title: Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer.
abstract: Long noncoding RNA (lncRNA) plays pivotal roles in cancer development. To date, only a small number of lncRNAs have been characterized at functional level. Here, we discovered a novel lncRNA termed GAS5-AS1 as a tumor suppressor in non-small cell lung cancer (NSCLC). The expression of GAS5-AS1 in NSCLC tumors was much lower than that in the adjacent normal lung tissues. The reduced GAS5-AS1 was significantly correlated with larger tumors, higher TNM stages, and lymph node metastasis in NSCLC patients. While ectopic expression or specific knockdown of GAS5-AS1 had no effect on proliferation, cell cycle progression, and apoptosis, it dramatically decreased or increased, respectively, NSCLC cell migration and invasion. Overexpression of GAS5-AS1 in NSCLC cells reduced a cohort of molecules (ZEB1, N-cadherin, Vimentin, and/or Snail1) critical for epithelial-mesenchymal transition (EMT). Furthermore, the DNA demethylating agent 5-aza-2-deoxycytidine failed to upregulate GAS5-AS1 in NSCLC cells, whereas the pan-HDAC inhibitors panobinostat and SAHA significantly induced GAS5-AS1 in a dose-dependent manner. In addition, GAS5-AS1 can be upregulated by specific knockdown of HDAC1 or HDAC3. Collectively, our data suggest that histone modifications play a major role leading to epigenetic silencing of GAS5-AS1 in NSCLC and subsequently promote tumor metastasis via upregulation of several key EMT markers.
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.|Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Lyu
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Huzhou Central Hospital, Huzhou, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Bolin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D042421:Histone Code / Q000187:drug effects / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism
chemical_list: C561567:GAS5 long non-coding RNA, human; D056572:Histone Deacetylase Inhibitors; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm