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miRNA-320c 的下调促进人脑胶质瘤的生长和转移,并预测其预后不良。

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

机构信息

Department of Science and Education, Jiangxi Key Laboratory of Translational Cancer Research, Jiangxi Cancer Hospital, Nanchang, Jiangxi, 330029, PR China.

Department of Pharmacy, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, 330029, PR China.

出版信息

Brain Res Bull. 2018 May;139:125-132. doi: 10.1016/j.brainresbull.2018.02.009. Epub 2018 Feb 10.

Abstract

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 β1. 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.

摘要

新兴研究表明,失调的 miRNA 与多种癌症的肿瘤发生和进展有关。miRNA-320c 是 miRNA-320 家族的重要成员,其特征是一种新的候选 miRNA,可抑制结直肠癌和膀胱癌的发展。然而,miRNA-320c 在人胶质瘤中的功能尚不清楚。在这里,我们发现 miRNA-320c 在胶质瘤组织中明显下调,与正常脑组织相比,通过 qRT-PCR 与胶质瘤的临床分期密切相关。此外,Kaplan-Meier 分析表明,miRNA-320c 低表达的患者生存期较短。多变量 Cox 回归分析表明,miRNA-320c 可作为胶质瘤患者的独立预后不良因素。功能上,miRNA-320c 的过表达可显著抑制胶质瘤细胞的增殖、迁移和侵袭,并促进凋亡。进一步分析表明,miRNA-320c 的过表达通过抑制 G1/S 转换关键调节因子(如 Cyclin D1 和 CDK6)的表达,导致 G0/G1 期阻滞,并相应降低 S 期细胞的百分比。此外,miRNA-320c 的上调可通过降低 MMP2、MMP9、N-钙粘蛋白和整合素 β1 的表达显著抑制胶质瘤细胞的迁移和侵袭。总之,我们的数据表明 miRNA-320c 在胶质瘤的癌过程中发挥着重要作用,可能成为胶质瘤的新预后生物标志物和治疗靶点。

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