Changjiang Scholar's Laboratory/Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Shantou University Medical College, 515041, Shantou, China.
Department of General Surgery, the First Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China.
Cell Death Dis. 2020 Oct 24;11(10):912. doi: 10.1038/s41419-020-03121-5.
As important modulators in multiple physiological processes, microRNAs (miRNAs) have been reported in various malignant tumors, including breast cancer. The current study investigated the function of a new tumor suppressor microRNA, miR-488, and its molecular mechanism of metastasis in breast cancers. CCK8 and transwell assays revealed that the upregulated miR-488 level significantly inhibited the proliferation and migration of breast cancer cells. As a potential downstream gene, the mRNA and protein level of FSCN1 was suppressed by increased miR-488 and vice versa. Luciferase assay showed that miR-488 directly bind to the 3'UTR of FSCN1 and suppressed the translation process of FSCN1. The promoter region of miR-488 was directly bound by Notch3 and promoted the expression of miR-488 transcriptionally. Immunohistochemistry results revealed that in patients with breast cancer, the expression of Notch3 and were negatively correlated with the FSCN1 levels significantly. Therefore, the current finding predicted miR-488 as a tumor suppressor molecule in breast cancer, and demonstrated that Notch3/miR-488/FSCN1 axis is established and involved in regulating the metastasis of breast cancers, providing novel therapeutic targets for patients with breast cancers.
作为多种生理过程中的重要调节剂，microRNAs（miRNAs）已在多种恶性肿瘤中被报道，包括乳腺癌。本研究探讨了一种新的肿瘤抑制性 microRNA，miR-488，及其在乳腺癌转移中的分子机制。CCK8 和 Transwell 检测显示，上调的 miR-488 水平显著抑制乳腺癌细胞的增殖和迁移。作为一个潜在的下游基因，FSCN1 的 mRNA 和蛋白水平被上调的 miR-488 抑制，反之亦然。荧光素酶报告基因检测显示，miR-488 可直接结合 FSCN1 的 3'UTR，抑制 FSCN1 的翻译过程。miR-488 的启动子区域可被 Notch3 直接结合，从而促进 miR-488 的转录表达。免疫组化结果显示，在乳腺癌患者中，Notch3 和的表达与 FSCN1 水平呈显著负相关。因此，本研究预测 miR-488 是乳腺癌的肿瘤抑制分子，并证实 Notch3/miR-488/FSCN1 轴的建立并参与调节乳腺癌的转移，为乳腺癌患者提供了新的治疗靶点。
