The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis
Teng Liu, Yuchen Feng, Su Guo, Pei Lin Wang, Teng Fei Qi, Yi Yue, Shi Xing Wang, Sheng Nan Zhang, Cai Xia Tang, Ting La, Yuan Yuan Zhang, Xiao Hong Zhao, Jin Nan Gao, Liyuan Wei, Didi Zhang, Jenny Wang, Yujie Shi, Xiaoying Liu, Jinming Li, Huixia Cao, Tao Liu, Rick F. Thorne, Lei Jin, Fengmin Shao, Xu Dong Zhang
Abstract
Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.