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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

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
Authors
Kim, YoungmiPark, DeokbumKim, HyunaChoi, MunseonLee, HansooLee, Yun SilChoe, JongseonKim, Young MyeongJeoung, Dooil
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2013
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
0021-9258JCR Link
Citation
vol. 288, no. 51, pp. 36502 - 36518
Keywords
AngiogenesisAnticancer DrugCancer BiologyInvasionMicroRNAAngiogenic PotentialCAGEFeedback Regulatory LoopTumorigenic PotentialmiR-200b
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Background: The microRNA that regulates the expression of CAGE is unknown. Results: miR-200b and CAGE exert opposite regulations on the response to microtubule-targeting drugs, invasion, tumorigenic potential, and angiogenic potential. Conclusion: CAGE and miR-200b form a feedback regulatory loop. Significance: miR-200b may be a target for the treatment of CAGE-driven cancers. 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 TGF-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.
DOI
10.1074/jbc.M113.502047
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약학대학 > 약학과 > Journal papers
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