Department of Medical Oncology, Shanghai Minhang TCM Hospital (Shanghai Minhang Hospital of Traditional Chinese Medicine), No. 3071 HeChuan Road, Minhang District, Shanghai, 201103, China.
Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 725 Wanping South Road, Xuhui District, Shanghai, 200032, China.
Lung. 2020 Apr;198(2):415-422. doi: 10.1007/s00408-020-00324-7. Epub 2020 Feb 7.
To explore the role of CARM1 in lung cancer (LC) and its relationship with TP53 and CTNNB1.
Lung cells H1299 and PC14 were randomly divided into six groups: ov-H1299, si-H1299, ov-PC14, si-PC14, Con-H1299, and Con-PC14. Transwell assay, plate clone formation assay, and flow cytometry were used to determine the migration, clone formation capacity, and apoptosis situation of LC cells in the six groups, respectively. Western blot assay was used to determine the protein expression of CARM1, TP53, and CTNNB1 in the six groups. CHIP assay was applied to analyze the combined characteristics of JUN and TP53 promoter. Co-immunoprecipitation was used to analyze the interaction between TP53 and CARM1/CTNNB1. Cox proportional hazard regression model was used to analyze the relevance between the expression of CARM1 and clinicopathological information of the patient. Kaplan-Meier plot was used to determine the relevance between CARM1 and patient survival.
High expression of CARM1 inhibits the migration and proliferation of LC cells and promoted the apoptosis of LC cell. Overexpression of CARM1 promotes the expression of CARM1 and TP53, while decreases CTNNB1 expression. CARM1 supplementation of H1299 cells induced JUN aggregation on the TP53 promoter. TP53 and CARM1 protein/TP53 and CTNNB1 protein in H1299 cells were immunoprecipitated together. High expression of CARM1was negatively correlated with the degree of tumor metastasis. The survival period of patients with high expression CARM1 was greater than that of low expression.
Overexpression of CARM1 may inhibit the progression of LC by targeting TP53 via regulation CTNNB1.
探讨 CARM1 在肺癌（LC）中的作用及其与 TP53 和 CTNNB1 的关系。
随机将 H1299 肺细胞和 PC14 细胞分为六组：ov-H1299 组、si-H1299 组、ov-PC14 组、si-PC14 组、Con-H1299 组和 Con-PC14 组。Transwell 检测、平板克隆形成实验和流式细胞术分别检测六组 LC 细胞的迁移、克隆形成能力和凋亡情况。Western blot 检测六组细胞中 CARM1、TP53 和 CTNNB1 的蛋白表达。CHIP 检测 JUN 和 TP53 启动子结合特征。免疫共沉淀分析 TP53 与 CARM1/CTNNB1 的相互作用。Cox 比例风险回归模型分析 CARM1 表达与患者临床病理信息的相关性。Kaplan-Meier 图分析 CARM1 与患者生存的相关性。
CARM1 高表达抑制 LC 细胞的迁移和增殖，促进 LC 细胞凋亡。CARM1 过表达促进 CARM1 和 TP53 的表达，同时降低 CTNNB1 的表达。H1299 细胞中 CARM1 的补充诱导 JUN 在 TP53 启动子上聚集。H1299 细胞中 TP53 蛋白/CARM1 和 TP53 蛋白/CTNNB1 蛋白共免疫沉淀。CARM1 高表达与肿瘤转移程度呈负相关。CARM1 高表达患者的生存期大于低表达患者。
通过调节 CTNNB1，CARM1 过表达可能通过靶向 TP53 抑制 LC 的进展。
