期刊
AGING-US
卷 14, 期 5, 页码 2268-2286出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.203934
关键词
FOX; HCC; FOXH1; prognosis; cell invasion
资金
- National Nature Science Foundation of China [81372631]
- Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province [CXPJJH11800001-2018208]
- National Natural Science Foundation of China [81903004]
This study provides comprehensive evaluation of the clinical value of FOX proteins in HCC and experimental evidence supporting the role of FOXH1 in HCC development. The findings suggest that FOXH1 promotes cell growth and migration/invasion in HCC through mTOR signaling. These results contribute to the development of more effective therapies for HCC patients.
Hepatocellular carcinoma (HCC) remains the second leading cause of cancer related deaths worldwide. Understanding about the molecular biology of HCC and development of targeted therapies are still the main focuses of this type of disease. Here, by connecting the expression levels of FOX proteins with their associated clinical characteristics using TCGA LIHC dataset, we found that 27/40 FOX proteins were highly expressed in HCC tumors compared to normal liver tissues and their expression levels were tightly associated with HCC tumor stage, tumor grade and overall survival. Our experimental results also confirmed that FOXH1 indeed played an oncogenic role in HCC development by promoting cell growth and cell migration/invasion. Mechanistic dissection demonstrated that FOXH1-induced cell growth and cell migration/invasion relied on mTOR signaling because inhibition of mTOR signaling by rapamycin could attenuate FOXH1-mediated phenotypic alterations of HCC cells. The results from orthotopic mouse model also validated that FOXH1 promoted HA22T tumor growth via triggering mTOR activation. Overall, this study not only comprehensively examines the clinical values of FOX proteins in HCC but also provides experimental evidence to support the role of FOXH1 in HCC development, building rationale to develop more effective therapies to treat HCC patients.
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