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High Expression of CARM1 Inhibits Lung Cancer Progression by Targeting TP53 by Regulating CTNNB1.

CARM1 高表达通过调控 ctnnb1 靶向 TP53 抑制肺癌进展。

  • 影响因子:1.92
  • DOI:10.1007/s00408-020-00324-7
  • 作者列表:"Hu B","Li X","Chen L","Liu Z
  • 发表时间:2020-04-01
Abstract

OBJECTIVE:To explore the role of CARM1 in lung cancer (LC) and its relationship with TP53 and CTNNB1. METHODS: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. RESULTS: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. CONCLUSION:Overexpression of CARM1 may inhibit the progression of LC by targeting TP53 via regulation CTNNB1.

摘要

目的: 探讨 CARM1 在肺癌 (LC) 中的作用及其与 TP53 、 ctnnb1 的关系。 方法: 将 H1299 和 PC14 细胞随机分为 ov-H1299 、 si-H1299 、 ov-PC14 、 si-PC14 、 Con-H1299 、 Con-PC14。分别采用 Transwell 实验、平板克隆形成实验和流式细胞术测定 6 组 LC 细胞的迁移、克隆形成能力和凋亡情况。Western blot 检测 6 组 CARM1 、 TP53 和 CTNNB1 的蛋白表达。应用 CHIP 法分析 JUN 和 TP53 启动子的联合特性。免疫共沉淀分析 TP53 与 CARM1/ctnnb1 的相互作用。采用 Cox 比例风险回归模型分析 CARM1 的表达与患者临床病理信息的相关性。使用 Kaplan-Meier 图确定 CARM1 与患者生存率之间的相关性。 结果: CARM1 高表达抑制了 LC 细胞的迁移和增殖,促进了 LC 细胞的凋亡。过表达 CARM1 促进 CARM1 和 TP53 的表达,而降低 CTNNB1 的表达。CARM1 补充 H1299 细胞诱导了 TP53 启动子上的 JUN 聚集。将 H1299 细胞中的 TP53 和 CARM1 蛋白/TP53 和 CTNNB1 蛋白免疫沉淀在一起。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。 结论: CARM1 过表达可能通过调控 ctnnb1 靶向 TP53 抑制 LC 的进展。

关键词: CARM1 CTNNB1 肺癌 TP53
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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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DOI:10.1016/j.annonc.2019.10.022
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