Department of Oncology, Huai'an Hospital, Xuzhou Medical University, Huai'an 223002, China.
Department of laboratory, Huaiyin Hospital of huai'an city, Huai'an 223300, China.
Biomed Pharmacother. 2017 Feb;86:426-433. doi: 10.1016/j.biopha.2016.12.051. Epub 2016 Dec 21.
MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes, which played a vital role in regulation cancer cells epithelial-to-mesenchymal transition and metastasis. The deregulation of miR-381 has been identified in breast cancer. However, the role and mechanism of miR-381 in breast cancer have not been completely unexplored.
Total RNA was extracted from the tissues of 27 patients with breast cancer and two breast cancer cell lines, respectively. The expression levels of miR-381 were examined by quantitative real-time PCR. The stable overexpress or silence miR-381 expression cells lines and control cells line were constructed by lentivirus infection. Subsequently, cell proliferation, cell migration, invasion assay and western blot assay were performed to detect the biological functions of miR-381 in vitro. Moreover, a luciferase reporter assay was conducted to confirm target associations.
In this study, we validated the lower expression of miR-381 in breast cancer tissues than their adjacent non-neoplastic tissues in 27 breast cancer patients. The result also showed that miR-381 was lowly expressed in breast cancer cell lines MCF-7 and MDA-MB-231 than human epithelial cell line MCF-10A. The miR-381 expression was significantly up-regulated under exogenous miRNA-381 treatment in MCF-7 and MDA-MB-231 cells analyzed by quantitative real-time PCR. The results also indicated that an inverse correlation existed between miR-381 expression level and breast cancer cell proliferation, epithelial-to-mesenchymal transition and metastasis. Furthermore, miR-381 was predicted as a regulatory miRNA of CXCR4 in breast cancer, and the data analysis revealed that there was a negatively relationship between miR-381 and CXCR4 expression in breast cancer tissues from the patients. miR-381 played an important role in breast cancer cells proliferation, epithelial-to-mesenchymal transition and metastasis by targeting CXCR4.
This present study revealed that miR-381 might be considered as a novel therapeutic target for breast cancer treatment.
MicroRNAs 在许多生物过程中作为基因表达的转录后调节剂发挥作用，在调节癌细胞上皮-间充质转化和转移方面发挥着重要作用。miR-381 的失调已在乳腺癌中被鉴定出来。然而，miR-381 在乳腺癌中的作用和机制尚未完全被探索。
分别从 27 名乳腺癌患者和两种乳腺癌细胞系的组织中提取总 RNA。通过定量实时 PCR 检测 miR-381 的表达水平。通过慢病毒感染构建稳定过表达或沉默 miR-381 表达的细胞系和对照细胞系。随后，进行细胞增殖、细胞迁移、侵袭测定和 Western blot 测定，以检测 miR-381 在体外的生物学功能。此外，进行了荧光素酶报告基因测定以确认靶标关联。
在这项研究中，我们在 27 名乳腺癌患者中验证了 miR-381 在乳腺癌组织中的表达低于其相邻非肿瘤组织。结果还表明，miR-381 在乳腺癌细胞系 MCF-7 和 MDA-MB-231 中的表达低于人上皮细胞系 MCF-10A。通过定量实时 PCR 分析，外源性 miRNA-381 处理后 MCF-7 和 MDA-MB-231 细胞中的 miR-381 表达明显上调。结果还表明，miR-381 表达水平与乳腺癌细胞增殖、上皮-间充质转化和转移呈负相关。此外，miR-381 被预测为乳腺癌中 CXCR4 的调节 miRNA，数据分析显示，患者乳腺癌组织中 miR-381 和 CXCR4 的表达呈负相关。miR-381 通过靶向 CXCR4 在乳腺癌细胞增殖、上皮-间充质转化和转移中发挥重要作用。
本研究表明，miR-381 可能被认为是乳腺癌治疗的一种新的治疗靶点。
