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RNA 干扰靶向 CD147 通过下调 MMP-9/VEGF 的表达抑制人乳腺癌 MCF-7 细胞的转移和侵袭。

RNA interference targeting CD147 inhibits metastasis and invasion of human breast cancer MCF-7 cells by downregulating MMP-9/VEGF expression.

机构信息

Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, China.

Department of Oncology, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2018 Jul 1;50(7):676-684. doi: 10.1093/abbs/gmy062.

Abstract

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.

摘要

乳腺癌是最常见的恶性肿瘤之一。有必要确定新的标志物来预测肿瘤进展和治疗分子靶点。据报道,CD147 是原发性肿瘤和转移细胞中表达最广泛的蛋白之一。在本研究中,我们研究了 CD147 在人乳腺癌转移和侵袭中的作用,并探讨了其潜在的分子机制。免疫组化结果显示 CD147 在人乳腺癌组织中高表达,与乳腺癌的恶性程度呈正相关。用 CD147 siRNA 真核表达载体转染 MCF-7 细胞,导致 CD147 显著下调。我们发现 CD147 siRNA 可显著抑制细胞增殖、转移和侵袭。此外,我们的结果表明,CD147 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)没有明显影响。此外,CD147 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 CD147 通过调节 MMP-9 和 VEGF 的表达促进乳腺癌细胞的增殖、转移和侵袭。因此,CD147 可作为判断乳腺癌恶性行为的重要指标,可能成为乳腺癌治疗的潜在新靶点。

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