Downregulation of MiD49 contributes to tumor growth and metastasis of human pancreatic cancer
Downregulation of MiD49 contributes to tumor growth and metastasis of human pancreatic cancer
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DOI：
10.3892/or.2020.7499
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发表时间：
2020-04-01
期刊：
影响因子：
4.2
通讯作者：
Li, Enxiao
中科院分区：
文献类型：
--
作者：
Bai, Lu;Liang, Jing;Li, Enxiao
线粒体分裂融合蛋白失控引起的线粒体形态改变越来越被认为是癌症的标志。MiD49(线粒体动力学蛋白49 kDa)是新近发现的一种参与线粒体形态动态调节的线粒体分裂蛋白。然而，MiD49在人类肿瘤，特别是在胰腺癌中的表达模式和生物学功能仍未得到很大的研究。本研究首先采用RT-qPCR和免疫印迹方法检测了MiD49在PC细胞系和肿瘤组织中的表达及其临床意义。此外，通过体外和体内功能获得和功能丧失的分析，研究了MiD49在PC细胞生长和转移中的生物学功能。此外，进一步探讨了miD49调控PC细胞生长和转移的潜在机制。结果表明，MiD49在PC细胞系和人PC标本中均显著下调。在体内外，强制表达miD49抑制PC细胞的生长和转移，而敲除miD49则表现出相反的作用。机制研究表明，MiD49的肿瘤抑制作用是通过减少线粒体分裂和随后减少PC细胞中ROS的产生来实现的。我们的发现表明MiD49在胰腺癌中发挥了关键的肿瘤抑制作用。
Changes in mitochondrial morphology by dysregulated mitochondrial fission-fusion proteins have been increasingly recognized as a hallmark of cancer. MiD49 (mitochondrial dynamics protein of 49 kDa) is a newly identified mitochondrial fission protein involved in the dynamic regulation of mitochondrial morphology. However, the expression pattern and biological functions of MiD49 in human cancers remain largely unexplored, especially in pancreatic cancer (PC). In the present study, the expression and clinical significance of MiD49 was firstly determined by RT-qPCR and western blot analyses in PC cell lines and tumor tissues. In addition, the biologic functions of MiD49 in PC cell growth and metastasis were investigated using gain- and loss-of-function assays both in vitro and in vivo. Moreover, the underlying mechanisms by which MiD49 regulates PC cell growth and metastasis were further explored. Our results showed that MiD49 was markedly downregulated in both PC cell lines and human PC specimens. Forced expression of MiD49 suppressed PC cell growth and metastasis both in vitro and in vivo, while knockdown of MiD49 exhibited the opposite effect. Mechanistic exploration demonstrated that the tumor-suppressive effect of MiD49 was mediated by decreased mitochondrial fission and subsequent reduced ROS production in PC cells. Our findings suggest a critical tumor-suppressive role played by MiD49 in pancreatic cancer.