The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

Abstract

AbstractMicroRNAs (miRNAs) have been reported to be involved in the initiation and progression of human tumors including cervical cancer (CC). However, the mechanisms underlying of their actions in CC remain to be fully elucidated. Herein, the differentially expressed miRNAs that were screened based on GSE55940 microarray data retrieved from Gene Expression Omnibus (GEO), and miR-103a-3p was significantly upregulated in CC tissues which was selected as the target miRNA for further research. We also found that high expression of miR-103a-3p was closely associated with histological grades, FIGO stage and distant metastasis as well as reflected poor overall survival. Moreover, miR-103a-3p inhibition decreased the growth capacity of SiHa and HeLa cells by inducing cell apoptosis. And F-box and WD repeat-domain containing protein 7 (FBXW7), a well-known tumor suppressor in many cancer types, was identified as a direct target of miR-103a-3p. It was further found that FBXW7 was significantly downregulated in CC tissues, and it was inversely correlated with miR-103a-3p expression levels. Further investigation demonstrated that FBXW7 upregulation could simulate the roles of miR-103a-3p knockdown in cell viability and apoptosis. Moreover, FBXW7 knockdown efficiently abrogated the influences of CC cells proliferation caused by miR-103a-3p inhibition. Notably, miR-103a-3p could block FBXW7 mediated the downstream transcription factor pathways. Taken together, these findings suggest that miR-103a-3p functions as an oncogene in CC by targeting FBXW7.