期刊
ONCOTARGET
卷 7, 期 16, 页码 22159-22173出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8063
关键词
colorectal cancer; long noncoding RNA; H19; poor prognosis; cell proliferation
资金
- Natural Science Foundation of China [81501998, 81270511, 81570534]
- Natural Science Foundation of Heilongjiang Province for youth [QC2013C089]
- Science and Technology Research Project of Education Department in Heilongjiang Province [12531226]
- Postdoctoral Foundation of Heilongjiang Province [LBH-TZ0415, LBH-Q15108, LBH-Q15079]
- Research Foundation for the Doctoral Program of Higher Education [20122307110002]
- Science and Technology Project of Heilongjiang Province [PS13S05]
- Harbin [2014RFXGJ053]
- Yu Weihan's academic funding for Distinguished Young Scholars of Harbin Medical University
The overall biological role and clinical significance of long non-coding RNA H19 in colorectal cancer (CRC) remain largely unknown. Here, we firstly report that the lncRNA H19 recruits eIF4A3 and promotes the CRC cell proliferation. We observed higher expression of H19 was significantly correlated with tumor differentiation and advanced TNM stage in a cohort of 83 CRC patients. Multivariate analyses revealed that expression of H19 served as an independent predictor for overall survival and disease-free survival. Further experiments revealed that overexpression of H19 promoted the proliferation of CRC cells, while depletion of H19 inhibited cell viability and induced growth arrest. Moreover, expression profile data showed that H19 upregulated a series of cell-cycle genes. Using bioinformatics prediction and RNA immunoprecipitation assays, we identified eIF4A3 as an RNA-binding protein that binds to H19. We confirmed that combining eIF4A3 with H19 obstructed the recruitment of eIF4A3 to the cell-cycle gene mRNA. Our results suggest that H19, as a growth regulator, could serve as a candidate prognostic biomarker and target for new therapies in human CRC.
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