Deficiency of BTB and CNC Homology 1 promotes colon tumorigenesis by enhancing intestinal epithelial cell proliferation in mice.

IF 1.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioscience, Biotechnology, and Biochemistry Pub Date : 2025-05-19 DOI:10.1093/bbb/zbaf073

Karen Kanamaru, Jun Tanikawa, Tomohisa Takagi, Akihiko Muto, Kazuhiko Igarashi, Yuji Naito, Yasuki Higashimura

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引用次数: 0

Abstract

Intestinal epithelial cells serve as the frontline of host defense and function as a physical barrier. BTB and CNC homology 1 (Bach1) is a transcriptional repressor involved in gastrointestinal physiology, but its role in epithelial proliferation and colorectal tumorigenesis remains unclear. This study demonstrates that Bach1 deficiency promotes colonic epithelial proliferation and enhances colorectal tumorigenesis. In Bach1-deficient (Bach1-/-) mice, structural analysis revealed elongation of villi in the small intestine and pronounced changes in the colon, with increased Ki67+ and BrdU+ cells indicating hyperproliferation. In HT-29 colon cancer cells, BACH1 knockdown accelerated cell cycle progression by reducing G0/G1-phase cells and increasing S-phase and G2/M-phase cells, accompanied by upregulation of cell cycle-related genes. Additionally, in an azoxymethane-induced colorectal carcinogenesis model, Bach1-/- mice exhibited a significant increase in aberrant crypt foci formation. These findings suggest that Bach1 deficiency contributes to colorectal tumorigenesis by promoting epithelial hyperproliferation.

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BTB和CNC同源物1缺乏通过增强小鼠肠上皮细胞增殖促进结肠肿瘤的发生。

肠上皮细胞是宿主防御的第一线，起着物理屏障的作用。BTB和CNC同源1 （Bach1）是一种参与胃肠道生理的转录抑制因子，但其在上皮细胞增殖和结直肠肿瘤发生中的作用尚不清楚。本研究表明，Bach1缺乏可促进结肠上皮细胞增殖，促进结直肠肿瘤的发生。在Bach1缺陷（Bach1-/-）小鼠中，结构分析显示小肠绒毛伸长，结肠发生明显变化，Ki67+和BrdU+细胞增加表明过度增殖。在HT-29结肠癌细胞中，BACH1敲低可通过减少G0/ g1期细胞，增加s期和G2/ m期细胞来加速细胞周期进程，并伴有细胞周期相关基因的上调。此外，在偶氮甲烷诱导的结直肠癌模型中，Bach1-/-小鼠表现出异常隐窝灶形成的显著增加。这些发现表明，Bach1缺乏通过促进上皮细胞的过度增生而促进结直肠肿瘤的发生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioscience, Biotechnology, and Biochemistry 生物-生化与分子生物学

CiteScore

3.50

自引率

0.00%

发文量

183

审稿时长

1 months

期刊介绍： Bioscience, Biotechnology, and Biochemistry publishes high-quality papers providing chemical and biological analyses of vital phenomena exhibited by animals, plants, and microorganisms, the chemical structures and functions of their products, and related matters. The Journal plays a major role in communicating to a global audience outstanding basic and applied research in all fields subsumed by the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA).