title: The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL.
abstract: MicroRNA-429 (miR-429) has been suggested to inhibit epithelial-mesenchymal transition (EMT), mainly due to targeting of ZEB1 and ZEB2, which are repressors of the cell to cell contact protein, E-cadherin. In this study, we indicated that regulation of miR-429 in cervical cancer cells modulates cell migration, elongation, as well as transforming growth factor β (TGF-β)-induced stress fiber formation through regulating the cytoskeleton reorganization which is likely independent of the zinc finger E-box binding homeobox (ZEB)/E-cadherin axis. ZEB1 and Crk-like adapter protein (CRKL), as novel targets of miR-429 and direct regulators of the actin cytoskeleton were identified. Remarkably, expression levels of ZEB1 and CRKL were inversely associated with the level of miR-429 in cervical cancer cell lines. In addition, individual knockdown and over-expression of these targeting genes phenocopied the roles of miR-429 over-expression and inhibition on cell elongation, migration, stress fiber formation, and invasion. Targeting of ZEB1 by miR-429 led to a decreased expression and transcriptional activity of CRB3, regulated by interference with the translocation of the CRB3. This finally led to decreasing of the expression of Crumbs 3 (CRB3), which is needed for the formation of stress fiber and contractility. Therefore, miR-429 affects cervical cancer by modulating some EMT-related processes. And in this study, evidences were provided to support a role for miR-429 as a novel target suppressing invasion and migration of human cervical cancer cells through modulation of its targeting genes ZEB1 and CRKL. Taken together, our data indicate that miR-429 plays a pivotal role in cervical cancer progression, which is a potential therapeutic target for patients.
authors.affiliation: Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Rd., Zhengzhou 450014, Henan, People's Republic of China. Electronic address: wangwuliang450014@163.com.
authors.forename: Wu-Liang
authors.initials: WL
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071877:Checkpoint Kinase 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D022502:Stress Fibers / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C472002:CRB3 protein, human; C082869:CRKL protein; C546363:MIRN429 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D009687:Nuclear Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: CRKL; Cervical cancer; Invasion; ZEB1; miR-429