Lamin B2 promotes the malignant phenotype of non-small cell lung cancer cells by upregulating dimethylation of histone 3 lysine 9
Lamin B2 promotes the malignant phenotype of non-small cell lung cancer cells by upregulating dimethylation of histone 3 lysine 9
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Lamin B2 通过上调组蛋白 3 赖氨酸 9 二甲基化促进非小细胞肺癌细胞的恶性表型
DOI：
10.1016/j.yexcr.2020.112090
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发表时间：
2020
影响因子：
3.7
通讯作者：
Wang En-Hua
中科院分区：
文献类型：
--
作者：
Zhang Mei-Yu;Han Yu-Chen;Han Qiang;Liang Yuan;Luo Yuan;Wei Lai;Yan Ting;Yang Yue;Liu Shu-Li;Wang En-Hua
核纤层蛋白B2与肿瘤增殖和迁移的关系尚不清楚。我们探索了核纤层蛋白B2对非小细胞肺癌（NSCLC）细胞的影响。采用组织芯片和免疫组化方法检测Lamin B2在NSCLC中的表达及其与临床病理因素的关系。蛋白质印迹法，免疫荧光分析，生物信息学研究核纤层蛋白B2对各种调控途径在癌症中的作用。进行细胞学实验以评估核纤层蛋白B2在肿瘤细胞中的表达。我们采用免疫共沉淀和染色质免疫共沉淀的方法来探讨核纤层蛋白B2与非小细胞肺癌之间关系的分子机制，并评估挽救实验的结果。Lamin B2在NSCLC中高表达，与淋巴结转移呈正相关。在NSCLC中，核纤层蛋白B2与细胞周期蛋白D1相互作用，上调G9α表达，从而增加H3 K9 me 2水平。H3 K9 me 2与E-cadherin基因（CDH 1）的启动子区结合，诱导CDH 1沉默并促进癌细胞迁移。因此，我们发现核纤层蛋白B2在NSCLC细胞中高度表达，并通过增加H3 K9 me 2水平促进其迁移，从而诱导E-cadherin基因沉默。
The relationship between Lamin B2 and tumor proliferation and migration is unclear. We explored the impact of Lamin B2 on non-small cell lung cancer (NSCLC) cells. Tissue microarray and immunohistochemistry were combined to evaluate Lamin B2 expression and its relationship with the clinicopathological factors found in NSCLC. Western blotting, immunofluorescence analysis, and bioinformatics were used to investigate the effects of Lamin B2 on various regulatory pathways in cancer. Cytological experiments were conducted to evaluate Lamin B2 expression in tumor cells. We conducted co-immunoprecipitation and chromatin immunoprecipitation to explore the molecular mechanisms underlying the relationship between Lamin B2 and NSCLC and evaluate the results of rescue experiments. Lamin B2 was highly expressed in NSCLC and positively correlated with lymph node metastasis. In NSCLC, Lamin B2 interacted with Cyclin D1, upregulating G9α expression, thus increasing H3K9me2 levels. H3K9me2 binds to the promoter region of the E-cadherin gene (CDH1) to induceCDH1silencing and promotes cancer cell migration. Thus, we found that Lamin B2 was highly expressed in NSCLC cells and promoted their migration by increasing H3K9me2 levels, which induced E-cadherin gene silencing.