- Title
- LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells
- Creator
- La, Ting; Chen, Song; Jamaluddin, Muhammad Fairuz; Feng, Yu Chen; Tang, Hai Jie; Wang, Yanliang; Xu, Qin; Gu, Yue; Cao, Huixia; Liu, Tao; Thorne, Rick F.; Shao, Feng-Min; Zhao, Xiao Hong; Zhang, Xu Dong; Jin, Lei; Zhou, Shuai; Xu, Ran; Teng, Liu; Zhang, Yuan Yuan; Ye, Kaihong; Xu, Liang; Guo, Tao
- Relation
- Advanced Science Vol. 10, Issue 7, no. 2204599
- Publisher Link
- http://dx.doi.org/10.1002/advs.202204599
- Publisher
- Wiley-VCH Verlag GmbH & Co. KGaA
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- colon cancer; E2F1; hnRNPA0; lncRNA; LIMp27; p27; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1479105
- Identifier
- uon:50273
- Identifier
- ISSN:2198-3844
- Language
- eng
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