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CIAPIN1 的下调通过抑制 STAT3 通路调节乳腺癌细胞的增殖、迁移和糖酵解。

Downregulation of CIAPIN1 regulates the proliferation, migration and glycolysis of breast cancer cells via inhibition of STAT3 pathway.

机构信息

Department of Breast and Thyroid Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong New Area, Shanghai, 201399, China.

Department of Pathology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

Sci Rep. 2024 Sep 5;14(1):20794. doi: 10.1038/s41598-024-71405-3.

Abstract

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.

摘要

细胞因子诱导凋亡抑制剂 1(CIAPIN1)是一种调节细胞凋亡和程序性细胞死亡的蛋白质。本研究旨在评估其抑制乳腺癌细胞增殖、迁移和糖酵解的潜力,并揭示其潜在的分子机制。我们从 2019 年 1 月至 2023 年 6 月在我院收集了 8 名乳腺癌患者的组织样本,以分析 CIAPIN1 的表达。我们用 CIAPIN1 的 siRNA 转染人乳腺癌细胞系(MCF7、MDA-MB-231、MDA-MB-453 和 MDA-MB-468)。最后,我们通过 RT-qPCR 和 Western blot 确定蛋白质表达。CIAPIN1 在乳腺癌组织和血清中表达上调。在 MCF7 和 MDA-MB-468 乳腺癌细胞系中检测到 CIAPIN1 的过表达。此外,CIAPIN1 过表达增加了细胞增殖和迁移率。CIAPIN1 下调抑制了乳腺癌细胞的增殖,同时增加了细胞凋亡、活性氧(ROS)产生和氧化应激。此外,CIAPIN1 抑制显著抑制了丙酮酸、乳酸和三磷酸腺苷(ATP)的产生,并降低了乳腺癌细胞中丙酮酸激酶 M2(PKM2)蛋白表达和信号转导和转录激活因子 3(STAT3)的磷酸化。下调 CIAPIN1 通过抑制 STAT3/PKM2 通路抑制乳腺癌细胞的增殖、迁移和糖酵解能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc94/11379703/619dde563400/41598_2024_71405_Fig1_HTML.jpg

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