Shuang Wu, Xiangyu Dai, Yang Xia, Qingsong Zhao, Heng Zhao, Zhimin Shi, Xin Yin, Xue Liu, Aijie Zhang, Zhihui Yao, Hao Zhang, Qun Li, Rick Francis Thorne, Shangxin Zhang, Weiwei Sheng, Wanglai Hu, Hao Gu
The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T cell recruitment. circDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging the IGF2BP3 half-life, which in turn sustains mRNA levels of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators...
April 12, 2024: Cell Reports