Down-regulation of miRNA-320c promotes tumor growth and metastasis and predicts poor prognosis in human glioma

作者:Lv, Qiao-Li; Zhu, Hui-Ting; Li, Hong-Mi; Cheng, Xiao-Hua; Zhou, Hong-Hao*; Chen, Shu-Hui*
来源:Brain Research Bulletin, 2018, 139: 125-132.
DOI:10.1016/j.brainresbull.2018.02.009

摘要

Emerging studies show that dysregulated miRNAs are implicated in tumorigenesis and progression of various cancers. MiRNA-320c, an important member of miRNA-320 family, was characterized as a new candidate miRNA that suppressed the development of colorectal cancer and bladder cancer. However, the function of miRNA-320c in human glioma remained unclear. Here, we found that miRNA-320c was significantly down regulated in glioma tissues in contrast with normal brain tissues, being tightly related to clinical stage of glioma by qRT-PCR. Moreover, Kaplan-Meier analysis demonstrated that patients with low miRNA-320c expression had a shorter survival. Multivariate Cox regression analysis indicated that miRNA-320c could serve as an independent poor prognostic factor for patients with glioma. Functionally, overexpression of miRNA-320c could dramatically inhibit glioma cell proliferation, migration and invasion, as well as promote apoptosis. Further analysis indicated that overexpression of miRNA-320c dramatically led to the G0/G1 phase arrest and correspondingly decreased the percentage of S phase cells by suppressing the expression of G1/S transition key regulators, such as Cyclin D1 and CDK6. Additionally, up-regulation of miRNA-320c could significantly impair migration and invasion of glioma cells via reducing the expression of MMP2, MMP9, N-cadherin and Integrin beta 1. Collectively, our data revealed that miRNA-320c played a crucial role in the carcinoma processes of glioma and might serve as a new prognosis biomarker and therapeutic target of glioma.