Long noncoding RNA H19 indicates a poor prognosis of colorectal cancer and promotes tumor growth by recruiting and binding to eIF4A3
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Dong Han1,2,*, Xu Gao1,2,*, Meng Wang3,*, Yu Qiao1,2, Ya Xu1, Jing Yang1, Nazhen Dong1, Jun He1, Qian Sun1, Guixiang Lv1, Changqing Xu4, Ji Tao5, Ning Ma1,2
1Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China
2Heilongjiang Academy of Medical Sciences, Harbin, China
3Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
4Department of Pathophysiology, Harbin Medical University, Harbin, China
5Department of Gastrointestinal Medical Oncology, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
*These authors contributed equally to this work
Ning Ma, e-mail: [email protected]
Ji Tao, e-mail: [email protected]
Keywords: colorectal cancer, long noncoding RNA, H19, poor prognosis, cell proliferation
Received: December 14, 2015 Accepted: February 23, 2016 Published: March 14, 2016
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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