The Long Noncoding RNA LUCAT1 Promotes Cell Proliferation via Binding with NCL and Regulating MYC Expression in Colorectal Cancer

Background: Long noncoding RNA (LncRNA) LUCAT1 was recently reported to be upregulated and play an important role in multiple types of cancer, especially colorectal cancer (CRC). However, the detailed molecular mechanisms of LUCAT1 in CRC remain incompletely understood. The aim of this study was to investigate the transcriptional regulation role and interacting partners of LUCAT1 in CRC.Methods: A systematic and comprehensive analysis of LUACT1 expression was performed in the TCGA databases and in 36 CRC samples. Proliferation capacity was investigated through knockout of LUCAT1 in vitro and in vivo. In addition, its protein binding partner was identified and validated using CHIRP-MS and RNA immunoprecipitation assays. Their key interaction sites on LUCAT1 were predicted by bioinformatics analysis and verified by luciferase reporter assay and a series of mutant constructs. Furthermore, the downstream targets of LUCAT1 were confirmed via CHIP and luciferase reporter assays.Results: LUCAT1 was significantly up-regulated in CRC samples and associated with poor prognosis, promoting proliferation in vitro and in vivo. LUCAT1 could regulate MYC expression and directly bind to NCL via putative G-quadruplex-forming regions from nucleotides 717 to 746 of LUCAT1. Moreover, NCL could directly bind to MYC NHE III1 region and negative regulate MYC gene expression in CRC. Furthermore, we confirmed that silencing NCL could restore the LUCAT1-KO-mediated inhibition in MYC expression and proliferation of CRC cells.Conclusion: LUCAT1 plays important roles in CRC proliferation by interacting with NCL and may serve as a prognostic biomarker and effective therapeutic target for CRC.Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81602568, No. 81773130, No. 81702336), China Postdoctoral Science Foundation (No. 2018M643009) and The New Xiangya Talent Projects of the Third Xiangya Hospital of Central South University (No. JY201611).Declaration of Interests: The authors declare that they have no conflict of interest.Ethical Approval Statement: The study was approved by the ethics committee of the Third XiangYa Hospital of Central South University