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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 459 - 468 (10page)
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초록· 키워드
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Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.
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참고문헌 (42)
참고문헌 신청
Altman, B. J. / 2015 / MYC disrupts the circadian clock and metabolism in cancer cells / Cell Metab 22:1009~1019
Bailey, A. M. / 2014 / FXR silencing in human colon cancer by DNA methylation and KRAS signaling / Am. J. Physiol. Gastrointest. Liver Physiol 306:G48~G58
Bonamy, C. / 2018 / Expression of the human antimicrobial peptide beta-defensin-1 is repressed by the EGFR-ERK-MYC axis in colonic epithelial cells / Sci. Rep 8:18043
Cancer Genome Atlas Network / 2012 / Comprehensive molecular characterization of human colon and rectal cancer / Nature 487:330~337
Cao, Z. / 2011 / MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase / Cancer Res 71:2286~2297
Bailey, A. M. / 2014 / FXR silencing in human colon cancer by DNA methylation and KRAS signaling / Am. J. Physiol. Gastrointest. Liver Physiol 306:G48~G58
Bonamy, C. / 2018 / Expression of the human antimicrobial peptide beta-defensin-1 is repressed by the EGFR-ERK-MYC axis in colonic epithelial cells / Sci. Rep 8:18043
Cancer Genome Atlas Network / 2012 / Comprehensive molecular characterization of human colon and rectal cancer / Nature 487:330~337
Cao, Z. / 2011 / MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase / Cancer Res 71:2286~2297
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