LCAT1 is an oncogenic LncRNA by stabilizing the IGF2BP2-CDC6 axis. Cell Death Dis 2022 Oct 18;13(10):877
Date
10/19/2022Pubmed ID
36257938Pubmed Central ID
PMC9579176DOI
10.1038/s41419-022-05316-4Scopus ID
2-s2.0-85140077170 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Long non-coding RNAs (lncRNAs) is known to play vital roles in modulating tumorigenesis. We previously reported that LCAT1, a novel lncRNA, promotes the growth and metastasis of lung cancer cells both in vitro and in vivo. However, the underlying mechanism(s) of LCAT1 as an oncogenic regulator remains elusive. Here, we showed that LCAT1 physically interacts with and stabilizes IGF2BP2, an m6A reader protein, by preventing its degradation via autolysosomes. IGF2BP2 is overexpressed in lung cancer tissues, which is associated with poor survival of non-small cell lung cancer patients, suggesting its oncogenic role. Biologically, IGF2BP2 depletion inhibits growth and survival as well as the migration of lung cancer cells. Mechanistically, the LCAT1/IGF2BP2 complex increased the levels of CDC6, a key cell cycle regulator, by stabilizing its mRNA in an m6A-dependent manner. Like IGF2BP2, CDC6 is also overexpressed in lung cancer tissues with poor patient survival, and CDC6 knockdown has oncogenic inhibitory activity. Taken together, the LCAT1-IGF2BP2-CDC6 axis appears to play a vital role in promoting the growth and migration of lung cancer cells, and is a potential therapeutic target for lung cancer. Importantly, our finding also highlights a previously unknown critical role of LCAT1 in m6A-dependent gene regulation by preventing autolytic degradation of IGF2BP2.
Author List
Yang J, Qian X, Qiu Q, Xu L, Pan M, Li J, Ren J, Lu B, Qiu T, Chen E, Ying K, Zhang H, Lu Y, Liu PMESH terms used to index this publication - Major topics in bold
CarcinogenesisCarcinoma, Non-Small-Cell Lung
Cell Cycle Proteins
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
MicroRNAs
Nuclear Proteins
RNA, Long Noncoding
RNA, Messenger
RNA-Binding Proteins