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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
- Source :
- Oncogene
- Publication Year :
- 2020
-
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.
- 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
Subjects
Details
- ISSN :
- 14765594
- Volume :
- 39
- Issue :
- 38
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....85f1aa1d6cab3bf586dd82a635ade68d