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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, Youngmi; Park, Deokbum; Kim, Hyuna; Choi, Munseon; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil
- Ewha Authors
- 이윤실
- SCOPUS Author ID
- 이윤실
- Issue Date
- 2013
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- ISSN
- 0021-9258
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY vol. 288, no. 51, pp. 36502 - 36518
- Keywords
- Angiogenesis; Anticancer Drug; Cancer Biology; Invasion; MicroRNA; Angiogenic Potential; CAGE; Feedback Regulatory Loop; Tumorigenic Potential; miR-200b
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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