1. LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells.
- Author
-
La, Ting, Chen, Song, Zhao, Xiao Hong, Zhou, Shuai, Xu, Ran, Teng, Liu, Zhang, Yuan Yuan, Ye, Kaihong, Xu, Liang, Guo, Tao, Jamaluddin, Muhammad Fairuz, Feng, Yu Chen, Tang, HaiJie, Wang, Yanliang, Xu, Qin, Gu, Yue, Cao, Huixia, Liu, Tao, Thorne, Rick F., and Shao, Feng-Min
- Subjects
- *
DNA repair , *LINCRNA , *CANCER cells , *P53 antioncogene , *DNA damage , *CARCINOGENESIS , *CELL cycle - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF