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MST1 通过调控 Hippo 信号通路抑制乳腺癌的进展,有望成为一种预后生物标志物。

MST1 inhibits the progression of breast cancer by regulating the Hippo signaling pathway and may serve as a prognostic biomarker.

机构信息

Department of Breast Surgery, The First People's Hospital of Yibin, Yibin, Sichuan 644000, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12022. Epub 2021 Mar 24.

Abstract

Breast cancer (BCa) is the most common malignancy threatening the health of women worldwide, and the incidence rate has significantly increased in the last 10 years. Mammalian STE20‑like protein kinase 1 (MST1) is involved in the development of various types of malignant tumor. The present study aimed to investigate the role of MST1 in BCa and its potential involvement in the poor prognosis of patients with BCa. Reverse transcription‑quantitative PCR and immunohistochemistry were used to analyze the expression levels of MST1 in BCa, and the clinicopathological characteristics and prognosis of patients with BCa were further analyzed by statistical analysis. MST1 was overexpressed in BCa cell lines (MCF‑7, MDA‑MB‑231 and SKBR3). Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and flow cytometry assays were used to analyze cell proliferation and apoptosis, respectively, and a wound healing assay was used to analyze cell migration. The results of the present study revealed that the downregulated expression levels of MST1 in BCa were closely associated with the poor prognosis of patients, and MST1 may be an independent risk factor for BCa. The overexpression of MST1 significantly inhibited the proliferation and migration, and promoted the apoptosis of BCa cells. In addition, the overexpression of MST1 significantly activated the Hippo signaling pathway. Treatment with XMU‑MP‑1 downregulated the expression levels of MST1 and partially reversed the inhibitory effects of MST1 on proliferation, migration and apoptosis‑related proteins, and inhibited the Hippo signaling pathway. In conclusion, the results of the present study suggested that MST1 expression levels may be downregulated in BCa and closely associated with tumor size and clinical stage, as well as the poor prognosis of affected patients. Furthermore, MST1 may inhibit the progression of BCa by targeting the Hippo signaling pathway.

摘要

乳腺癌(BCa)是全球威胁女性健康的最常见恶性肿瘤,在过去 10 年中其发病率显著增加。哺乳动物 STE20 样蛋白激酶 1(MST1)参与多种类型恶性肿瘤的发生发展。本研究旨在探讨 MST1 在 BCa 中的作用及其是否与 BCa 患者不良预后有关。采用反转录-定量 PCR 和免疫组织化学方法分析 BCa 中 MST1 的表达水平,通过统计学分析进一步分析 BCa 患者的临床病理特征和预后。MST1 在 BCa 细胞系(MCF-7、MDA-MB-231 和 SKBR3)中过表达。细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷和流式细胞术分别用于分析细胞增殖和凋亡,划痕愈合实验用于分析细胞迁移。本研究结果表明,BCa 中 MST1 表达水平下调与患者预后不良密切相关,MST1 可能是 BCa 的独立危险因素。过表达 MST1 可显著抑制 BCa 细胞的增殖和迁移,并促进其凋亡。此外,过表达 MST1 可显著激活 Hippo 信号通路。XMU-MP-1 处理可下调 MST1 的表达水平,并部分逆转 MST1 对增殖、迁移和凋亡相关蛋白的抑制作用,抑制 Hippo 信号通路。综上所述,本研究结果表明,MST1 表达水平可能在 BCa 中下调,与肿瘤大小和临床分期以及患者不良预后密切相关。此外,MST1 可能通过靶向 Hippo 信号通路抑制 BCa 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c65/7986037/289efe3d1578/mmr-23-05-12022-g00.jpg

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