Enterotoxigenic Bacteroides fragilis induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B.

Gut Microbes
Qian-Qian LiuJing-Yuan Fang

Abstract

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xeno...Continue Reading

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Citations

Dec 18, 2020·Frontiers in Cell and Developmental Biology·Zheng ZhouMeng Bian
Jul 30, 2021·Critical Reviews in Food Science and Nutrition·Yiqiu FeiMingfei Yao

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Methods Mentioned

BETA
xenograft
PCR
transfection
ChIP
Protein Assay
immunoprecipitation
Assay

Software Mentioned

GraphPad
PrimerBank
Image J
extreme limiting dilution analysis ( ELDA )
GraphPad Prism6

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