1. A novel mitochondrial amidoxime reducing component 2 is a favorable indicator of cancer and suppresses the progression of hepatocellular carcinoma by regulating the expression of p27
- Author
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Yifeng Cui, Bo Zhang, Hongrui Guo, Kun Ma, Jiabei Wang, Shuo Zhou, Guangchao Yang, Linmao Sun, Shugeng Zhang, Congyi Zhang, Yufeng Liu, Yao Liu, Lianxin Liu, Dehai Wu, Shuhang Liang, and Yan Wang
- Subjects
Male ,Cancer Research ,Mice ,Prognostic markers ,0302 clinical medicine ,Neoplasm Metastasis ,Regulation of gene expression ,0303 health sciences ,Liver Neoplasms ,Methylation ,Middle Aged ,Prognosis ,Mitochondria ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Disease Progression ,Female ,Signal transduction ,Oxidoreductases ,Liver cancer ,Cyclin-Dependent Kinase Inhibitor p27 ,Signal Transduction ,Adult ,Carcinoma, Hepatocellular ,Biology ,Article ,Mitochondrial Proteins ,03 medical and health sciences ,Cell Line, Tumor ,Genetics ,medicine ,Carcinoma ,Animals ,Humans ,Molecular Biology ,neoplasms ,030304 developmental biology ,Aged ,Cell Proliferation ,Hippo signaling pathway ,Cell growth ,Cancer ,Membrane Proteins ,medicine.disease ,Xenograft Model Antitumor Assays ,digestive system diseases ,Disease Models, Animal ,Cancer research ,Energy Metabolism - Abstract
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality in the United States. Exploring the mechanism of HCC and identifying ideal targets is critical. In the present study, we demonstrated metabolism dysfunction might be a key diver for the development of HCC. The mitochondrial amidoxime reducing component 2 (MARC2) as a newly discovered molybdenum enzyme was downregulated in human HCC tissues and HCC cells. Downregulated MARC2 was significantly associated with clinicopathological characteristics of HCC, such as tumor size, AFP levels, and tumor grade and was an independent risk factor of poor prognosis. Both in vitro and in vivo studies suggested that MARC2 suppressed the progression of HCC by regulating the protein expression level of p27. The Hippo signaling pathway and RNF123 were required for this process. Moreover, MARC2 regulated expression of HNF4A via the Hippo signaling pathway. HNF4A was recruited to the promoter of MARC2 forming a feedback loop. MARC2 levels were downregulated by methylation. We demonstrated the prognostic value of MARC2 in HCC and determined the mechanism by which MARC2 suppressed the progression of HCC in this study. These findings may lead to new therapeutic targets for HCC.
- Published
- 2020