USP30-AS1 通过 NF-κB/MYBBP1A 信号抑制结肠癌细胞的炎症反应

IF 4.5 2区 医学 Q2 CELL BIOLOGY
Ruonan Wang, Xiaolin Li, Yapei Jiang, Haowei Zhang, Shiyue Yang, Weidong Xie, Naihan Xu
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引用次数: 0

摘要

结肠直肠癌(CRC)是全球最常见的恶性肿瘤之一,对人类健康构成严重威胁。最近的研究强调了长非编码 RNA(lncRNA)的异常表达在 CRC 的发生和发展中的关键作用。在这项研究中,我们发现 lncRNA USP30-AS1 在结直肠癌组织中显著下调,尤其是在疾病的晚期阶段。这种下调与患者生存率的降低有关。与 USP30-AS1 相关基因的富集分析表明,USP30-AS1 与炎症反应密切相关。值得注意的是,包括脂多糖(LPS)和肿瘤坏死因子-α(TNF-α)在内的促炎刺激会上调 USP30-AS1 的表达。功能测试表明,敲除 USP30-AS1 会导致 IκBα 蛋白降解增加、NF-κB 转录活性增强以及 NF-κB 下游炎症分子(包括 NLRP3、IL-1β 和 IL-18)表达水平升高。相反,异位表达 USP30-AS1 可抑制 NF-κB 的转录活化。从机理上讲,USP30-AS1 与 MYBBP1A 相互作用,MYBBP1A 是已知的 NF-κB 信号转导调节因子。值得注意的是,过表达 MYBBP1A 可减轻 USP30-AS1 敲除对 NF-κB 激活的刺激作用。总之,这些研究结果表明,USP30-AS1通过调节MYBBP1A/NF-κB信号通路抑制结直肠癌细胞的生长,从而凸显出USP30-AS1是治疗结直肠癌的潜在新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
USP30-AS1 Suppresses Colon Cancer Cell Inflammatory Response Through NF-κB/MYBBP1A Signaling.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and poses a significant threat to human health. Recent studies have underscored the crucial role of aberrant expression of long non-coding RNAs (lncRNAs) in the initiation and progression of CRC. In this study we identified that lncRNA USP30-AS1 is significantly downregulated in colorectal cancer tissues, particularly in the advanced stages of the disease. This downregulation correlates with reduced survival rates among patients. Enrichment analysis of genes associated with USP30-AS1 indicates a strong association with inflammatory responses. Notably, pro-inflammatory stimuli, including lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α), were found to upregulate the expression of USP30-AS1. Functional assays demonstrated that the knockdown of USP30-AS1 resulted in increased degradation of IκBα protein and enhanced NF-κB transcriptional activity, as well as elevated expression levels of NF-κB downstream inflammatory molecules, including NLRP3, IL-1β, and IL-18. Conversely, ectopic expression of USP30-AS1 inhibited NF-κB transactivation. Mechanistically, USP30-AS1 interacts with MYBBP1A, a known regulator of NF-κB signaling. Notably, overexpression of MYBBP1A alleviated the stimulatory effect of USP30-AS1 knockdown on NF-κB activation. Collectively, these findings suggest that USP30-AS1 acts as a suppressor of colorectal cancer cell growth by modulating the MYBBP1A/NF-κB signaling pathway, thereby highlighting USP30-AS1 as a potential novel therapeutic target for colorectal cancer treatment.

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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