miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog pathway factor Gli3

被引:39
作者
Li, Jun [1 ,2 ]
Qiu, Mingxing [1 ,2 ]
An, Yu [1 ,2 ]
Huang, Jianlin [1 ,2 ]
Gong, Chunyu [3 ]
机构
[1] Sichuan Acad Med Sci, Dept Urol, 32 West Second Sect,First Ring Rd, Chengdu 610072, Sichuan, Peoples R China
[2] Sichuan Prov Peoples Hosp, 32 West Second Sect,First Ring Rd, Chengdu 610072, Sichuan, Peoples R China
[3] Sichuan Univ, West China Teaching Hosp 4, Dept Surg, 18 Renmin South Rd, Chengdu 610041, Sichuan, Peoples R China
关键词
miR-7-5p; Gli3; Proliferation; EMT; Bladder cancer; MICRORNA TARGETS; BREAST-CANCER; EXPRESSION; CELLS; GROWTH; METASTASIS; ACTIVATION; SURVIVAL; THERAPY; GENES;
D O I
10.1016/j.bbrc.2018.07.166
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2101 / 2107
页数:7
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