జర్నల్ ఆఫ్ ఇంటిగ్రేటివ్ ఆంకాలజీ

Down-Regulated Mir-22 as Predictive Biomarkers for Prognosis of Cervical Cancer

Abstract

Tingting Zhang, Xiang Xue, Dalin He and Jer-Tsong Hsieh

Background: microRNA-22 (miR-22) was frequently altered in numerous cancers and was involved in various cellular processes related to carcinogenesis. However, the role of miR-22 in cervical cancer haven’t been investigated.
Methods: 62 pairs of fresh cervical cancer tissue were collected between May 2012 and March 2015. Real-time quantitative RT-PCR assay was performed to evaluate the expression levels of miR-22. The survival curves were determined using the Kaplan-Meier method and Cox regression for statistics. The roles of miR-22 in cell proliferation, migration and invasion were identified using miR-22 mimic-transfected cells. In addition, the regulatory effect of miR- 22 on suppressor of cancer cell invasion (SCAI) was evaluated using qRT-PCR a dual luciferase reporter assay.
Results: miR-22 expression in cervical cancer tissues was significantly lower than that in normal tissues (mean ± SD: 1.944 ± 1.026 vs. 4.981 ± 1.507, P < 0.0001). Low miR-22 expression level was correlated with FIGO stage (P = 0.00004), tumor differentiation (P = 0.0002), and lymph-node-metastasis stage (P = 0.0099). Kaplan-Meier analysis with the log-rank test indicated that low miR-22 expression had a significant impact on overall survival (P = 0.0016) and progression-free survival (P = 0.0005). Moreover, ectopic miR-22 expression potently inhibited cervical cancer cell growth (P < 0.01), migration (P < 0.01) and invasion (P < 0.01) in vitro. miR-22 overexpression in cervical cancer cell lines decreased MMP1 and MAPK1 expression at the translational level and reduced MMP1/MAPK1- driven luciferase-reporter activity (P < 0.01).
Conclusions: Our data demonstrated that the expression of miR-22 was downregulated in cervical cancer, and associated with overall survival as well as progression-free survival, suggesting that miR-22 could serve as an efficient prognostic factor for cervical cancer patients.