title: A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer.
abstract: In more recent years, long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profile and functional role of lncRNAs in non-small cell lung cancer (NSCLC). In the present study, we determined the expression pattern of the growth arrest-specific transcript 5 (GAS5) in 72 NSCLC specimens by qRT-PCR and assess its biological functions in the development and progression of NSCLC. The results revealed that GAS5 expression was down-regulated in cancerous tissues compared to adjacent noncancerous tissues (P < 0.05) and was highly related to tumor size and TNM stage (P < 0.05). This correlation between GAS5 and clinicopathological parameters indicates that GAS5 might function as a tumor suppressor. Furthermore, GAS5 overexpression increased tumor cell growth arrest and induced apoptosis in vitro and in vivo. Meanwhile, siRNA-mediated knockdown of GAS5 promoted tumor cell growth. Importantly, through western blot analysis, we found that ectopic expression of GAS5 significantly up-regulated p53 expression and down-regulated transcription factor E2F1 expression. Taken together, these findings suggest that GAS5 is a tumor suppressor in NSCLC, and the action of GAS5 is mediated by p53-dependent and p53-independent pathways. GAS5 could serve as a potential diagnostic marker for NSCLC and may be a novel therapeutic target in patients with NSCLC.
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
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, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C561567:GAS5 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: GAS5; NSCLC; apoptosis; long non-coding RNAs; proliferation