MED27 通过影响乳腺癌中的 Sp1 促进细胞的恶性行为。

MED27 promotes malignant behavior of cells by affecting Sp1 in breast cancer.

机构信息

Department of Oncology, The Central Hospital of Lishui City, Lishui, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6802-6808. doi: 10.26355/eurrev_202006_21669.

DOI:10.26355/eurrev_202006_21669

PMID:32633372

Abstract

OBJECTIVE

The aim of this study was to investigate the expression of mediator complex subunit 27 (MED27) in breast cancer (BC) and explore its effects on the proliferation and apoptosis of BC cells.

PATIENTS AND METHODS

The expression of MED27 in 60 BC tissues and para-cancer tissues was detected. Based on the significantly high expression level of MED27 in tumors, the tumor samples were divided into high-expression group and low-expression group according to the median standard, with 30 samples in each group. Then, the association between MED27 expression and clinicopathological features of patients was analyzed. The correlation between MED27 expression and survival time of patients was estimated using the Kaplan-Meier method. Next, the expression level of MED27 in cells was also measured using qRT-PCR assay. In vitro study, si-MED27 was designed to interfere with the expression of MED27 in MDA-MB-231 cells. To further explore the mechanism of MED27 in BC, the expression level of SP1 in cells was examined after different treatments.

RESULTS

In quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, MED27 was found to be highly expressed in both BC tissues and cells. Then, the relationship between MED27 expression and clinical pathological data was statistically analyzed, and it was found that MED27 expression was correlated with tumor size and grade. In the 60-month follow-up and Kaplan-Meier analysis, patients with high expression of MED27 had a poor prognosis. In in vitro study, MED27 expression in cells was down-regulated by transfection with si-MED27. Western blot (WB) analysis suggested that si-MED27 could effectively reduce the protein expression level of MED27 in cells, and the specificity protein 1 (Sp1) expression was also limited. In CCK-8, clone formation and flow cytometry experiments, the proliferation of cells with low MED27/Sp1 expression was suppressed, while cell apoptosis was promoted.

CONCLUSIONS

MED27 acted as an oncogene in BC. By affecting Sp1, MED27 could be a new therapeutic target for the treatment of BC.

摘要

目的

本研究旨在探讨中介复合物亚基 27（MED27）在乳腺癌（BC）中的表达，并探讨其对 BC 细胞增殖和凋亡的影响。

患者与方法

检测 60 例 BC 组织和癌旁组织中 MED27 的表达。根据肿瘤中 MED27 表达明显升高，将肿瘤标本按中位数标准分为高表达组和低表达组，每组 30 例。然后分析 MED27 表达与患者临床病理特征的关系。采用 Kaplan-Meier 法估计 MED27 表达与患者生存时间的相关性。接着，采用 qRT-PCR 检测细胞中 MED27 的表达水平。体外研究中，设计 si-MED27 干扰 MDA-MB-231 细胞中 MED27 的表达。为进一步探讨 MED27 在 BC 中的作用机制，检测了不同处理后细胞中 SP1 的表达水平。

结果

在定量逆转录-聚合酶链反应（qRT-PCR）检测中，发现 MED27 在 BC 组织和细胞中均高表达。然后，对 MED27 表达与临床病理数据的关系进行统计学分析，发现 MED27 表达与肿瘤大小和分级相关。在 60 个月的随访和 Kaplan-Meier 分析中，MED27 高表达的患者预后较差。在体外研究中，通过转染 si-MED27 下调细胞中 MED27 的表达。Western blot（WB）分析表明，si-MED27 可有效降低细胞中 MED27 的蛋白表达水平，同时限制特异性蛋白 1（Sp1）的表达。在 CCK-8、克隆形成和流式细胞术实验中，低 MED27/Sp1 表达的细胞增殖受到抑制，而细胞凋亡得到促进。