Downregulation of MiD49 contributes to tumor growth and metastasis of human pancreatic cancer

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.