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| DNMT3a在肺腺癌中的表达及癌细胞迁移的影响分析 |
| DNMT3a promotes the migration of lung adenocarcinoma cells by up-regulating Snail |
| 投稿时间：2024-03-12 |
| DOI：10.3969/j.issn.1000-0399.2024.08.002 |
| 中文关键词: 肺腺癌 甲基化转移酶3a 蜗牛家族转录因子 迁移 上皮间质转化 |
| 英文关键词: Lung adenocarcinoma DNA methyltransferase 3 alpha Snail Migration Epithelial-mesenchymal transition |
| 基金项目:安徽省重点研究与开发计划临床医学研究转化专项(编号:202304295107020047),安徽省儿童医院优秀专科医师培养计划(编号:eyrc034) |
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| 中文摘要: |
| 目的 探讨 DNA 甲基转移酶 3a（DNMT3a）在肺腺癌中的表达水平及影响肺腺癌细胞迁移的分子机制。方法 回顾性分析 2023 年 1~12 月在安徽医科大学第一附属医院胸外科接受手术治疗的 41 例肺腺癌患者临床资料，使用 IHC 和蛋白质印迹实验（WB）检测并分析 DNMT3a 在 41 例患者肺腺癌组织及癌旁组织中的表达水平；通过分析 TCGA 数据库揭示 DNMT3a 与肺腺癌患者预后关系。慢病毒介导 SK-LU-1 和 A549 细胞系过表达或敲低 DNMT3a，通过 IHC、WB、实时荧光定量聚合链反应（qRT-PCR）、DNMT3a抑制剂实验观察 DNMT3a 对蜗牛家族转录因子（Snail）表达的影响；细胞划痕实验和 Transwell 细胞迁移实验检测过表达或敲低DNMT3a 对肺腺癌细胞迁移的影响。结果 DNMT3a 高表达对比 DNMT3a 低表达的肺腺癌患者生存期较短，差异有统计学意义（P＜0.01）；DNMT3a 和 Snail 在肺腺癌组织中较癌旁组织相比均高表达（P＜0.01），且 DNMT3a 和 Snail 在肺腺癌组织中的表达呈正相关（r=0.612，P＜0.01）。与对照组相比，过表达 DNMT3a 的 SK-LU-1 细胞中 Snail 表达上调并增加了肺腺癌细胞的迁移数量（P＜0.01），敲低DNMT3a 的 A549 细胞中 Snail 表达下调并减少了肺腺癌细胞的迁移数量（P＜0.01）。结论 DNMT3a 在肺腺癌组织中高表达且与不良预后显著相关，DNMT3a 通过上调 Snail 的表达促进肺腺癌细胞的迁移。 |
| 英文摘要: |
| Objective The aim of the study was to investigate the expression of DNMT3a and the molecular mechanism of DNMT3a in lung adenocarcinoma. Methods The expression levels of DNMT3a in 41 pairs of lung adenocarcinoma tissues and adjacent tissues were detected and analyzed by IHC and Western blot in the First Affiliated Hospital of Anhui Medical University From January 2023 to December 2023. TCGA database was used to analyze the relationship between DNMT3a expression level and the prognosis of patients with lung adenocarcinoma. SK-LU-1 and A549 cells were transfected with lentivirus to over-express or knockdown DNMT3a expression, and the effect of DNMT3a on Snail expression were observed by IHC, Western blot, qRT-PCR, and DNMT3a inhibitor experiments. The effect of overexpression or knockdown of DNMT3a on the migration of lung adenocarcinoma cells was detected by Wound healing assay and Transwell cell migration assay. Results High expression of DNMT3a was significantly associated with poor prognosis of lung adenocarcinoma patients (P< 0.01). Compared with adjacent tissues, DNMT3a and Snail were both highly expressed in lung adenocarcinoma tissues (P<0.01), and the expression of DNMT3a and Snail was remarkably correlated in lung adenocarcinoma tissues through Mann-Kendall test(correlation coefficient=0.612, P<0.01). The prognosis of lung adenocarcinoma patients with high DNMT3a expression was poor (P<0.01). Compared with the control group, DNMT3a over-expression up-regulated the expression of Snail and promoted the migration in SK-LU-1 cells (P<0.01), while DNMT3a knockdown down-regulated the expression of Snail and inhibited the migration in A549 cells (P<0.01). Conclusion DNMT3a is highly expressed in human lung adenocarcinoma tissues and is significantly associated with poor prognosis. DNMT3a promotes the migration of lung adenocarcinoma cells through up-regulating the expression of Snail. |
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