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新型预后标志物EHMT2通过调控HSPD1参与乳腺癌细胞增殖。

The novel prognostic marker, EHMT2, is involved in cell proliferation via HSPD1 regulation in breast cancer.

作者信息

Kim Seon-Kyu, Kim Kwangho, Ryu Jea-Woon, Ryu Tae-Young, Lim Jung Hwa, Oh Jung-Hwa, Min Jeong-Ki, Jung Cho-Rok, Hamamoto Ryuji, Son Mi-Young, Kim Dae-Soo, Cho Hyun-Soo

机构信息

Korea Research Institute of Bioscience and Biotechnology, Daejeon 305‑333, Republic of Korea.

Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea.

出版信息

Int J Oncol. 2019 Jan;54(1):65-76. doi: 10.3892/ijo.2018.4608. Epub 2018 Oct 26.

Abstract

Molecular classifications of breast cancer (BRC), such as human epidermal growth factor receptor 2 (HER2), luminal A and luminal B, have been developed to reduce unnecessary treatment by dividing patients with BRC into low‑ and high‑risk progression groups. However, these methods do not cover all of the pathological characteristics of BRC, and investigations into novel prognostic/therapeutic markers are thus continually required. In this study, we identified the overexpression of the histone methyltransferase, euchromatic histone‑lysine N‑methyltransferase 2 (EHMT2) in BRC samples (n=1,222) and normal samples (n=113) derived from the TCGA portal by performing a BRC tissue microarray. EHMT2 overexpression was clearly associated with a poor prognosis in multiple cohorts of patients with BRC (total, n=1,644). Furthermore, the knockdown of EHMT2 expression affected cell apoptosis via the downregulation and re‑localization of heat shock protein family D (Hsp60) member 1 (HSPD1). In addition, a statistically significant positive correlation between EHMT2 and HSPD1 expression was revealed in the clinical cohorts. On the whole, the findings of this study may assist the development of novel therapeutic strategies and provide a prognostic marker (EHMT2) for patients with BRC.

摘要

乳腺癌(BRC)的分子分类,如人表皮生长因子受体2(HER2)、管腔A型和管腔B型,已被开发出来,通过将BRC患者分为低风险和高风险进展组来减少不必要的治疗。然而,这些方法并未涵盖BRC的所有病理特征,因此持续需要对新的预后/治疗标志物进行研究。在本研究中,我们通过制作BRC组织微阵列,确定了来自TCGA数据库的BRC样本(n = 1222)和正常样本(n = 113)中组蛋白甲基转移酶——常染色质组蛋白赖氨酸N - 甲基转移酶2(EHMT2)的过表达。EHMT2过表达与多个BRC患者队列(总计n = 1644)的不良预后明显相关。此外,EHMT2表达的敲低通过热休克蛋白家族D(Hsp60)成员1(HSPD1)的下调和重新定位影响细胞凋亡。此外,在临床队列中,EHMT2与HSPD1表达之间显示出具有统计学意义的正相关。总体而言,本研究结果可能有助于开发新的治疗策略,并为BRC患者提供一种预后标志物(EHMT2)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4d/6254934/c75c3c72c87b/IJO-54-01-0065-g00.jpg

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