Peng Yang, Dong Wen, Lin Tian-Xin, Zhong Guang-Zheng, Liao Bei, Wang Bo, Gu Peng, Huang Li, Xie Yun, Lu Fu-Ding, Chen Xu, Xie Wei-Bin, He Wang, Wu Shao-Xu, Huang Jian
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, SunYat-Sen Memorial Hospital, SunYat-Sen University, Guangzhou, People's Republic of China.
Oncotarget. 2015 Jun 30;6(18):16043-58. doi: 10.18632/oncotarget.3755.
MicroRNA-155 (miR-155) is dysregulated in human cancers. In this study, we reported that miR-155 was over-expressed in bladder cancer tissues. We found that miR-155 promoted cell proliferation in vitro and tumorigenesis in vivo. MiR-155 directly reduced the expression of the tumor suppressor DMTF1. The expression of DMTF1 was decreased in bladder cancer tissues. Similar to the restoring miR-155 expression, knockdown of DMTF1 promoted cell growth and cell cycle progression, whereas DMTF1 over-expression rescued the effect of miR-155. Moreover, we investigated DMTF1-Arf-p53 pathway and found that DMTF1 worked in both p53-dependent and p53-independent manners. Taken together, our findings suggested that miR-155 functions as a tumor promoter in bladder cancer, which is partially through repressing DMTF1 expression. The identification of miR-155 and its novel target DMTF1 will be valuable in developing diagnostic markers and therapeutic applications for bladder cancer.
微小RNA-155（miR-155）在人类癌症中表达失调。在本研究中，我们报道miR-155在膀胱癌组织中过度表达。我们发现miR-155在体外促进细胞增殖，在体内促进肿瘤发生。miR-155直接降低肿瘤抑制因子DMTF1的表达。DMTF1在膀胱癌组织中的表达降低。与恢复miR-155表达相似，敲低DMTF1可促进细胞生长和细胞周期进程，而DMTF1过表达可挽救miR-155的作用。此外，我们研究了DMTF1-Arf-p53通路，发现DMTF1以p53依赖和p53非依赖的方式发挥作用。综上所述，我们的研究结果表明，miR-155在膀胱癌中作为肿瘤促进因子发挥作用，部分是通过抑制DMTF1的表达。miR-155及其新靶点DMTF1的鉴定对于开发膀胱癌的诊断标志物和治疗应用具有重要价值。
