miR-193 inhibits bladder cancer progression by targeting N-myc

Growing evidence has indicated that miR-193 is involved in the initiation and progression of malignancy, such as bladder cancer, hepatocellular carcinoma, renal cell carcinoma, and colorectal cancer. Nevertheless, the mechanisms of miR-193 in the development of metastatic bladder cancer remains unknown. In the current study, we clarified the association of miR-193/N-myc was implicated in cancer metastasis. miR-193 expression increased in metastatic bladder cancer biopsies compared to the primary cases. Moreover, the elevation of miR-193 was correlated with the invasiveness, lymph node metastasis, and advanced stages of bladder cancer significantly. Downregulation of miR-193 by shRNA hampered proliferation and migration while inducing cell apoptosis. Furthermore, miR-193 sponged N-myc and diminished miR-103 expression. Overexpression of miR-193 released oncogene N-myc expression, leading to the promotion of cell proliferation and migration. Besides, knockout of miR-193 suppressed tumor growth in the human T24 mice models. Briefly, the present findings suggested that miR-193-N-myc were novel promising pathways for conquering bladder cancer progression. Bladder cancer samples and the adjacent tissues were recruited in the present study. Microarray-based miRNA expression profiles were obtained with Qiagen custom miScript miRNA PCR Arrays.

越来越多的证据表明，miR-193（microRNA-193）参与了恶性肿瘤的发生与进展，涵盖膀胱癌、肝细胞癌、肾细胞癌及结直肠癌等多种类型。然而，miR-193在转移性膀胱癌发生发展中的具体机制仍未明确。本研究阐明了miR-193与N-myc的调控轴在肿瘤转移中的关联：与原发性膀胱癌组织相比，转移性膀胱癌活检样本中miR-193的表达水平显著升高；且miR-193的表达上调与膀胱癌的侵袭性、淋巴结转移及临床分期进展显著相关。通过短发夹RNA（shRNA，short hairpin RNA）下调miR-193的表达，可抑制肿瘤细胞的增殖与迁移，并诱导细胞凋亡。进一步研究发现，miR-193可通过海绵吸附作用靶向调控N-myc，并降低miR-103的表达水平；而过表达miR-193可上调癌基因N-myc的表达，进而促进细胞增殖与迁移。此外，在人膀胱癌T24细胞小鼠模型中，敲除miR-193可抑制肿瘤生长。综上，本研究结果表明，miR-193-N-myc调控轴是有望干预膀胱癌进展的全新潜在靶点通路。本研究纳入了膀胱癌样本及其癌旁正常组织，采用Qiagen定制化miScript miRNA聚合酶链式反应（PCR，polymerase chain reaction）芯片获取了基于微阵列的miRNA表达谱数据。