Department of Breast Surgery.
Department of Respiratory Medicine.
Acta Pharmacol Sin. 2018 Jan;39(1):124-131. doi: 10.1038/aps.2017.89. Epub 2017 Aug 17.
Dysregulation of microRNAs (miRNAs) has been implicated in cancer. Recently, miR-132 has been reported to be downregulated in the tissues of patients with breast cancer. In this study, we investigated the functional role of miR-132 and its direct target FOXA1 in breast cancer cells. In 30 human breast cancer tissues, FOXA1 was significantly overexpressed and negatively correlated with miR-132 expression. A bioinformatics analysis suggested that FOXA1 was a potential target of miR-132. Furthermore, dual luciferase reporter assays revealed that miR-132 dose-dependently inhibited the luciferase activity of the wt 3'UTR of FOXA1 rather than the mut 3'UTR of FOXA1 in human MDA-MB-468 and SK-BR3 breast cancer cells. Moreover, ectopic miR-132 expression significantly inhibited FOXA1 protein expression, whereas miR-132 knockdown promoted FOXA1 expression in the breast cancer cells. Ectopic miR-132 expression also suppressed proliferation of the breast cancer cells, whereas miR-132 knockdown promoted proliferation of the breast cancer cells, which was reversed by knockdown of FOXA1 expression. We conclude that MiR-132 suppresses proliferation of breast cancer cells at least partially though inhibition of FOXA1. These results suggest that miR-132 and FOXA1 may be potential biomarkers or therapeutic targets in breast cancer.
miRNAs(miRNAs)的失调与癌症有关。最近,有报道称 miR-132 在乳腺癌患者的组织中下调。在这项研究中,我们研究了 miR-132 及其在乳腺癌细胞中的直接靶标 FOXA1 的功能作用。在 30 个人乳腺癌组织中,FOXA1 显著过表达,并与 miR-132 的表达呈负相关。生物信息学分析表明,FOXA1 是 miR-132 的一个潜在靶标。此外,双荧光素酶报告基因检测显示,miR-132 以剂量依赖性方式抑制人 MDA-MB-468 和 SK-BR3 乳腺癌细胞中 FOXA1 的 wt 3'UTR 的荧光素酶活性,而不是 FOXA1 的 mut 3'UTR。此外,外源性 miR-132 表达显著抑制 FOXA1 蛋白表达,而 miR-132 敲低促进乳腺癌细胞中 FOXA1 的表达。外源性 miR-132 表达还抑制乳腺癌细胞的增殖,而 miR-132 敲低促进乳腺癌细胞的增殖,FOXA1 表达的敲低可逆转这一作用。我们得出结论,miR-132 通过抑制 FOXA1 至少部分地抑制乳腺癌细胞的增殖。这些结果表明,miR-132 和 FOXA1 可能是乳腺癌的潜在生物标志物或治疗靶点。