Advanced Science (Mar 2023)
LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53‐Defective Cancer Cells
- Ting La,
- Song Chen,
- Xiao Hong Zhao,
- Shuai Zhou,
- Ran Xu,
- Liu Teng,
- Yuan Yuan Zhang,
- Kaihong Ye,
- Liang Xu,
- Tao Guo,
- Muhammad Fairuz Jamaluddin,
- Yu Chen Feng,
- Hai Jie Tang,
- Yanliang Wang,
- Qin Xu,
- Yue Gu,
- Huixia Cao,
- Tao Liu,
- Rick F. Thorne,
- Feng‐Min Shao,
- Xu Dong Zhang,
- Lei Jin
Affiliations
- Ting La
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Song Chen
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Xiao Hong Zhao
- Noncoding Cancer Biomarkers and Therapeutics Group Cancer Detection & Therapy Research Program Hunter Medical Research Institute CallaghanNew South Wales 2305 Australia
- Shuai Zhou
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Ran Xu
- Noncoding Cancer Biomarkers and Therapeutics Group Cancer Detection & Therapy Research Program Hunter Medical Research Institute CallaghanNew South Wales 2305 Australia
- Liu Teng
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Yuan Yuan Zhang
- Noncoding Cancer Biomarkers and Therapeutics Group Cancer Detection & Therapy Research Program Hunter Medical Research Institute CallaghanNew South Wales 2305 Australia
- Kaihong Ye
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Liang Xu
- Noncoding Cancer Biomarkers and Therapeutics Group Cancer Detection & Therapy Research Program Hunter Medical Research Institute CallaghanNew South Wales 2305 Australia
- Tao Guo
- Institute of Future Agriculture Northwest A&F University Yangling Shaanxi 712100 China
- Muhammad Fairuz Jamaluddin
- School of Biomedical Sciences and Pharmacy The University of Newcastle CallaghanNew South Wales 2308 Australia
- Yu Chen Feng
- Noncoding Cancer Biomarkers and Therapeutics Group Cancer Detection & Therapy Research Program Hunter Medical Research Institute CallaghanNew South Wales 2305 Australia
- Hai Jie Tang
- Noncoding Cancer Biomarkers and Therapeutics Group Cancer Detection & Therapy Research Program Hunter Medical Research Institute CallaghanNew South Wales 2305 Australia
- Yanliang Wang
- Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and Immunology Henan Provincial Clinical Research Center for Kidney Disease Henan Provincial People's Hospital ZhengzhouHenan 450053 China
- Qin Xu
- Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and Immunology Henan Provincial Clinical Research Center for Kidney Disease Henan Provincial People's Hospital ZhengzhouHenan 450053 China
- Yue Gu
- Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and Immunology Henan Provincial Clinical Research Center for Kidney Disease Henan Provincial People's Hospital ZhengzhouHenan 450053 China
- Huixia Cao
- Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and Immunology Henan Provincial Clinical Research Center for Kidney Disease Henan Provincial People's Hospital ZhengzhouHenan 450053 China
- Tao Liu
- Children's Cancer Institute Australia for Medical Research University of New South Wales SydneyNew South Wales 2750 Australia
- Rick F. Thorne
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Feng‐Min Shao
- Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and Immunology Henan Provincial Clinical Research Center for Kidney Disease Henan Provincial People's Hospital ZhengzhouHenan 450053 China
- Xu Dong Zhang
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- Lei Jin
- Translational Research Institute Henan Provincial and Zhengzhou City Key laboratory of Non‐coding RNA and Cancer Metabolism Henan International Join Laboratory of Non‐coding RNA and Metabolism in Cancer Henan Provincial People's Hospital Academy of Medical Sciences Zhengzhou University ZhengzhouHenan 450053 China
- DOI
- https://doi.org/10.1002/advs.202204599
- Journal volume & issue
-
Vol. 10,
no. 7
pp. n/a – n/a
Abstract
Abstract P53 inactivation occurs in about 50% of human cancers, where p53‐driven p21 activity is devoid and p27 becomes essential for the establishment of the G1/S checkpoint upon DNA damage. Here, this work shows that the E2F1‐responsive lncRNA LIMp27 selectively represses p27 expression and contributes to proliferation, tumorigenicity, and treatment resistance in p53‐defective colon adenocarcinoma (COAD) cells. LIMp27 competes with p27 mRNA for binding to cytoplasmically localized hnRNA0, which otherwise stabilizes p27 mRNA leading to cell cycle arrest at the G0/G1 phase. In response to DNA damage, LIMp27 is upregulated in both wild‐type and p53‐mutant COAD cells, whereas cytoplasmic hnRNPA0 is only increased in p53‐mutant COAD cells due to translocation from the nucleus. Moreover, high LIMp27 expression is associated with poor survival of p53‐mutant but not wild‐type p53 COAD patients. These results uncover an lncRNA mechanism that promotes p53‐defective cancer pathogenesis and suggest that LIMp27 may constitute a target for the treatment of such cancers.
Keywords
