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Int J Med Sci 2023; 20(7):901-917. doi:10.7150/ijms.80073 This issue Cite

Research Paper

DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation

Wei-Chao Su1*, Xiao-Mei Mao2*, Si-Yang Li3*, Chun-Ying Luo4,5*, Rui Fan3, Hai-Feng Jiang1, Lin-Jun Zhang3, Ya-Tao Wang1, Guo-Qiang Su1,5✉, Dong-Yan Shen3✉

1. Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, Fujian Province, P.R. China.
2. School of Pharmaceutical Science and Technology, Suzhou Chien-Shiung Institute of Technology, Suzhou 215411, Jiangsu Province, P.R. China.
3. Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, Fujian Province, P.R. China.
4. Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Province, P.R. China.
5. Medical College, Guangxi University, Nanning 530004, Guangxi Province, P.R. China.
* These authors contributed equally to this work.

✉ Corresponding authors: Dong-Yan Shen3, No. 55 Zhenhai Road, Xiamen 361003, PR China. Email address: shendongyanedu.cn. Guo-Qiang Su1, No. 55 Zhenhai Road, Xiamen 361003, PR China. E-mail address: suguoqiangedu.cn

Citation:
Su WC, Mao XM, Li SY, Luo CY, Fan R, Jiang HF, Zhang LJ, Wang YT, Su GQ, Shen DY. DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation. Int J Med Sci 2023; 20(7):901-917. doi:10.7150/ijms.80073. https://www.medsci.org/v20p0901.htm
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Abstract

Graphic abstract

DPY30, a core subunit of the SET1/MLL histone H3K4 methyltransferase complexes, plays an important role in diverse biological functions through the epigenetic regulation of gene transcription, especially in cancer development. However, its involvement in human colorectal carcinoma (CRC) has not been elucidated yet. Here we demonstrated that DPY30 was overexpressed in CRC tissues, and significantly associated with pathological grading, tumor size, TNM stage, and tumor location. Furthermore, DPY30 knockdown remarkably suppressed the CRC cell proliferation through downregulation of PCNA and Ki67 in vitro and in vivo, simultaneously induced cell cycle arrest at S phase by downregulating Cyclin A2. In the mechanistic study, RNA-Seq analysis revealed that enriched gene ontology of cell proliferation and cell growth was significantly affected. And ChIP result indicated that DPY30 knockdown inhibited H3 lysine 4 trimethylation (H3K4me3) and attenuated interactions between H3K4me3 with PCNA, Ki67 and cyclin A2 respectively, which led to the decrease of H3K4me3 establishment on their promoter regions. Taken together, our results demonstrate overexpression of DPY30 promotes CRC cell proliferation and cell cycle progression by facilitating the transcription of PCNA, Ki67 and cyclin A2 via mediating H3K4me3. It suggests that DPY30 may serve as a potential therapeutic molecular target for CRC.

Keywords: DPY30, Colorectal carcinoma, Cell proliferation, Cell cycle, H3K4 trimethylation

Citation styles

APA
Su, W.C., Mao, X.M., Li, S.Y., Luo, C.Y., Fan, R., Jiang, H.F., Zhang, L.J., Wang, Y.T., Su, G.Q., Shen, D.Y. (2023). DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation. International Journal of Medical Sciences, 20(7), 901-917. https://doi.org/10.7150/ijms.80073.

ACS
Su, W.C.; Mao, X.M.; Li, S.Y.; Luo, C.Y.; Fan, R.; Jiang, H.F.; Zhang, L.J.; Wang, Y.T.; Su, G.Q.; Shen, D.Y. DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation. Int. J. Med. Sci. 2023, 20 (7), 901-917. DOI: 10.7150/ijms.80073.

NLM
Su WC, Mao XM, Li SY, Luo CY, Fan R, Jiang HF, Zhang LJ, Wang YT, Su GQ, Shen DY. DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation. Int J Med Sci 2023; 20(7):901-917. doi:10.7150/ijms.80073. https://www.medsci.org/v20p0901.htm

CSE
Su WC, Mao XM, Li SY, Luo CY, Fan R, Jiang HF, Zhang LJ, Wang YT, Su GQ, Shen DY. 2023. DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation. Int J Med Sci. 20(7):901-917.

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