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

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

  • Cell Death Dis. 2025 Sep 1;16(1):667. doi: 10.1038/s41419-025-07991-5.
Kaining Du # 1 2,  Xiaojing Zhang # 1 2 3,  Ying Qin # 4,  Huizhen Ma 1,  Chuhan Bing 1,  Shiqi Deng 1 2,  Yang Chen 1 2,  Jiequan Qin 1,  Shanshan Chang 1 2,  Siyu Xiao 1,  Lehua Peng 1,  Xiaoya Xie 1,  Xianling Feng 1,  Xianli Fu 5,  Yanjie Wei 6,  Xinmin Fan 1,  Hassan Ashktorab 7,  Duane Smoot 8,  Zhe Jin 1 2,  Yin Peng 9 10
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China.
  • 2 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, PR China.
  • 3 Department of Pathology, Guangdong Province Key Laboratory of Molecular Oncologic Pathology, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, PR China.
  • 4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, PR China.
  • 5 Department of Pathology, Shenzhen University General Hospital, Shenzhen, Guangdong, PR China.
  • 6 Center for High Performance Computing, Shenzhen Institutes of Advanced Technology, Shenzhen, Guangdong, PR China.
  • 7 Department of Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, USA.
  • 8 Department of Medicine, Meharry Medical Center, Nashville, TN, USA.
  • 9 Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China. ypeng@szu.edu.cn.
  • 10 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, PR China. ypeng@szu.edu.cn.
  • # Contributed equally.
PMID: 40890114 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.

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