Shui Yifang, Yu Xiaojing, Duan Rui, Bao Qianyi, Wu Jiahui, Yuan Hongyan, Ma Changyan
Department of Developmental Genetics, Nanjing Medical University, Longmian Road101, Nanjing 211166, P.R. China.
Department of Oncology and Lombardi Comprehensive Cancer Center, Lombardi Comprehensive Cancer Center, Washington, DC 20007, USA.
Gene. 2017 Apr 20;609:80-87. doi: 10.1016/j.gene.2017.01.036. Epub 2017 Feb 3.
Breast carcinoma is the most common malignancy in women, and the incidence rate has increased dramatically in recent years. Metastasis is responsible for most advanced breast cancer mortality, but the underlying mechanisms remain poorly understood despite extensive research. Recently, short non-coding RNA molecules, including miRNAs, which mediate changes in signalling pathways, have emerged as metastatic regulators of the breast carcinoma. Previous reports have suggested that miR-130b-3p has both oncogenic and tumour suppressor functions in a cancer type-dependent manner. However, the roles and underlying molecular mechanisms of miR-130b-3p in the development of metastasis in breast carcinoma remain unclear. Here, we reported for the first time that miR-130b-3p was differentially expressed in early-stage non-invasive MCF-7 human breast carcinoma cells and aggressive late-stage MDA-MB-231 cells. In gain-of-function and loss-of-function studies, we demonstrated that miR-130b-3p could inhibit breast carcinoma cell invasion and migration by directly targeting the Notch ligand Delta-like 1 (DLL1). Our data also indicated that MMP-9, MMP-13, and VEGF were regulated by miR-130b-3p and may be involved in the inhibition of cell invasion and migration in breast carcinoma. Collectively, our findings reveal a new regulatory mechanism of miR-130b-3p and suggest that miR-130b-3p may be a potential target against human breast cancer metastasis.
乳腺癌是女性中最常见的恶性肿瘤,近年来其发病率急剧上升。转移是大多数晚期乳腺癌死亡的原因,但尽管进行了广泛研究,其潜在机制仍知之甚少。最近,包括miRNA在内的短非编码RNA分子作为乳腺癌转移的调节因子出现,它们介导信号通路的变化。先前的报道表明,miR-130b-3p在癌症类型依赖性方面具有致癌和肿瘤抑制功能。然而,miR-130b-3p在乳腺癌转移发展中的作用和潜在分子机制仍不清楚。在这里,我们首次报道miR-130b-3p在早期非侵袭性MCF-7人乳腺癌细胞和侵袭性晚期MDA-MB-231细胞中差异表达。在功能获得和功能丧失研究中,我们证明miR-130b-3p可通过直接靶向Notch配体Delta样1(DLL1)来抑制乳腺癌细胞的侵袭和迁移。我们的数据还表明,MMP-9、MMP-13和VEGF受miR-130b-3p调节,可能参与抑制乳腺癌细胞的侵袭和迁移。总的来说,我们的研究结果揭示了miR-130b-3p的一种新的调节机制,并表明miR-130b-3p可能是对抗人类乳腺癌转移的潜在靶点。