Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1

Abstract The circadian clock confers daily rhythmicity on many biochemical and physiological functions and its disruption is associated with increased risks of developing obesity, diabetes, heart disease and cancer. Although, there are studies on the role of Bmal1 in carcinogenesis using germline, c...

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Autores principales:	Tuba Korkmaz, Fatih Aygenli, Handan Emisoglu, Gozde Ozcelik, Asena Canturk, Secil Yilmaz, Nuri Ozturk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Bmal1 Gene Circadian Clock Genes Bmal1 Knockout Breast Epithelial Cell Line Transcription-translation Feedback Loop (TTFL) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6325aed49fa749149050d389034e30d3
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spelling	oai:doaj.org-article:6325aed49fa749149050d389034e30d32021-12-02T15:08:25ZOpposite Carcinogenic Effects of Circadian Clock Gene BMAL110.1038/s41598-018-34433-42045-2322https://doaj.org/article/6325aed49fa749149050d389034e30d32018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34433-4https://doaj.org/toc/2045-2322Abstract The circadian clock confers daily rhythmicity on many biochemical and physiological functions and its disruption is associated with increased risks of developing obesity, diabetes, heart disease and cancer. Although, there are studies on the role of Bmal1 in carcinogenesis using germline, conditional or tissue-specific knockouts, it is still not well understood how BMAL1 gene affects cancer-related biological events at the molecular level. We, therefore, took an in vitro approach to understand the contribution of BMAL1 in this molecular mechanism using human breast epithelial cell lines by knocking out BMAL1 gene with CRISPR technology. We preferred epithelial cells over fibroblasts as the most of cancers originate from epithelial cells. After obtaining BMAL1 knockouts by targeting the gene at two different sites from non-tumorigenic MCF10A and invasive tumorigenic MDA-MB-231 cells, we analysed apoptosis and invasion properties of the cell lines as representative events in tumor development. BMAL1 disruption sensitized both cell lines to a bulky-DNA adduct forming agent (cisplatin) and a double-strand break-inducing agent (doxorubicin), while it enhanced the invasive properties of MDA-MB-231 cells. These results show that the disruption of clock genes may have opposing carcinogenic effects.Tuba KorkmazFatih AygenliHandan EmisogluGozde OzcelikAsena CanturkSecil YilmazNuri OzturkNature PortfolioarticleBmal1 GeneCircadian Clock GenesBmal1 KnockoutBreast Epithelial Cell LineTranscription-translation Feedback Loop (TTFL)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bmal1 Gene Circadian Clock Genes Bmal1 Knockout Breast Epithelial Cell Line Transcription-translation Feedback Loop (TTFL) Medicine R Science Q
spellingShingle	Bmal1 Gene Circadian Clock Genes Bmal1 Knockout Breast Epithelial Cell Line Transcription-translation Feedback Loop (TTFL) Medicine R Science Q Tuba Korkmaz Fatih Aygenli Handan Emisoglu Gozde Ozcelik Asena Canturk Secil Yilmaz Nuri Ozturk Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
description	Abstract The circadian clock confers daily rhythmicity on many biochemical and physiological functions and its disruption is associated with increased risks of developing obesity, diabetes, heart disease and cancer. Although, there are studies on the role of Bmal1 in carcinogenesis using germline, conditional or tissue-specific knockouts, it is still not well understood how BMAL1 gene affects cancer-related biological events at the molecular level. We, therefore, took an in vitro approach to understand the contribution of BMAL1 in this molecular mechanism using human breast epithelial cell lines by knocking out BMAL1 gene with CRISPR technology. We preferred epithelial cells over fibroblasts as the most of cancers originate from epithelial cells. After obtaining BMAL1 knockouts by targeting the gene at two different sites from non-tumorigenic MCF10A and invasive tumorigenic MDA-MB-231 cells, we analysed apoptosis and invasion properties of the cell lines as representative events in tumor development. BMAL1 disruption sensitized both cell lines to a bulky-DNA adduct forming agent (cisplatin) and a double-strand break-inducing agent (doxorubicin), while it enhanced the invasive properties of MDA-MB-231 cells. These results show that the disruption of clock genes may have opposing carcinogenic effects.
format	article
author	Tuba Korkmaz Fatih Aygenli Handan Emisoglu Gozde Ozcelik Asena Canturk Secil Yilmaz Nuri Ozturk
author_facet	Tuba Korkmaz Fatih Aygenli Handan Emisoglu Gozde Ozcelik Asena Canturk Secil Yilmaz Nuri Ozturk
author_sort	Tuba Korkmaz
title	Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
title_short	Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
title_full	Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
title_fullStr	Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
title_full_unstemmed	Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
title_sort	opposite carcinogenic effects of circadian clock gene bmal1
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6325aed49fa749149050d389034e30d3
work_keys_str_mv	AT tubakorkmaz oppositecarcinogeniceffectsofcircadianclockgenebmal1 AT fatihaygenli oppositecarcinogeniceffectsofcircadianclockgenebmal1 AT handanemisoglu oppositecarcinogeniceffectsofcircadianclockgenebmal1 AT gozdeozcelik oppositecarcinogeniceffectsofcircadianclockgenebmal1 AT asenacanturk oppositecarcinogeniceffectsofcircadianclockgenebmal1 AT secilyilmaz oppositecarcinogeniceffectsofcircadianclockgenebmal1 AT nuriozturk oppositecarcinogeniceffectsofcircadianclockgenebmal1
_version_	1718388124183166976

Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1

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