期刊
ONCOTARGET
卷 7, 期 10, 页码 11284-11298出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7022
关键词
cell proliferation; liver cancer; RNA polymerase II; promoter; survival
资金
- National Natural Science Foundation of China [81301689, 81201913, 81202958]
- Yangfan Project of the Shanghai Science and Technology Commission [14YF1412300]
- China Central Colleges and Universities basic research-specific cross discipline grant [1501219096]
- Outstanding Youth Training Program of Tongji University [1501219080]
- Shanghai Tenth People's Hospital climbing training program [04.01.13024]
- Shanghai Jiaotong University School of Medicine outstanding young teacher grant
- Young College Teachers' Training Scheme of Shanghai [ZZjdyx13007]
Both oncoprotein and tumor-suppressor activity have been reported for SIRTUIN1 (SIRT1) and p38 in many types of cancer. The effect of SIRT1 on p38 phosphorylation (p-p38) remains controversial and may be organ- and cell-specific. We found that SIRT1 is essential for maintaining liver size and weight in mice. SIRT1 levels were elevated in human HCC compared to adjacent normal liver tissue, and its expression correlated positively with p-p38 levels. Additionally, SIRT1-activated p38 increased liver cancer malignancy. SIRT1 increased phosphorylation and nuclear accumulation of p38, possibly by increasing MKK3 expression. SIRT1 also induced YAP expression, which in turn increased MKK3 transcription. Positive correlations between SIRT1, YAP, MKK3, and p-p38 levels indicate that blocking their activity may prove helpful in treating HCC.
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