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由circMAP3K13编码的MAP3K13-232aa通过直接结合胃腺癌中的IKKα增强顺铂诱导的细胞焦亡。

MAP3K13-232aa encoded by circMAP3K13 enhances cisplatin-induced pyroptosis by directly binding to IKKα in gastric adenocarcinoma.

作者信息

Du Kaining, Zhang Xiaojing, Qin Ying, Ma Huizhen, Bing Chuhan, Deng Shiqi, Chen Yang, Qin Jiequan, Chang Shanshan, Xiao Siyu, Peng Lehua, Xie Xiaoya, Feng Xianling, Fu Xianli, Wei Yanjie, Fan Xinmin, Ashktorab Hassan, Smoot Duane, Jin Zhe, Peng Yin

机构信息

Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, PR China.

出版信息

Cell Death Dis. 2025 Sep 1;16(1):667. doi: 10.1038/s41419-025-07991-5.

Abstract

Gastric cancer (GC) is one of the most common and lethal malignancies in developing countries, with particularly high prevalence in China. Circular RNAs (circRNAs) have garnered increasing attention for their roles in disease pathogenesis. While circRNAs can be translated, there have been few investigations into the biological functions of "translatable circRNAs" in the initiation and progression of gastric adenocarcinoma. In this study, we identified a circRNA, circMAP3K13, which inhibits the proliferation and migration of GC cells. CircMAP3K13 was found to encode a previously unreported 26 kDa protein, designated MAP3K13-232aa. Mechanistically, MAP3K13-232aa binds directly to the kinase domain of IKKα and enhances its activity, thereby promoting NF-κB signaling. This activation leads to upregulation of NLRP3 and increased cisplatin-induced pyroptosis in GC cells. Moreover, MAP3K13-232aa enhances pyroptosis and reduces tumorigenicity and metastasis in vivo. Taken together, both circMAP3K13 and its encoded protein MAP3K13-232aa represent potential therapeutic targets in GC.

摘要

胃癌(GC)是发展中国家最常见且致命的恶性肿瘤之一,在中国的发病率尤其高。环状RNA(circRNA)因其在疾病发病机制中的作用而受到越来越多的关注。虽然circRNA可以被翻译,但关于“可翻译circRNA”在胃腺癌发生和发展中的生物学功能的研究却很少。在本研究中,我们鉴定了一种环状RNA,即circMAP3K13,它可抑制GC细胞的增殖和迁移。发现circMAP3K13编码一种以前未报道的26 kDa蛋白,命名为MAP3K13-232aa。机制上,MAP3K13-232aa直接与IKKα的激酶结构域结合并增强其活性,从而促进NF-κB信号传导。这种激活导致NLRP3上调,并增加顺铂诱导的GC细胞焦亡。此外,MAP3K13-232aa在体内增强焦亡并降低致瘤性和转移能力。综上所述,circMAP3K13及其编码蛋白MAP3K13-232aa均代表GC潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b7/12402440/fd29850da1b1/41419_2025_7991_Fig1_HTML.jpg

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