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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.6
- 수록면
- 562 - 572 (11page)
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We previously reported the role of histone deacetylase 3 (HDAC3) in response to anti-cancer drugs. The decreased expression of HDAC3 in anti-cancer drug-resistant cancer cell line is responsible for the resistance to anti-cancer drugs. In this study, we investigated molecular mechanisms associated with regulation of HDAC3 expression.
MG132, an inhibitor of proteasomal degradation, induced the expression of HDAC3 in various anti-cancer drugresistant cancer cell lines. Ubiquitination of HDAC3 was observed in various anti-cancer drug-resistant cancer cell lines. HDAC3 showed an interaction with SIAH2, an ubiquitin E3 ligase, that has increased expression in various anticancer drug-resistant cancer cell lines. miRNA array analysis showed the decreased expression of miR-335 in these cells. Targetscan analysis predicted the binding of miR-335 to the 3 -UTR of SIAH2. miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anticancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR- 335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs.
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참고문헌 (58)
참고문헌 신청
Asuthkar, S. / 2012 / Epigenetic regulation of miRNA-211 by MMP-9 governs glioma cell apoptosis, chemosensitivity and radiosensitivity / Oncotarget 3:1439~1454
Bardai, F. H. / 2011 / Selective toxicity by HDAC3in neurons : regulation by Akt and GSK3beta / J. Neurosci 31:1746~1751
Calin, G. A. / 2006 / MicroRNA signatures in human cancers / Nat. Rev. Cancer 6:857~866
Cao, J. / 2013 / miR-335 represents an invasion suppressor gene in ovarian cancer by targeting Bcl-w / Oncol Rep 30:701~706
Chan, P. / 2011 / The expression of the ubiquitin ligase SIAH2(seven in absentia homolog 2)is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression / Breast Cancer Res 13:19
Bardai, F. H. / 2011 / Selective toxicity by HDAC3in neurons : regulation by Akt and GSK3beta / J. Neurosci 31:1746~1751
Calin, G. A. / 2006 / MicroRNA signatures in human cancers / Nat. Rev. Cancer 6:857~866
Cao, J. / 2013 / miR-335 represents an invasion suppressor gene in ovarian cancer by targeting Bcl-w / Oncol Rep 30:701~706
Chan, P. / 2011 / The expression of the ubiquitin ligase SIAH2(seven in absentia homolog 2)is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression / Breast Cancer Res 13:19
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