Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, People's Republic of China.
Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, People's Republic of China.
Biomed Pharmacother. 2019 Jul;115:108947. doi: 10.1016/j.biopha.2019.108947. Epub 2019 May 8.
Breast cancer is the most common malignancy in women all over the world. MiRNAs are a type of small noncoding RNA that can regulate various cellular processes via binding different target genes in cancer cells. In this study, we found that miR-128-3p could suppress cellular proliferation and motility abilities of breast cancer. In addition, we found that overexpression of miR-128-3p arrested breast cancer cells in G0/G1 phase by affecting expression of CDK4/CDK6/Cyclin D1 and CDK2/Cyclin E1. Furthermore, we confirmed that LIM domain kinase 1 (LIMK1) is a direct target gene of miR-128-3p and that overexpression of miR-128-3p could suppress the expression levels of LIMK1 and Cofilin 1, which is downstream of LIMK1. TCGA clinical database showed that miR-128-3p was highly expressed in breast cancer patients and that high expression of miR-128-3p indicates a better prognosis of breast cancer. Our findings demonstrated that miR-128-3p could regulate cellular progression of breast cancer via regulating the LIMK1/CFL1 signaling pathway, and this new avenue could broaden existing versions of molecular mechanisms in breast cancer and perhaps represent potential novel direction of breast cancer treatment in the future.
乳腺癌是全世界女性最常见的恶性肿瘤。miRNAs 是一类小型非编码 RNA,可以通过结合癌细胞中不同的靶基因来调节各种细胞过程。在这项研究中,我们发现 miR-128-3p 可以抑制乳腺癌细胞的增殖和迁移能力。此外,我们发现 miR-128-3p 通过影响 CDK4/CDK6/Cyclin D1 和 CDK2/Cyclin E1 的表达,将乳腺癌细胞阻滞在 G0/G1 期。此外,我们证实 LIM 结构域激酶 1(LIMK1)是 miR-128-3p 的直接靶基因,过表达 miR-128-3p 可以抑制 LIMK1 和 LIMK1 下游的 Cofilin 1 的表达水平。TCGA 临床数据库显示,miR-128-3p 在乳腺癌患者中高表达,miR-128-3p 的高表达预示着乳腺癌的预后较好。我们的研究结果表明,miR-128-3p 可以通过调节 LIMK1/CFL1 信号通路来调节乳腺癌细胞的进展,这一新途径可能拓宽了乳腺癌现有分子机制的版本,并可能代表未来乳腺癌治疗的潜在新方向。