Details

Autor(en) / Beteiligte

• Yang, Tian‐Quan
• Lu, Xiao‐Jun
• Wu, Ting‐Feng
• Ding, Da‐Dong
• Zhao, Zhao‐Hui
• Chen, Gui‐Lin
• Xie, Xue‐Shun
• Li, Bin
• Wei, Yong‐Xin
• Guo, Ling‐Chuan
• Zhang, Yu
• Huang, Yu‐Lun
• Zhou, You‐Xin
• Du, Zi‐Wei

Titel

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

Ist Teil von

• Cancer science, 2014-03, Vol.105 (3), p.265-271

Ort / Verlag

England: BlackWell Publishing Ltd

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. We first report that miR‐16 and NF‐κB1expression were inversely correlated to glioma levels in the same patient samples. We further identified the miR‐16 as a negative regulator of tumor growth and invasion, both in vitro and in vivo. Mechanistically the tumor‐suppressive role of miR‐16 can be attributed to inhibition of BCL‐2 and NF‐kappaB1/MMP9 signaling pathways.