title: miR-200b and cancer/testis antigen CAGE form a feedback loop to regulate the invasion and tumorigenic and angiogenic responses of a cancer cell line to microtubule-targeting drugs.
abstract: Cancer/testis antigen cancer-associated gene (CAGE) is known to be involved in various cellular processes, such as proliferation, cell motility, and anti-cancer drug resistance. However, the mechanism of the expression regulation of CAGE remains unknown. Target scan analysis predicted the binding of microRNA-200b (miR-200b) to CAGE promoter sequences. The expression of CAGE showed an inverse relationship with miR-200b in various cancer cell lines. miR-200b was shown to bind to the 3'-UTR of CAGE and to regulate the expression of CAGE at the transcriptional level. miR-200b also enhanced the sensitivities to microtubule-targeting drugs in vitro. miR-200b and CAGE showed opposite regulations on invasion potential and responses to microtubule-targeting drugs. Xenograft experiments showed that miR-200b had negative effects on the tumorigenic and metastatic potential of cancer cells. The effect of miR-200b on metastatic potential involved the expression regulation of CAGE by miR-200b. miR-200b decreased the tumorigenic potential of a cancer cell line resistant to microtubule-targeting drugs in a manner associated with the down-regulation of CAGE. ChIP assays showed the direct regulation of miR-200b by CAGE. CAGE enhanced the invasion potential of a cancer cell line stably expressing miR-200b. miR-200b exerted a negative regulation on tumor-induced angiogenesis. The down-regulation of CAGE led to the decreased expression of plasminogen activator inhibitor-1, a TGFβ-responsive protein involved in angiogenesis, and VEGF. CAGE mediated tumor-induced angiogenesis and was necessary for VEGF-promoted angiogenesis. Human recombinant CAGE protein displayed angiogenic potential. Thus, miR-200b and CAGE form a feedback regulatory loop and regulate the response to microtubule-targeting drugs, as well as the invasion, tumorigenic potential, and angiogenic potential.
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.forename: Hyuna
authors.initials: H
authors.lastname: Kim
authors.forename: Munseon
authors.initials: M
authors.lastname: Choi
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
authors.forename: Young Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D002645:Chickens; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D050257:Tubulin Modulators; D042461:Vascular Endothelial Growth Factor A; C454199:DDX53 protein, human; D053487:DEAD-box RNA Helicases
keywords: Angiogenesis; Angiogenic Potential; Anticancer Drug; CAGE; Cancer Biology; Feedback Regulatory Loop; Invasion; MicroRNA; Tumorigenic Potential; miR-200b