RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression
RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression
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DOI：
10.1093/abbs/gmy062
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发表时间：
2018-07-01
影响因子：
3.7
通讯作者：
Wang, Zhuanhua
中科院分区：
文献类型：
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作者：
Li, Fang;Zhang, Junping;Wang, Zhuanhua
乳腺癌是最常见的恶性肿瘤之一。因此，有必要寻找新的肿瘤进展预测标志物和治疗分子靶点。据报道，CD 147是原发性肿瘤和转移性细胞中最常表达的蛋白质之一。在这项研究中，我们研究了CD 147在人类乳腺癌转移和侵袭中的作用，并研究了其潜在的分子机制。免疫组化结果显示CD 147在乳腺癌组织中呈高表达，与乳腺癌的恶性程度呈正相关。用CD 147 siRNA真核表达载体转染MCF-7细胞，其导致CD 147的显著敲低。我们发现，CD 147 siRNA显着抑制细胞增殖，转移和侵袭。此外，我们的结果表明，CD 147 siRNA抑制基质金属蛋白酶9（MMP-9）的合成，但对基质金属蛋白酶2（MMP-2）没有显着影响。此外，CD 147 siRNA显著抑制血管内皮生长因子（VEGF）的产生。综上所述，这些数据表明，CD 147通过调节MMP-9和VEGF表达促进乳腺癌细胞增殖、转移和侵袭。因此，CD 147可能作为判断乳腺癌恶性行为的重要指标，并可能成为乳腺癌治疗的潜在新靶点。
Breast cancer is one of the most common malignancies. It is necessary to identify new markers for predicting tumor progression and therapeutic molecular targets. It has been reported that CD147 is one of the most commonly expressed proteins in primary tumors and in metastatic cells. In this study, we investigated the role of CD147 in human breast cancer metastasis and invasion, and examined its underlying molecular mechanisms. Immunohistochemistry results revealed high expression of CD147 in human breast tumor tissues, which was positively correlated with the malignancy of breast cancer. MCF-7 cells were transfected with CD147 siRNA eukaryotic expression vector, which resulted in significant knockdown of CD147. We found that CD147 siRNA dramatically inhibited cell proliferation, metastasis, and invasion. Furthermore, our results demonstrated that CD147 siRNA inhibited the synthesis of matrix metalloproteinase 9 (MMP-9) but had no significant effect on matrix metalloproteinase 2 (MMP-2). In addition, CD147 siRNA significantly inhibited the production of vascular endothelial growth factor (VEGF). Taken together, these data indicate that CD147 promotes breast cancer cell proliferation, metastasis, and invasion by modulating MMP-9 and VEGF expression. Thus, CD147 may be used as an important indicator for the judgment of malignant behavior of breast cancer, and may be a potential novel target for breast cancer therapy.