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
Affiliations
- Liu Teng
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Yu Chen Feng
- School of Medicine and Public Health, The University of Newcastle
- Su Tang Guo
- Department of Molecular Biology, Shanxi Cancer Hospital and Institute
- Pei Lin Wang
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Teng Fei Qi
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Yi Meng Yue
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Shi Xing Wang
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Sheng Nan Zhang
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Cai Xia Tang
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Ting La
- School of Biomedical Sciences and Pharmacy, The University of Newcastle
- Yuan Yuan Zhang
- School of Biomedical Sciences and Pharmacy, The University of Newcastle
- Xiao Hong Zhao
- School of Biomedical Sciences and Pharmacy, The University of Newcastle
- Jin Nan Gao
- Department of Breast Surgery, Shanxi Bethune Hospital
- Li Yuan Wei
- Department of Breast Surgery, Shanxi Bethune Hospital
- Didi Zhang
- Orthopaedics Department, John Hunter Hospital, Hunter New England Health
- Jenny Y. Wang
- Children’s Cancer Institute Australia for Medical Research, University of New South Wales
- Yujie Shi
- Department of Pathology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital
- Xiao Ying Liu
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Jin Ming Li
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Huixia Cao
- Department of Nephrology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital
- Tao Liu
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Rick F. Thorne
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Lei Jin
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- Feng-Min Shao
- Department of Nephrology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital
- Xu Dong Zhang
- Translational Research Institute, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University
- DOI
- https://doi.org/10.1038/s41467-021-24099-4
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 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.
