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Exosome miR-134-5p restrains breast cancer progression via regulating PI3K/AKT pathway by targeting ARHGAP1

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机构: [1]Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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关键词: ARHGAP1 breast cancer exosome miR-134-5p

摘要:
Aim Exosomes has been shown to be involved in the regulation of cancer progression. However, the role of exosome miR-134-5p in breast cancer (BC) progression is unclear. Methods Exosomes were extracted from BC cells (MCF-7 and MDA-MB-231) using differential centrifugation and were observed by transmission electron microscope (TEM). The protein levels of exosome markers, apoptosis markers, Rho GTPase activating protein 1 (ARHGAP1, an important oncogene in BC) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) markers were detected by western blot (WB) assay. Quantitative real-time PCR was used to measure the expression levels of miR-134-5p and ARHGAP1. Cell cycle and apoptosis, colony number, viability, migration, and invasion were determined by flow cytometry, colony formation assay, MTT assay, and transwell assay, respectively. The interaction between miR-134-5p and ARHGAP1 was confirmed using a dual-luciferase reporter assay. Xenograft models were constructed to verify the role of exosome miR-134-5p in BC tumor growth in vivo. Results MiR-134-5p was lowly expressed in BC cells and in the exosomes of BC cells. Overexpressed exosome miR-134-5p suppressed the proliferation, migration, invasion, and promoted the apoptosis of BC cells. ARHGAP1 was a target of miR-134-5p, and its silencing could inhibit BC progression. In addition, ARHGAP1 overexpression could reverse the negative regulation of miR-134-5p on BC progression. MiR-134-5p could target ARHGAP1 to inhibit the activity of PI3K/AKT pathway. Exosome miR-134-5p overexpression could suppress BC tumor growth via targeting ARHGAP1 in vivo. Conclusion Exosome miR-134-5p restrained BC progression through regulating ARHGAP1/PI3K/AKT signaling pathway, suggesting that miR-134-5p might be a therapeutic target for BC.

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出版当年[2021]版:
大类 | 4 区 医学
小类 | 4 区 妇产科学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 妇产科学
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出版当年[2021]版:
Q4 OBSTETRICS & GYNECOLOGY
最新[2024]版:
Q3 OBSTETRICS & GYNECOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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通讯机构: [1]Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China [*1]Department of Breast Center, The Fourth Hospital of Hebei Medical University, 169 Tianshan Street, Shijiazhuang, 050000, Hebei, China.
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