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

Bai,Lu; Liang,Jing; Li,Lihong; Li,Enxiao

doi:10.3892/or.2020.7499

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

Authors:
- Lu Bai
- Jing Liang
- Lihong Li
- Enxiao Li
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Affiliations: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Geriatric Respiration, Xi'an No. 1 Hospital, Xi'an, Shaanxi 710002, P.R. China
Published online on: February 12, 2020 https://doi.org/10.3892/or.2020.7499
Pages: 1208-1220
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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