Up-regulation of LncRNA MEG3 inhibits cell migration and invasion and enhances cisplatin chemosensitivity in bladder cancer cells

Shu-Qiang Feng, Xiao-Yu Zhang, Hai-Tao Fan, Qi-Jia Sun,  Ming Zhang

Abstract:

It has been proven that maternally expressed 3 (MEG3), a long non-coding RNA (LncRNA), is down-regulated and inversely correlated with prognosis in various types of cancer, including bladder cancer (BC). Nevertheless, the role of MEG3 in BC has not been fully identified. Herein, we found that MEG3 expression was reduced in 21 BC tumor tissue samples compared to corresponding adjacent tissues. We then established T24 and 5637 cells with a stably integrated expression of MEG3 by G418 resistance screening, and data revealed that the BC cells over-expressing MEG3 displayed weaker migration and invasion ability than control cells. The expression and activity of matrix metalloproteinase (MMP)2 and MMP9 were down-regulated when MEG3 was over-expressed. Moreover, MEG3 over-expression sensitized BC cells to the chemotherapy drug cisplatin (DDP). DDP treatment significantly induced cell apoptosis, down-regulated bcl2 expression, and up-regulated cleaved-caspase-3 and bax expression in BC cells with MEG3 over-expression. MEG3 and p53 can also stimulate mutual expression in BC cells, thus indicating a potential positive feedback loop of MEG3 and p53. Our combined results suggest that over-expression of MEG3 inhibits migration and invasion and enhances DDP chemo-sensitivity in bladder cancer cells.