A new IRES-mediated truncated Cx32 isoform inhibits global mRNA translation to suppress glioblastoma

• DOI: 10.1016/j.biopha.2023.114513
• Publication Date: 2023-03-15T23:26:53Z
• Authors: Shaoyi Cai; Fuhua Peng; Heng Tang; Liping Zhou; Zhiyou Chen; Penghan Wu; Yueling Ou; Liang Tao; Qin Wang
• Keywords: Brain Neoplasms; Cell Line, Tumor; Protein Biosynthesis; Humans; Protein Isoforms; RNA, Messenger; Internal Ribosome Entry Sites; Glioblastoma; Gap Junction beta-1 Protein; 3. Good health

Glioblastoma (GBM) is the most lethal malignant primary brain tumor. Although multimodal therapy has been applied for GBM, median survival time remains less than 16 months. Thus, better therapeutic targets in GBM are urgently needed. Herein, we first identified five new N-terminal-truncated Cx32 isoforms (GJB1-28k, GJB1-22k, GJB1-20k, GJB1-15k, and GJB1-13k) further demonstrated that they were generated via cap-independent internal translation through ribosome entry sites (IRESs) coding sequence of GJB1 mRNA. Among these isoforms, GJB1-13k inhibited proliferation, promoted apoptosis, limited cell cycle progression cells by inhibiting global mRNA translation. In vivo experiments confirmed antitumor activity against cells. addition, TSR3, a ribosomal maturation factor, was to directly interact with GJB1-13k. Moreover, high TSR3 expression exhibited low sensitivity treatment, while restored knockdown. Our work identifies IRES-mediated protein, GJB1-13k, suggests overexpression or combined targeting constitutes potential strategy GBM.