MiR-638 inhibits cervical cancer metastasis through Wnt/β-catenin signaling pathway and correlates with prognosis of cervical cancer patients

摘要

OBJECTIVE: MiR?638 has been demonstrated to be correlated with several tumor progressions. However, the exact role of miRNA-638 in cervical cancer (CC) has not been investigated. The aim of present study was to explore the prognostic value of miR-638 in patients with CC and analyze molecular mechanisms of miR-638 in CC progression. PATIENTS AND METHODS: Real-time quantitative RT-PCR was performed to measure miR-638 expression level in 196 paired of CC and matched normal tissues, CC cell lines. The correlation of miR-638 with clinicopathological features and prognosis was analyzed. Furthermore, the effects of miR-638 on tumorigenicity of CC cells were evaluated by functional assays. Finally, Western blot was used to evaluate the activation of Wnt/β-catenin signaling pathway. RESULTS: We found that miR-638 expression was downregulated in CC tissues and cell lines compared with the adjacent normal tissues and normal cell lines. In addition, low expressions of miR-638 were significantly associated with advanced FIGO stage (p =0.007), lymph node metastasis (p = 0.018) and vascular invasion (p = 0.002). Moreover, the results of Kaplan-Meier method showed that CC patients with lower miR-638 expression had significantly poorer overall survival (p = 0.0023) and progression-free survival (p = 0.0005). In a multivariate Cox model, we found that miR-638 expression was an independent prognostic factor for both overall survival and progression-free survival in patients with CC (both p = 0.001). In vitro assay showed that miR-638 overexpression suppressed cell migration and invasion of HeLa cells. The results of Western blot indicated that over-expression of miR-638 inhibited the activation of Wnt/β-catenin signaling pathway. CONCLUSIONS: Our findings firstly showed that miR-638 might serve as a tumor suppressor. In the future, miR-638 might be regarded as a therapeutic target and a potential prognostic factor in human CC.