MicroRNA-138 is a potential biomarker and tumor suppressor in human cervical carcinoma by reversely correlated with TCF3 gene

Abstract

BackgroundThe aim of our work is to identify the functional mechanism of microRNA-138 (miR-138) in human cervical cancer. MethodsMiR-138 expression was investigated by qRT-PCR in cervical cancer cell lines and human tumors. Correlations of patients' clinicopathological factors and overall survival with miR-138 expression were analyzed. In SiHa and HeLa cells, miR-138 was either upregulated or downregulated to evaluate its regulations on cervical cancer in vitro proliferation, invasion and in vivo xenograft growth. Downstream target gene of miR-138, TCF3, was analyzed by dual-luciferase reporter assay, and by qRT-PCR to evaluate its expression in cervical tumors and cervical cancer cell lines. TCF3 was either upregulated or downregulated in SiHa and HeLa cells to further evaluate its role in regulating cervical cancer proliferation and invasion. ResultsMiR-138 is downregulated in both cervical tumors and cervical cancer cell lines. Low expression of miR-138 in cervical tumors is closely correlated with patients' clinicopathological factors and poor survival. In SiHa and HeLa cells, lentivirus-induced miR-138 upregulation inhibited cancer proliferation and invasion in vitro, and xenograft growth in vivo, whereas miR-138 downregulation had little effect. TCF3 was confirmed to be regulated by miR-138, and upregulated in cervical cancer tumors and cell lines. In vitro cervical cancer proliferation and invasion were significantly inhibited by SiRNA-mediated TCF3 downregulation, but unaffected by TCF3 overexpression. ConclusionMiR-138 may be a tumor suppressor and potential prognostic biomarker in cervical cancer. Its downstream target, TCF3, may also regulate cancer development in a reverse manner as miR-138.