title: Long noncoding RNA H19 indicates a poor prognosis of colorectal cancer and promotes tumor growth by recruiting and binding to eIF4A3.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Nazhen
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.|Heilongjiang Academy of Medical Sciences, Harbin, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D018572:Disease-Free Survival; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000378:metabolism*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D039601:Eukaryotic Initiation Factor-4A; C403493:EIF4A3 protein, human; D053487:DEAD-box RNA Helicases
keywords: H19; cell proliferation; colorectal cancer; long noncoding RNA; poor prognosis