Department of Urology, Beijing Friendship Hospital Affiliated to Capital Medical University, China.
FEBS J. 2013 Sep;280(18):4531-8. doi: 10.1111/febs.12417. Epub 2013 Jul 25.
microRNAs (miRNAs) have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Wnt signaling plays an important role in the regulation of tumorigenesis and cancer progression. However, little is known about whether miR-144 regulates bladder cancer cell proliferation by controlling Wnt signaling. In this study, we found that the miR-144 expression level is significantly decreased in bladder cancer cell lines as well as in clinical cancer tissues. miR-144 inhibitor blocks the expression of endogenous miR-144 and promotes cancer cell proliferation, whereas miR-144 overexpression is sufficient to inhibit cell proliferation. We further demonstrated that enhancer of zeste homolog 2 (EZH2) is a target gene of miR-144. miR-144 downregulation relieves miR-144-mediated repression of EZH2, which results in activation of Wnt/β-catenin signaling and subsequent cell proliferation. These data suggest miR-144 is an essential mediator of bladder cancer cell proliferation, thus offering a new target for the development of therapeutic agents against bladder cancer.
microRNAs (miRNAs) 被认为是转录调控、细胞生长和肿瘤发生等多种生物学过程的关键调节因子。Wnt 信号通路在肿瘤发生和癌症进展的调控中起着重要作用。然而，miR-144 是否通过控制 Wnt 信号通路来调节膀胱癌细胞增殖还知之甚少。在本研究中，我们发现 miR-144 的表达水平在膀胱癌细胞系以及临床癌症组织中均显著降低。miR-144 抑制剂阻断内源性 miR-144 的表达并促进癌细胞增殖，而 miR-144 过表达足以抑制细胞增殖。我们进一步证明，EZH2 是 miR-144 的靶基因。miR-144 的下调解除了 miR-144 对 EZH2 的抑制，导致 Wnt/β-catenin 信号通路的激活和随后的细胞增殖。这些数据表明 miR-144 是膀胱癌细胞增殖的重要介质，为开发治疗膀胱癌的药物提供了新的靶点。
