Nature Communications (Jun 2021)

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis

  • Liu Teng,
  • Yu Chen Feng,
  • Su Tang Guo,
  • Pei Lin Wang,
  • Teng Fei Qi,
  • Yi Meng Yue,
  • Shi Xing Wang,
  • Sheng Nan Zhang,
  • Cai Xia Tang,
  • Ting La,
  • Yuan Yuan Zhang,
  • Xiao Hong Zhao,
  • Jin Nan Gao,
  • Li Yuan Wei,
  • Didi Zhang,
  • Jenny Y. Wang,
  • Yujie Shi,
  • Xiao Ying Liu,
  • Jin Ming Li,
  • Huixia Cao,
  • Tao Liu,
  • Rick F. Thorne,
  • Lei Jin,
  • Feng-Min Shao,
  • Xu Dong Zhang

DOI
https://doi.org/10.1038/s41467-021-24099-4
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 17

Abstract

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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.