MAP3K13-232aa encoded by circMAP3K13 enhances cisplatin-induced pyroptosis by directly binding to IKKα in gastric adenocarcinoma
Kaining Du, Xiaojing Zhang, Ying� Qin, Huizhen Ma, Chuhan Bing, Shiqi Deng, Yang Chen, Jiequan Qin, Shanshan Chang, Siyu Xiao, Lehua Peng, Xiaoya Xie, Xianling Feng, Xianli Fu, Yanjie Wei, Xinmin Fan, Hassan Ashktorab, Duane T. Smoot, Zhe Jin, Yin Peng
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.