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 () and Xu Dong Zhang ()
Additional contact information
Liu Teng: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Yu Chen Feng: The University of Newcastle
Su Tang Guo: Shanxi Cancer Hospital and Institute
Pei Lin Wang: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Teng Fei Qi: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Yi Meng Yue: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Shi Xing Wang: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Sheng Nan Zhang: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Cai Xia Tang: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Ting La: The University of Newcastle
Yuan Yuan Zhang: The University of Newcastle
Xiao Hong Zhao: The University of Newcastle
Jin Nan Gao: Shanxi Bethune Hospital
Li Yuan Wei: Shanxi Bethune Hospital
Didi Zhang: John Hunter Hospital, Hunter New England Health
Jenny Y. Wang: University of New South Wales
Yujie Shi: Zhengzhou University People’s Hospital
Xiao Ying Liu: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Jin Ming Li: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Huixia Cao: Zhengzhou University People’s Hospital
Tao Liu: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Rick F. Thorne: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Lei Jin: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
Feng-Min Shao: Zhengzhou University People’s Hospital
Xu Dong Zhang: Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24099-4

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