长链非编码 RNA miR143HG 通过调节 miR-1275/AXIN2 轴抑制膀胱癌的发展,从而使 Wnt/β-连环蛋白途径失活。
LncRNA miR143HG suppresses bladder cancer development through inactivating Wnt/β-catenin pathway by modulating miR-1275/AXIN2 axis.
机构信息
Department of Urology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
First Clinical College, Southern Medical University, Guangzhou, China.
出版信息
J Cell Physiol. 2019 Jul;234(7):11156-11164. doi: 10.1002/jcp.27764. Epub 2018 Nov 23.
Although increasing long noncoding RNAs (lncRNAs) have been identified by high-throughput sequencing, their functions in human cancer remain largely unknown. The function of lncRNA miR143HG has not been explored before. In the present study, we found that miR143HG expression was significantly downregulated in bladder cancer tissues (BCa) compared with normal tissues. We showed that miR143HG high expression was associated with a high survival rate in BCa patients. Gain-of-function assays demonstrated that miR143HG overexpression suppressed the proliferation, arrested cell cycle progression, and attenuated migration and invasion of BCa cells in vitro. In vivo assay illustrated that ectopic expression of miR143HG inhibited BCa growth in vivo. Mechanistically, miR143HG was identified to inhibit the level of miR-1275, whereas miR-1275 directly targeted AXIN2, a negative regulator of the Wnt/β-catenin pathway. Restoration of miR-1275 or knockdown of AXIN2 significantly rescued the proliferation, migration, and invasion abilities of BCa cells. In summary, our findings demonstrated that miR143HG/miR-1275/AXIN2 axis regulates BCa development by modulating the Wnt/β-catenin pathway.
虽然高通量测序已经鉴定出越来越多的长链非编码 RNA(lncRNA),但其在人类癌症中的功能仍知之甚少。lncRNA miR143HG 的功能以前尚未被探索过。在本研究中,我们发现 miR143HG 在膀胱癌组织(BCa)中的表达明显低于正常组织。我们表明,miR143HG 高表达与 BCa 患者的高生存率相关。功能获得性实验表明,miR143HG 过表达可抑制体外 BCa 细胞的增殖、细胞周期进程停滞,并减弱迁移和侵袭。体内实验表明,miR143HG 的异位表达可抑制体内 BCa 的生长。从机制上讲,miR143HG 被鉴定为抑制 miR-1275 的水平,而 miR-1275 直接靶向 Wnt/β-catenin 通路的负调节剂 AXIN2。miR-1275 的恢复或 AXIN2 的敲低显著挽救了 BCa 细胞的增殖、迁移和侵袭能力。总之,我们的研究结果表明,miR143HG/miR-1275/AXIN2 轴通过调节 Wnt/β-catenin 通路调节 BCa 的发展。