MicroRNA‐16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor‐κB1/MMP9 signaling pathway

Cancer Science

Tian-Quan Yang¹  Xiao-Jun Lu²  Ting-Feng Wu¹  Da-Dong Ding¹  Zhao-Hui Zhao¹  Gui-Lin Chen¹  Xue-Shun Xie¹  Bin Li¹  Yong-Xin Wei¹  Ling-Chuan Guo³  Yu Zhang²  Yu-Lun Huang¹  You-Xin Zhou¹ 

[1] Department of Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China;Department of Neurosurgery, The First People's Hospital of Tai Cang, Suzhou, China;Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China

关键词: Glioma;    miR‐16;    NF‐κB1;    MMP9;    BCL2;   

DOI  :  10.1111/cas.12351

来源: Wiley

【 摘 要 】

Abstract

Recent studies have identified a class of small non-coding RNA molecules, named microRNA (miRNA), that is dysregulated in malignant brain glioblastoma. Substantial data have indicated that miRNA-16 (miR-16) plays a significant role in tumors of various origins. This miRNA has been linked to various aspects of carcinogenesis, including cell apoptosis and migration. However, the molecular functions of miR-16 in gliomagenesis are largely unknown. We have shown that the expression of miR-16 in human brain glioma tissues was lower than in non-cancerous brain tissues, and that the expression of miR-16 decreased with increasing degrees of malignancy. Our data suggest that the expression of miR-16 and nuclear factor (NF)-κB1 was negatively correlated with glioma levels. MicroRNA-16 decreased glioma malignancy by downregulating NF-κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373. Our results also indicated that upregulation of miR-16 promoted apoptosis by suppressing BCL2 expression. Finally, the upregulation of miR-16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness. Taken together, our experiments have validated the important role of miR-16 as a tumor suppressor gene in glioma growth and invasiveness, and revealed a novel mechanism of miR-16-mediated regulation in glioma growth and invasiveness through inhibition of BCL2 and the NF-κB1/MMP-9 signaling pathway. Therefore, our experiments suggest the possible future use of miR-16 as a therapeutic target in gliomas.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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