Xiu Youcheng, Liu Zan, Xia Shunyao, Jin Chengjun, Yin Huaifu, Zhao Weiming, Wu Qiong
School of Life Science and Biotechnology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, China; Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
PLoS One. 2014 Oct 16;9(10):e109734. doi: 10.1371/journal.pone.0109734. eCollection 2014.
There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3'-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer.
越来越多的证据表明,某些微小RNA(miRNA)的失调可能促进肿瘤进展和转移,并被认为是转录调控、细胞生长和肿瘤发生等多种生物学过程的关键调节因子。先前的研究表明,miR-137在一些恶性肿瘤中表达失调,但其在膀胱癌中的作用仍不清楚。在我们的研究中,我们发现miR-137在人膀胱癌组织和细胞系中上调。此外,在临床膀胱癌患者中,较高水平的miR-137与pM或pTNM分期相关。在膀胱癌细胞中强制表达miR-137可显著增强其增殖、迁移和侵袭能力。生物信息学分析确定肿瘤抑制基因PAQR3为潜在的miR-137靶基因。进一步研究表明,miR-137通过与其3'-非翻译区结合抑制PAQR3的表达。用小干扰RNA沉默PAQR3可模拟miR-137过表达的效果,而在过表达miR-137的膀胱癌细胞中恢复PAQR3的表达,可部分逆转miR-137的抑制作用。这些发现表明,miR-137可能是膀胱癌中的一个潜在癌基因。