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E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis.
- Source :
-
Cell death & disease [Cell Death Dis] 2017 Jun 01; Vol. 8 (6), pp. e2837. Date of Electronic Publication: 2017 Jun 01. - Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- Adenocarcinoma metabolism
Adenocarcinoma mortality
Adenocarcinoma pathology
Animals
Carcinogenesis genetics
Carcinogenesis metabolism
Carcinogenesis pathology
Cell Cycle Checkpoints
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p15 metabolism
Cytoskeletal Proteins metabolism
Disease Progression
E2F1 Transcription Factor metabolism
Humans
Mice
Mice, Nude
Neoplasm Transplantation
Prognosis
Protein Binding
RNA, Long Noncoding metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
RNA-Binding Proteins metabolism
Signal Transduction
Stomach Neoplasms metabolism
Stomach Neoplasms mortality
Stomach Neoplasms pathology
Survival Analysis
Transcription, Genetic
Adenocarcinoma genetics
Cyclin-Dependent Kinase Inhibitor p15 genetics
Cytoskeletal Proteins genetics
E2F1 Transcription Factor genetics
Gene Expression Regulation, Neoplastic
RNA, Long Noncoding genetics
RNA-Binding Proteins genetics
Stomach Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 28569791
- Full Text :
- https://doi.org/10.1038/cddis.2017.205