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MicroRNA‐492 overexpression involves in cell proliferation, migration, and radiotherapy response of cervical squamous cell carcinomas

2017; Wiley; Volume: 57; Issue: 1 Linguagem: Inglês

10.1002/mc.22717

1098-2744

Mei Liu, Jusheng An, Manni Huang, Liming Wang, Binbin Tu, Yan Song, Kai Ma, Yu Wang, Shuren Wang, Hongxia Zhu, Ningzhi Xu, Lingying Wu,

Cancer-related molecular mechanisms research

MicroRNAs (miRNAs) are small non‐coding RNA that target protein‐coding mRNAs at the post‐transcriptional level. The aim of this study was to define the role of miR‐492 in cervical squamous cell carcinomas. After microRNA profiling and comparison, we firstly detected miR‐492 expression in 104 tumor tissues biopsies derived from advanced staged (FIGO IIB‐IIIB) cervical squamous cell carcinoma patients before receiving concomitant chemoradiotherapy and found miR‐492 expression was significantly higher in the specimens that were sensitive to concomitant chemoradiotherapy, as compared with insensitive cancer specimens ( P < 0.05). Moreover, higher expression of miR‐492 was associated with pelvic lymph node metastasis (LNM) ( P < 0.05). Further studies illustrated ectopic miR‐492 overexpression in SiHa cells promoted cell proliferation, migration, and enhanced the sensitivity of cervical cancer cells to irradiation by promoting apoptosis. In addition, we identified TIMP2 as a direct miR‐492 target, which has been shown to be critical in modulating cancer cell migration and invasion. We also confirmed that miR‐492 expression levels in positive pelvic LNM were much higher than negative LNM and miR‐492 played a vital role in pelvic lymph node metastasis via regulating miR‐492/TIMP2/MMP10 axis. In particular, miR‐492 was correlated with prognosis in the subgroup of patients with negative pelvic LNM ( P < 0.05) and had a promising value in predicting treatment response in the subgroup of patients with positive pelvic LNM (an AUC of 85%, 75.00% specificity, and 95.24% sensitivity). Taken together, the results suggested that miR‐492 may serve as a potential biomarker for cervical cancer treatment and prognosis.