title: MicroRNA-10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer.
abstract: The present study was performed to investigate the effect of microRNA-10b (miR-10b) on cell migration and invasion in human bladder cancer (BC). Real-time PCR was performed to detect the expression of miR-10b in BC cell lines. miR-10b mimics, the negative control for mimics, miR-10b inhibitor and the negative control for inhibitor were transfected into BC cell lines and the effects of miR-10b on the migration and invasion of cells were investigated through Transwell assay. Meanwhile, protein levels of KLF4, HOXD10, E-cadherin and MMP14 were measured. Luciferase assays were also performed to validate KLF4 and HOXD10 as miR-10b targets. In vivo metastasis assay was performed to validate if miR-10b can promote BC cell line metastasis in vivo. miR-10b is significantly upregulated in BC cell lines and metastatic tissues. Increased miR-10b expression significantly enhanced BC cell migration and invasion, while decreased miR-10b expression reduced cell migration and invasion. In vivo metastasis assay demonstrated that overexpression of miR-10b markedly promoted BC metastasis. Moreover, KLF4 and HOXD10 were identified as direct targets of miR-10b in BC cells. Silencing of KLF4 or HOXD10 recapitulated the pro-metastatic function. Furthermore, we found that E-cadherin and MMP14 may be the downstream factors of KLF4 and HOXD10 in the suppression of BC metastasis by miR-10b. These data suggest that miR-10b may function as oncogenes in BC cells. Targeting these novel strategies, inhibition of miR-10b/KLF4/E-cadherin axis and miR-10b/HOXD10/MMP14 axis may be helpful as a therapeutic approach to block BC cell metastasis.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Gan
authors.initials: G
authors.lastname: Yu
authors.affiliation: Translational Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009857:Oncogenes; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C072064:HOXD10 protein, human