| 耿西林,常虎林,张 煜,海 军,张智勇,郑 伟,杜立学.MFN1在肝癌转移中的调控作用研究[J].,2019,19(9):1624-1628 |
| MFN1在肝癌转移中的调控作用研究 |
| Biological Function of MFN1 in the Metastasis of Hepatocellular Carcinoma Cells |
| 投稿时间：2018-08-23 修订日期：2018-09-18 |
| DOI：10.13241/j.cnki.pmb.2019.09.005 |
| 中文关键词: 线粒体 线粒体融合蛋白1 基质金属蛋白酶7 转移 肝癌 |
| 英文关键词: Mitochondria MFN1 MMP7 Metastasis Hepatocellular carcinoma |
| 基金项目:陕西省自然科学基础研究计划项目(2016JM8063)；国家自然科学基金青年科学项目(81502085) |
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| 中文摘要: |
| 摘要 目的：探讨线粒体融合蛋白MFN1(mito-fusion 1)在肝癌转移中的作用及其机制。方法：1).采用免疫组化实验检测15对肝癌转移灶组织与原发灶组织中MFN1的表达，以明确肝癌转移时是否伴有MFN1表达的改变。2).采用siRNA(small interference RNA)下调肝癌细胞中MFN1的表达后，提高Transwell迁移实验和Transwell侵袭实验分别检测其迁移和侵袭能力，通过实时荧光定量PCR(Quantitative Real-time PCR，qRT-PCR)和Western blot实验分别检测基质金属蛋白酶1(matrix metalloproteinase 1，MMP1)、MMP2、MMP7及MMP9的mRNA和蛋白表达。结果：1)肝癌转移灶组织中MFN1表达显著低于原发灶组织(P<0.05)。2).下调MFN1表达后，肝癌细胞的迁移和侵袭能力显著升高，MMP7的表达显著增加，而MMP1、MMP2与MMP9的表达无明显变化。结论：线粒体融合蛋白MFN1在肝癌转移组织中表达显著降低，可能通过激活MMP7表达,促进肝癌细胞侵袭和转移。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the role of the mitochondrial fusion MFN1 in the metastasis of hepatocellular carcinoma (HCC) cells. Methods: 1. Immunohistochemistry assay was used for evaluating the expression of MFN1 in 15 paired metastatic and pri- mary tissues of HCC to determine whether the expression of MFN1 was changed during metastasis. 2. After MFN1 was knocked-down in HCC cells by small interference RNA (siRNA), transwell migration and invasion assays were used to analyze the migration and invasion capabilities of HCC cells. qRT-PCR and western blot analysis were used for detection of expression levels of matrix metalloproteinase (MMPs) of MMP1, MMP2, MMP7 and MMP9. Results: The expression of MFN1 in metastatic tissues of HCC is significantly lower than their paired primary tissues. Knockdown of MFN1 upregulated the migration and invasion abilities, and the expression of MMP7 in HCC cells, while had no effect on the expressions of MMP1, MMP2 and MMP9. Conclusion: The expression of mitochondrial fission factor MFN1 is downregulated in metastatic tissues, which may promote the invasion and metastasis of HCC cells by upregulating of MMP7 expression. |
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