MicroRNA-23b suppresses cervical cancer biological progression by directly targeting six1 and affecting epithelial-to-mesenchymal transition and AKT/mTOR signaling pathway.

Abstract

To elucidate the effects and mechanism of microRNA-23b (miR-23b) in cervical cancer (CC) progression. Fifty-six pairs of CC tissue samples and matched para-carcinoma tissue samples were collected. Meanwhile, human normal cervical epithelial cell and CC cell lines were cultured. The abilities of cell proliferation and migration were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays and transwell assays. The correlation between sine oculis homeobox 1 (six1) and miR-23b was clarified by dual-luciferase reporter assay. The relative protein and mRNA expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and Western blot. In addition, Xenograft tumor formation assay was performed in this study. MiR-23b was remarkably down-regulated in CC and the low miR-23b expressions were associated with the poor prognosis and worse OS of CC patients. Additionally, the functional assays demonstrated that miR-23b overexpression obviously repressed CC cell proliferation, invasion and migration abilities through the regulation of the AKT/mTOR pathway and the epithelial-to-mesenchymal transition (EMT) progress. Moreover, the luciferase reporter assay indicated that six1 was one functional target for miR-23b in CC cells, indicating that the inhibitory functions of miR-23b in CC cells were partially regulated by six1. Moreover, miR-23b restoration could prominently repress tumor growth in vivo. MiR-23b suppressed CC progression via directly targeting six1 and affecting AKT/mTOR signaling pathway as well as EMT progress. Therefore, miR-23b/six1 may be promising biomarkers for CC diagnosis and therapy.