Zhu Xiaoliang, Rao Xuefeng, Yao Wu, Zou Xia
Department of General Surgery, Jiangxi Provincial People's Hospital Nanchang 330006, People's Republic of China.
Am J Transl Res. 2018 Oct 15;10(10):3122-3132. eCollection 2018.
Breast cancer is considered to be the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) play key roles in the regulation of tumor properties based on their capacity to regulate the expression of tumor-related genes. However, the involvement of miR-196b-5p in breast cancer development is largely unknown. Here, we showed that the expression levels of miR-196b-5p were significantly down-regulated in breast cancer samples and cell lines compared to the matched normal tissues and breast epithelial cell line, respectively. Notably, the expression of miR-196b-5p was negatively associated with lymph node metastasis and the progression of clinical stage in patients with breast cancer. MiR-196b-5p over-expression significantly inhibited the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells in breast cancer. Furthermore, combining bioinformatics prediction and biochemical analyses, we showed that COL1A1 (collagen type I alpha 1 chain) was a direct downstream target gene of miR-196b-5p. Furthermore, overexpression of COL1A1 partly abrogated miR-196b-5p-mediated inhibition of proliferation and migration in MDA-MB-231 and MDA-MB-468 cells. Our data collectively indicate that miR-196b-5p inhibits cell growth and metastasis in breast cancer through down-regulating COL1A1, supporting the targeting of the new miR-196b-5p/COL1A1 axis as a promising effective therapeutic approach for breast cancer.
乳腺癌被认为是全球女性中最常被诊断出的恶性肿瘤。微小RNA（miRNA）基于其调节肿瘤相关基因表达的能力，在肿瘤特性的调节中发挥关键作用。然而，miR-196b-5p在乳腺癌发展中的作用在很大程度上尚不清楚。在此，我们发现与匹配的正常组织和乳腺上皮细胞系相比，miR-196b-5p在乳腺癌样本和细胞系中的表达水平分别显著下调。值得注意的是，miR-196b-5p的表达与乳腺癌患者的淋巴结转移和临床分期进展呈负相关。miR-196b-5p过表达显著抑制乳腺癌中MDA-MB-231和MDA-MB-468细胞的增殖和迁移。此外，结合生物信息学预测和生化分析，我们发现COL1A1（I型胶原α1链）是miR-196b-5p的直接下游靶基因。此外，COL1A1的过表达部分消除了miR-196b-5p介导的对MDA-MB-231和MDA-MB-468细胞增殖和迁移的抑制作用。我们的数据共同表明，miR-196b-5p通过下调COL1A1抑制乳腺癌细胞的生长和转移，支持将新的miR-196b-5p/COL1A1轴作为一种有前景的乳腺癌有效治疗方法的靶点。
