title: Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis.
abstract: The prognosis of gastric cancer (GC) patients with peritoneal dissemination remains poor, and a better understanding of the underlying mechanisms is critical for the development of new treatments that will improve survival in these patients. This study aimed to clarify the clinical and biological role of two key metastasis-associated long non-coding RNAs (lncRNAs) in GC. We analyzed the expression levels of two lncRNAs-Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX-Antisense Intergenic RNA (HOTAIR)-by real-time reverse transcription PCR in 300 gastric tissues (150 GC and 150 adjacent normal mucosa), and in seven GC cell lines. Functional characterization for the role of HOTAIR in GC was performed by small interfering RNA (siRNA) knockdown, followed by series of in-vitro and in-vivo experiments. Expression of both lncRNAs was significantly higher in cancerous tissues than in corresponding normal mucosa, and higher expression of these lncRNAs significantly correlated with peritoneal metastasis in GC patients. In addition, elevated HOTAIR expression emerged both as an independent prognostic and risk factor for peritoneal dissemination. SiRNA knockdown of HOTAIR in GC cells significantly inhibited cell proliferation, migration and invasion, but concurrently enhanced the anoikis rate in transfected cells. In an in vivo assay, HOTAIR siRNA-transfected MKN45 cells injected into nude mice inhibited the growth of xenograft tumors and peritoneal metastasis compared with controls. Our data provide novel evidence for the biological and clinical significance of HOTAIR expression as a potential biomarker for identifying patients with peritoneal metastasis, and as a novel therapeutic target in patients with gastric neoplasia.
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and.
authors.forename: Keun
authors.initials: K
authors.lastname: Hur
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Toden
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and.
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and ajay.goel@baylorhealth.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D023102:Anoikis; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: C561566:HOTAIR long untranslated RNA, human; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger