miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog pathway factor Gli3
miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog pathway factor Gli3
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DOI：
10.1016/j.bbrc.2018.07.166
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发表时间：
2018-09-10
影响因子：
3.1
通讯作者：
Gong, Chunyu
中科院分区：
文献类型：
--
作者：
Li, Jun;Qiu, Mingxing;Gong, Chunyu
尽管膀胱癌的诊断和治疗已取得重要进展，但晚期膀胱癌患者的总体生存率仍然很低。因此，有必要对膀胱癌发生发展的分子机制进行深入研究.根据以往的报道，微小RNA（miRNAs）可以通过靶向其下游mRNA来调控肿瘤的发生。本研究旨在探索和分析一种新的可调控膀胱癌进展的miRNA-mRNA轴。基于微阵列分析，发现182个mRNA在BCa组织中上调。基因肿瘤学（GO）分析和京都基因和基因组百科全书（KEGG）分析表明，这些上调的mRNA与刺猬途径相关。Hedgehog通路的重要因子Gli 3就属于这182个上调的mRNA。因此，选择Gli 3进行进一步研究。Kaplan-Meier分析显示Gli 3高表达预示BCa患者预后不良。功能实验结果表明，沉默的Gli 3对细胞增殖，迁移和EMT进程的抑制作用。从机制上讲，Gli 3是BCa细胞中miR-7- 5 p的靶mRNA。最后，进行拯救测定以验证miR-7- 5 p/Gli 3轴在BCa进展中的特异性功能。根据所有数据，我们得出结论，miR-7- 5 p通过下调Gli 3在BCa中起到肿瘤抑制剂的作用。(C)2018由Elsevier Inc.出版
Although important progresses have been made in the diagnosis and treatment of bladder cancer (BCa), the overall survival for patients with advanced BCa remains poor. It is necessary to uncover the molecular mechanism underlying the initiation and progression of bladder cancer. According to previous reports, mircoRNAs (miRNAs) can regulate tumorigenesis by targeting their downstream mRNAs. This study aims to explore and analyze a novel miRNA-mRNA axis which can regulate the progression of bladder cancer. Based on the microarray analysis, 182 mRNAs were found to be upregulated in BCa tissues. Gene oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these upregulated mRNAs are related with hedgehog pathway. Gli3, an important factor of hedgehog pathway, belongs to these 182 upregulated mRNAs. Therefore, Gli3 was chosen to do further study. Kaplan-Meier analysis revealed that highly expressed Gli3 predicted unfavorable prognosis for patients with BCa. Results of functional experiments indicated the inhibitory effects of silenced Gli3 on cell proliferation, migration and EMT progress. Mechanically, Gli3 was the target mRNA of miR-7-5p in BCa cells. Finally, rescue assays were performed to validate the specific function of miR-7-5p/Gli3 axis in BCa progression. According to all data, we concluded that miR-7-5p acts as a tumor suppressor in BCa by downregulating Gli3. (C) 2018 Published by Elsevier Inc.