Department of Urology, The Second Hospital of Jilin University, Changchun, China.
Neoplasma. 2018 Nov 15;65(6):925-932. doi: 10.4149/neo_2018_180125N55. Epub 2018 Jun 18.
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.
已经证实,母系表达基因 3(MEG3)是一种长链非编码 RNA(lncRNA),在包括膀胱癌(BC)在内的各种类型的癌症中表达下调且与预后呈负相关。然而,MEG3 在 BC 中的作用尚未完全确定。在此,我们发现与相应的相邻组织相比,21 例 BC 肿瘤组织样本中的 MEG3 表达降低。然后,我们通过 G418 抗性筛选建立了稳定整合 MEG3 表达的 T24 和 5637 细胞,数据显示,过表达 MEG3 的 BC 细胞的迁移和侵袭能力弱于对照细胞。当过表达 MEG3 时,基质金属蛋白酶(MMP)2 和 MMP9 的表达和活性下调。此外,过表达 MEG3 可使 BC 细胞对化疗药物顺铂(DDP)敏感。DDP 处理可显著诱导过表达 MEG3 的 BC 细胞凋亡,下调 bcl2 表达,上调 cleaved-caspase-3 和 bax 表达。MEG3 和 p53 也可以在 BC 细胞中刺激相互表达,从而表明 MEG3 和 p53 之间存在潜在的正反馈回路。我们的综合结果表明,过表达 MEG3 可抑制膀胱癌细胞的迁移和侵袭,并增强 DDP 化疗敏感性。