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EZH2 通过 E2F1、GLI1、CDK3 和 Mcm4 调控胰腺癌细胞。

EZH2 regulates pancreatic cancer cells through E2F1, GLI1, CDK3, and Mcm4.

机构信息

Department of Clinical Laboratory, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300120, China.

Department of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No. 354 Beima Road, Hongqiao District, Tianjin, 300120, China.

出版信息

Hereditas. 2023 May 17;160(1):23. doi: 10.1186/s41065-023-00280-1.

Abstract

Pancreatic cancer (PC) is one of the most common malignant tumors in digestive tract. To explore the role of epigenetic factor EZH2 in the malignant proliferation of PC, so as to provide effective medical help in PC. Sixty paraffin sections of PC were collected and the expression of EZH2 in PC tissues was detected by immunohistochemical assay. Three normal pancreas tissue samples were used as controls. The regulation of EZH2 gene on proliferation and migration of normal pancreatic cell and PC cell were determined by MTS, colony forming, Ki-67 antibody, scratch and Transwell assays. Through differential gene annotation and differential gene signaling pathway analysis, differentially expressed genes related to cell proliferation were selected and verified by RT-qPCR. EZH2 is mainly expressed in the nuclei of pancreatic tumor cells, but not in normal pancreatic cells. The results of cell function experiments showed that EZH2 overexpression could enhance the proliferation and migration ability of PC cell BXPC-3. Cell proliferation ability increased by 38% compared to the control group. EZH2 knockdown resulted in reduced proliferation and migration ability of cells. Compared with control, proliferation ability of cells reduced by 16%-40%. The results of bioinformatics analysis of transcriptome data and RT-qPCR demonstrated that EZH2 could regulate the expression of E2F1, GLI1, CDK3 and Mcm4 in normal and PC cells. The results revealed that EZH2 might regulate the proliferation of normal pancreatic cell and PC cell through E2F1, GLI1, CDK3 and Mcm4.

摘要

胰腺癌(PC)是消化道最常见的恶性肿瘤之一。为了探讨表观遗传因子 EZH2 在 PC 恶性增殖中的作用,为 PC 提供有效的医学帮助。收集了 60 例 PC 石蜡切片,通过免疫组织化学法检测 PC 组织中 EZH2 的表达。以 3 例正常胰腺组织作为对照。通过 MTS、集落形成、Ki-67 抗体、划痕和 Transwell 检测,确定 EZH2 基因对正常胰腺细胞和 PC 细胞增殖和迁移的调控作用。通过差异基因注释和差异基因信号通路分析,选择与细胞增殖相关的差异表达基因,并通过 RT-qPCR 进行验证。EZH2 主要在胰腺肿瘤细胞的核内表达,而不在正常胰腺细胞内表达。细胞功能实验结果表明,EZH2 过表达可增强 PC 细胞 BXPC-3 的增殖和迁移能力。与对照组相比,细胞增殖能力增加了 38%。EZH2 敲低导致细胞增殖和迁移能力降低。与对照组相比,细胞增殖能力降低了 16%-40%。转录组数据和 RT-qPCR 的生物信息学分析结果表明,EZH2 可调节正常和 PC 细胞中 E2F1、GLI1、CDK3 和 Mcm4 的表达。结果表明,EZH2 可能通过 E2F1、GLI1、CDK3 和 Mcm4 调节正常胰腺细胞和 PC 细胞的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbdb/10190069/e8cd864d5a76/41065_2023_280_Fig1_HTML.jpg

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