Objective: The aim of the current study was to elucidate the role of miR-455-3p in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and its prognostic value in patients with ESCC.
Patients and methods: Expression levels of miR-455-3p and FAM83F mRNA in ESCC tissues and adjacent normal tissues were detected by quantitative RT-PCR. The X2-test was used to assess miR-455-3p expression on clinicopathological parameters. The association with overall survival of patients was analyzed by Kaplan-Meier survival analysis. Cox's multivariate regression model was performed to identify independent prognostic factors of overall survival. The effect of miR-455-3p on proliferation was evaluated by kit-8 (CCK-8), and cell invasion was evaluated by transwell assays. The molecular target of miR-455-3p was identified using a computer algorithm and confirmed experimentally. Furthermore, the effect of miR-455-3p up-regulation on FAM83F expression was examined by Western blot.
Results: miRNA-455-3p was significantly increased in ESCC tissues and cell lines. Also, miR-455-3p expression was significantly associated with histological grade, lymph nodes metastasis and clinical stage (all p < 0.05). The patients with low miR-455-3p expression had shorter survival time than those with high miR-455-3p expression. Furthermore, univariate and multivariate analysis identified low miR-455-3p expression as an unfavorable prognostic factor for overall survival. Moreover, transfection with the miR-455-3p mimic enhanced the cell proliferation and invasion in ESCC cells. Luciferase reporter assays confirmed that miR-455-3p binding to the 3'-UTR regions of FAM83F inhibited the expression of FAM83F in ESCC cells. Western blot confirmed that overexpression of miR-455-3p resulted in down-regulation of FAM83F in ESCC cells.
Conclusions: Our findings indicate that miR-455-3p plays an anti-oncogenic role in the development of ESCC by downregulation of FAM83F and could be an independent marker for predicting the clinical outcome of ESCC patients.