Journal
CELL DEATH & DISEASE
Volume 8, Issue -, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/cddis.2017.205
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Funding
- National Natural Science Foundation of China [81672896, 81602071]
- Jiangsu Province Clinical Science and Technology projects (Clinical Research Center) [BL2012008]
- Natural Science Foundation of Jiangsu Province for Youth [BK20161066]
- Science Foundation of Jiangsu Province for Youth [BK20161066]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine) [JX10231801]
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Recent evidence indicates that E2F1 transcription factor have pivotal roles in the regulation of cellular processes, and is found to be dysregulated in a variety of cancers. Long non-coding RNAs (lncRNAs) are also reported to exert important effect on tumorigenesis. E2F1 is aberrantly expressed in gastric cancer (GC), and biology functions of E2F1 in GC are controversial. The biological characteristics of E2F1 and correlation between E2F1 and lncRNAs in GC remain to be found. In this study, integrated analysis revealed that E2F1 expression was significantly increased in GC cases and its expression was positively correlated with the poor pathologic stage, large tumor size and poor prognosis. Forced E2F1 expression promotes proliferation, whereas loss of E2F1 function decreased cell proliferation by blocking of cell cycle in GC cells. Mechanistic analyses indicated that E2F1 accelerates GC growth partly through induces TINCR transcription. TINCR could bind to STAU1 (staufen1) protein, and influence CDKN2B mRNA stability and expression, thereby affecting the proliferation of GC cells. Together, our findings suggest that E2F1/TINCR/STAU1/CDKN2B signaling axis contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.
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