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miR-27a 通过 GSK-3β 促进乳腺癌进展。

MiR-27a Facilitates Breast Cancer Progression via GSK-3β.

机构信息

Department of Clinical Laboratory, ShengLi Oilfield Central Hospital, Dongying, Shandong, China.

Department of Orthopedic Trauma, ShengLi Oilfield Central Hospital, Dongying, Shandong, China.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820965576. doi: 10.1177/1533033820965576.

Abstract

Breast cancer remains one of the leading causes of cancer-associated death in women. MiR-27a is highly expressed in breast cancer tissue. However, the underlying mechanisms that promote breast cancer progression are unknown. In this study, we investigated the regulatory mechanisms of miR-27a and its target glycogen Synthase Kinase 3-β (GSK-3β) in breast cancer cells. We found that miR-27a was highly expressed in breast cancer tissues, which downregulated GSK-3β expression. We further identified GSK-3β as a direct target of miR-27a, and found that the miR-27a mediated suppression of GSK-3β activated Wnt/β-catenin-associated proliferative and invasive factor in breast cancer. The cell transfection assay demonstrated the overexpression of miR-27a also enhanced cell proliferation and invasion, and reduced cell apoptosis through GSK-3β. Finally, we demonstrated that the overexpression of miR-27a facilitated breast cancer progression through its ability to down-regulate the phosphorylation of GSK-3β both and . These findings highlighted miR-27a as a novel therapeutic target in breast cancer.

摘要

乳腺癌仍然是女性癌症相关死亡的主要原因之一。miR-27a 在乳腺癌组织中高度表达。然而,促进乳腺癌进展的潜在机制尚不清楚。在这项研究中,我们研究了 miR-27a 及其靶糖原合酶激酶 3-β(GSK-3β)在乳腺癌细胞中的调节机制。我们发现 miR-27a 在乳腺癌组织中高表达,下调 GSK-3β 的表达。我们进一步确定 GSK-3β 是 miR-27a 的直接靶标,并发现 miR-27a 介导的 GSK-3β 抑制激活了乳腺癌中与 Wnt/β-连环蛋白相关的增殖和侵袭因子。细胞转染实验表明,miR-27a 的过表达也通过 GSK-3β 增强细胞增殖和侵袭,减少细胞凋亡。最后,我们证明 miR-27a 通过下调 GSK-3β 的磷酸化来促进乳腺癌的进展。这些发现强调了 miR-27a 作为乳腺癌治疗的新靶点的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a50/7545786/2657897d2e88/10.1177_1533033820965576-fig1.jpg

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