-14. Furthermore, FOXO3a up-regulated DUSP-14 expression by down-regulating miR-155-5p. The findings suggest that FOXO3a negatively regulates miR-155-5p expression to impact the proliferation and invasion of renal cell carcinoma.