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LRP11-AS1通过miR-149-3p/CDK4途径介导脆弱拟杆菌肠毒素相关的结直肠癌发生。

LRP11-AS1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal Cancer via the miR-149-3p/CDK4 pathway.

作者信息

Wu Zhongguang, Yu Mengqiu, Zeng Yu, Huang Yingfeng, Zheng Weidong

机构信息

Department of Laboratory Medicine, Shenzhen University General Hospital, Shenzhen, China.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Health Science Center, Shenzhen University, Shenzhen, China.

出版信息

Cancer Gene Ther. 2025 Feb;32(2):184-197. doi: 10.1038/s41417-024-00862-9. Epub 2024 Dec 13.

Abstract

Long noncoding RNAs (lncRNAs) are critical in tumorigenesis and show potential for tumor diagnosis and therapy. Enterotoxigenic Bacteroides fragilis (ETBF), known for producing enterotoxins, is implicated in human gut tumorigenesis, yet the underlying mechanisms are not fully elucidated. This study aims to clarify the molecular mechanisms by which lncRNAs contribute to ETBF-induced tumorigenesis, with a focus on LRP11-AS1's role in modulating ETBF's colorectal carcinogenesis. We found a marked increase in LRP11-AS1 expression in colorectal cancer (CRC) tissues compared to adjacent non-tumorous tissues. In vitro, CRC cells exposed to ETBF showed elevated LRP11-AS1 levels. Mechanistically, LRP11-AS1 was shown to enhance CDK4 expression by competitively binding to miR-149-3p. These results indicate that LRP11-AS1 may facilitate ETBF-related carcinogenesis in CRC and could serve as a therapeutic target and diagnostic biomarker for ETBF-associated CRC.

摘要

长链非编码RNA(lncRNAs)在肿瘤发生过程中至关重要,并且在肿瘤诊断和治疗方面显示出潜力。产肠毒素脆弱拟杆菌(ETBF)以产生肠毒素而闻名,与人类肠道肿瘤发生有关,但其潜在机制尚未完全阐明。本研究旨在阐明lncRNAs促进ETBF诱导的肿瘤发生的分子机制,重点关注LRP11-AS1在调节ETBF相关结直肠癌发生中的作用。我们发现,与相邻的非肿瘤组织相比,结直肠癌(CRC)组织中LRP11-AS1的表达显著增加。在体外,暴露于ETBF的CRC细胞显示LRP11-AS1水平升高。从机制上讲,LRP11-AS1通过竞争性结合miR-149-3p来增强CDK4的表达。这些结果表明,LRP11-AS1可能促进CRC中ETBF相关的致癌作用,并可作为ETBF相关CRC的治疗靶点和诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a8/11839468/5e36ae6426ce/41417_2024_862_Fig1_HTML.jpg

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