MAP3K13-232aa encoded by circMAP3K13 enhances cisplatin-induced pyroptosis by directly binding to IKKα in gastric adenocarcinoma
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.
Authors
- Shiqi Deng (ORCID: https://orcid.org/0000-0002-2128-1521)
- Shanshan Chang (ORCID: https://orcid.org/0009-0003-6566-0800)
- Zhe Jin (ORCID: https://orcid.org/0000-0002-4717-1558)
- Yanjie Wei (ORCID: https://orcid.org/0000-0002-4791-7540)
- Xianli Fu
- Huizhen Ma (ORCID: https://orcid.org/0009-0007-5840-9844)
- Duane T. Smoot
- Jiequan Qin
- Kaining Du
- Yang Chen (ORCID: https://orcid.org/0000-0002-2502-4960)
- Hassan Ashktorab (ORCID: https://orcid.org/0000-0002-4048-4666)
- Xiaojing Zhang (ORCID: https://orcid.org/0000-0002-0595-3500)
- Bing Chen (ORCID: https://orcid.org/0000-0001-8102-7333)
- Xianling Feng (ORCID: https://orcid.org/0000-0002-9097-3345)
- Xiaoya Xie
- Siyu Xiao (ORCID: https://orcid.org/0000-0001-7038-9531)
- Ying� Qin (ORCID: https://orcid.org/0000-0003-4365-586X)
- Yin Peng (ORCID: https://orcid.org/0000-0001-7524-7508)
- Xinmin Fan
- Lehua Peng
Institutions
- Meharry Medical College (US)
- Howard University (US)
- Shenzhen University (CN)
- University of Hong Kong - Shenzhen Hospital (CN)
- Shenzhen University Health Science Center (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Shenzhen Second People's Hospital (CN)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1038/s41419-025-07991-5
- Citations
- 4
- Primary Topic
- Circular RNAs in diseases
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Natural Science Foundation of China
- Shenzhen University