组蛋白甲基转移酶EHMT2对结直肠癌细胞生长的负调控CDKN1A

Kwangho Kim, Dae-Soo Kim, M. Son, Hyun-Soo Cho
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引用次数: 0

摘要

组蛋白甲基转移酶对癌基因和抑癌基因的表观遗传调控是结肠癌生长和转移的重要过程。尽管各种表观遗传修饰剂已被认为是结肠癌治疗的有吸引力的治疗靶点,但在结肠癌中减少副作用和提高治疗效果的替代表观遗传调控尚未得到彻底的探索。在这项研究中,我们通过rna测序确定了CDKN1A是EHMT2的直接靶点,并发现通过敲低EHMT2上调CDKN1A来增加生长抑制。此外,利用超低附着板的三维球体形成培养系统,我们证实了ehmt2相关的生长抑制和CDKN1A调控。因此,我们认为EHMT2可能是结肠癌治疗的一个治疗靶点,应该开发EHMT2抑制剂来有效治疗结肠癌。
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Negative regulation of CDKN1A by the histone methyltransferase EHMT2 for cell growth in colorectal cancer
The 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 the effectiveness of treatments has not been thoroughly explored. In this study, we identified CDKN1A as a direct target for EHMT2 by RNA-sequencing and found increased growth suppression via upregulation of CDKN1A by EHMT2 knockdown. In addition, using a 3-dimensional culture system for spheroid formation with an ultralow attachment plate, we confirmed EHMT2-related growth suppression and CDKN1A regulation. Thus, we suggest that EHMT2 may be a therapeutic target for colon cancer treatment, and an EHMT2 inhibitor should be developed for the effective treatment of colon cancer.
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