title: LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer.
abstract: lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Y-w
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: E-b
authors.initials: EB
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: X-h
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Z-h
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: T-p
authors.initials: TP
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: W
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Oncology, Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, PR China.
authors.forename: B-r
authors.initials: BR
authors.lastname: Liu
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Z-x
authors.initials: ZX
authors.lastname: Wang
mesh_terms: D000818:Animals; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006657:Histones / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009363:Neoplasm Proteins; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C561566:HOTAIR long untranslated RNA, human; D006657:Histones; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C430461:SUZ12 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2