Negative regulation of CDKN1A by the histone methyltransferase EHMT2 for cell growth in colorectal cancer

Abstract

Background: Epigenetic regulation of oncogenes and tumor suppressor genes by histone methyltransferases is an important process for colon cancer growth and metastasis. Although various epigenetic modifiers have been recognized as attractive therapeutic targets for colon cancer treatment, alternative epigenetic regulation in colon cancer for reducing side effects and increasing effectiveness of treatments has not been thoroughly explored. Methods: To identify the overexpression of EHMT2 in colon cancer, we used the RNA-sequencing (RNA-seq) results (normal, n=41; tumor, n=286) derived from the The Cancer Genome Atlas (TCGA) portal. And we performed a 3-dimensional (3D) culture system for generating cell spheroids to assess the functions of EHMT2 in colon cancer, and using chromatin immunoprecipitation assays and RNA-seq results, we suggested EHMT2 direct target in colon cancer. Results: In this study, we identified CDKN1A as a direct target for EHMT2 by RNA-seq and found increased growth suppression via upregulation of CDKN1A by EHMT2 knockdown. In addition, using a 3D culture system for spheroid formation with a ULA plate, we confirmed EHMT2-related growth suppression and CDKN1A regulation. Conclusion: We suggest that EHMT2 is a therapeutic target for colon cancer treatment, and the development of an EHMT2 inhibitor is needed for the effective treatment of colon cancer.