title: Long noncoding RNA H19 is up-regulated in esophageal squamous cell carcinoma and promotes cell proliferation and metastasis.
abstract: Long noncoding RNAs (lncRNAs) have been shown to play various roles in tumorigenesis, among which lncRNA H19 has been revealed as an ambivalent factor that acts as both an oncogene and a tumor suppressor in carcinogenesis. However, the exact biological role of H19 in esophageal squamous cell carcinoma (ESCC) remains to be determined. The aim of this study was to examine the expression pattern of H19 in ESCC and evaluate its biological role and clinical significance in the progression of ESCC. Expression of H19 was analyzed in 64 ESCC tissues and four ESCC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Proliferation, cell cycle, migration, and invasion assays were performed in ESCC cell lines following knockdown of H19 to determine the biological function of H19 in the progression of ESCC both in vitro and in vivo. Western blot analysis was also performed to identify the potential mechanisms involved. H19 was highly expressed both in ESCC samples and cell lines compared with corresponding normal counterparts. The up-regulation of of H19 was significantly correlated with ESCC clinical stage and lymph node metastasis. Knockdown of H19 not only exerted inhibitory effect on tumor proliferation in vitro and in vivo, but also repressed the migratory and invasive capacity. G0/G1 phase arrest was also found in H19 knockdown cell lines. In addition, silencing of H19 up-regulated epithelial marker E-cadherin while down-regulating mesenchymal marker vimentin and metastasis-associated protein such as MMP-9. These findings indicate that H19 acts as an oncogene and promotes ESCC cell proliferation and metastasis, which may infer H19 as a marker of poor prognosis and, thus, a potential therapeutic target for treating ESCC patients.
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Chongqing, China.
authors.forename: Deli
authors.initials: D
authors.lastname: Tan
authors.affiliation: Department of Medical Genetics, College of Basic Medical Science, Third Military Medical University, Chongqing, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Chongqing, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Medical Genetics, College of Basic Medical Science, Third Military Medical University, Chongqing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Cardiothoracic Surgery, Southwest Hospital, Chongqing, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Yang
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D066298:In Vitro Techniques; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014746:Vimentin
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D014746:Vimentin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: H19; esophageal squamous cell carcinoma; long noncoding RNA; metastasis; proliferation