LIG1 Promotes the Development of Colorectal Cancer by Regulating UHRF1 to Promote MEG3 Methylation Level

Abstract

Background: DNA ligase 1 (LIG1) can regulate ubiquitin like with PHD and ring finger domains 1 (UHRF1) to the replication site, thereby maintaining DNA methylation, a biological behavior associated with the occurrence of colorectal cancer (CRC). On this basis, this study is engineered to explore whether LIG1 could affect the development of CRC by regulating UHRF1 to promote maternally expressed 3 (MEG3) methylation. Methods: The expressions of LIG1, UHRF1, and MEG3 in CRC were analyzed using bioinformatics and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Co-Immunoprecipitation (Co-IP), Western blot, and Chromatin Immunoprecipitation (ChIP) were used to determine the interaction between UHRF1 and MEG3. Methylation of the MEG3 promoter was determined by Quantitative Methylation-Specific PCR (qMSP). The effects of LIG1 and UHRF1 on CRC cell viability, migration, invasion, and epithelial-mesenchymal transformation (EMT) were studied by loss- and gain-of-function and rescue experiments. Results: LIG1 and UHRF1 levels were up-regulated while MEG3 level was down-regulated in CRC. Overexpression of LIG1 or UHRF1 promoted the migration, invasion, and EMT of CRC cells, while shLIG1 or shUHRF1 had the opposite effect. LIG1 regulated UHRF1 to suppress MEG3 expression and promote MEG3 methylation. There existed negative interactions between shUHRF1 and overexpression of LIG1 and between shLIG1 and overexpression of UHRF1 in the regulation of CRC cells. Conclusion: LIG1 promotes CRC development by regulating UHRF1 to increase MEG3 methylation.