Squalene epoxidase drives cancer cell proliferation and promotes gut dysbiosis to accelerate colorectal carcinogenesis

ObjectiveAberrant lipid metabolism is a hallmark of colorectal cancer (CRC). Squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol biosynthesis, is upregulated in CRC. Here, we aim to determine oncogenic function of SQLE and its interplay with gut microbiota in promoting colorectal tumour...

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Veröffentlicht in:	Gut 2022-11, Vol.71 (11), p.2253-2265
Hauptverfasser:	Li, Chuangen, Wang, Yong, Liu, Dabin, Wong, Chi Chun, Coker, Olabisi Oluwabukola, Zhang, Xiang, Liu, Changan, Zhou, Yunfei, Liu, Yali, Kang, Wei, To, Ka Fai, Sung, Joseph JY, Yu, Jun
Format:	Artikel
Sprache:	eng
Schlagworte:	5-Fluorouracil Animal models Apoptosis Azoxymethane Bacteria Bile acids Cancer therapies Carcinogenesis CDX2 protein Cell cycle Cell growth Cell proliferation Chemotherapy Cholesterol Colon colonic microflora Colorectal cancer Colorectal carcinoma colorectal neoplasm Drug resistance Dysbacteriosis Gene expression Genomes Germfree Intestinal microflora Lipid metabolism Lipids Low income groups Medical prognosis Metabolism Metabolomics Metastasis Microbiota Mortality Oxaliplatin Pathogenesis Patients Permeability Rodents Squalene Squalene epoxidase Surgery Terbinafine Transgenic animals Transgenic mice Transplantation Tumorigenesis Tumors
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Zusammenfassung:	ObjectiveAberrant lipid metabolism is a hallmark of colorectal cancer (CRC). Squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol biosynthesis, is upregulated in CRC. Here, we aim to determine oncogenic function of SQLE and its interplay with gut microbiota in promoting colorectal tumourigenesis.DesignPaired adjacent normal tissues and CRC from two cohorts were analysed (n=202). Colon-specific Sqle transgenic (Sqle tg) mice were generated by crossing Rosa26-lsl-Sqle mice to Cdx2-Cre mice. Stools were collected for metagenomic and metabolomic analyses.ResultsSQLE messenger RNA and protein expression was upregulated in CRC (p
ISSN:	0017-5749 1468-3288
DOI:	10.1136/gutjnl-2021-325851