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- Title
The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.
- Authors
Teng, Liu; Feng, Yu Chen; Guo, Su Tang; Wang, Pei Lin; Qi, Teng Fei; Yue, Yi Meng; Wang, Shi Xing; Zhang, Sheng Nan; Tang, Cai Xia; La, Ting; Zhang, Yuan Yuan; Zhao, Xiao Hong; Gao, Jin Nan; Wei, Li Yuan; Zhang, Didi; Wang, Jenny Y.; Shi, Yujie; Liu, Xiao Ying; Li, Jin Ming; Cao, Huixia
- 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. Genomic amplification of chromosome 3q often encodes proteins that contribute to cancer development. Here the authors identify a non-coding product of the 3q region, the lncRNA PLANE that promotes tumorigenesis through the deregulation of transcriptional corepressor NCOR2 pre-mRNA splicing.
- Subjects
CARCINOGENESIS; LINCRNA; ONCOGENIC proteins; CANCER cell proliferation; NUCLEOPROTEINS
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-24099-4