LINC00921 reduces lung cancer radiosensitivity by destabilizing NUDT21 and driving aberrant MED23 alternative polyadenylation

• DOI: 10.1016/j.celrep.2023.113479
• Publication Date: 2023-11-24T04:06:28Z
• Authors: Nasha Zhang; Xijun Liu; Linying Huang; Jiajia Zeng; Chi Ma; Linyu Han; Wenwen Li; Jinming Yu; Ming Yang
• Keywords: Radiosensitivity; KLF2

Alternative polyadenylation (APA) plays a major role in controlling transcriptome diversity and therapeutic resistance of cancers. However, long non-coding RNAs (lncRNAs) involved pathological APA remain poorly defined. Here, we functionally characterize LINC00921, MED13L/P300-induced oncogenic lncRNA, show that it is required for global regulation non-small cell lung cancer (NSCLC). LINC00921 shows significant potential reducing NSCLC radiosensitivity, high levels are associated with poor prognosis patients treated radiotherapy. controls NUDT21 stability by facilitating binding the E3 ligase TRIP12. LINC00921-induced destabilization promotes 3′ UTR shortening MED23 mRNA via APA, which, turn, leads to elevated protein cells nuclear translocation β-catenin thereby activates expression multiple β-catenin/T factor (TCF)/lymphoid enhancer-binding (LEF)-regulated core oncogenes (c-Myc, CCND1, BMP4). These findings highlight importance annotating lncRNAs suggest clinical therapeutics advanced NSCLC.