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, we show 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 a lncRNA mechanism that promotes p53-defective cancer pathogenesis and suggest that LIMp27 may constitute a target for the treatment of such cancers.
[doi:10.25345/C5SN01844]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: lncRNA ; LIMp27 ; p27 ; hnRNPA0 ; E2F1 ; Colon cancer
Principal Investigators: (in alphabetical order) |
Lei Jin, The University of Newcastle, Australia Muhammad Fairuz Jamaluddin, University of Newcastle, Australia Ting La, The University of Newcastle, Australia Xu Dong Zhang, The University of Newcastle, Australia |
Submitting User: | MFJ003 |
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