title: Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2.
abstract: Taurine upregulated gene1 (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. However, the biological functions of lncRNA TUG1 in small cell lung cancer (SCLC) remain unknown. The aim of this study is to explore the roles of TUG1 in cell growth and chemoresistance of SCLC and its possible molecular mechanism.
  
  
  
  The expression of TUG1 in thirty-three cases of SCLC tissues and SCLC cell line were examined by quantitative RT-PCR (qRT-PCR). The functional roles of TUG1 in SCLC were demonstrated by CCK8 assay, colony formation assay, wound healing assay and transwell assay, flow cytometry analysis and in vivo study through siRNA or shRNA mediated knockdown. Western blot assays were used to evaluate gene and protein expression in cell lines. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) were performed to confirm the molecular mechanism of TUG1 involved in cell growth and chemoresistance of small cell lung cancer.
  
  
  
  We found that TUG1 was overexpressed in SCLC tissues, and its expression was correlated with the clinical stage and the shorter survival time of SCLC patients. Moreover, downregulation of TUG1 expression could impair cell proliferation and increased cell sensitivity to anticancer drugs both in vitro and in vivo. We also discovered that TUG1 knockdown significantly promoted cell apoptosis and cell cycle arrest, and inhibited cell migration and invasion in vitro . We further demonstrated that TUG1 can regulate the expression of LIMK2b (a splice variant of LIM-kinase 2) via binding with enhancer of zeste homolog 2 (EZH2), and then promoted cell growth and chemoresistance of SCLC.
  
  
  
  Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.
authors.affiliation: Department of Pathology Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, People's Republic of China.|Department of Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Pathology Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, People's Republic of China.
authors.forename: Weimei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pathology Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, People's Republic of China.
authors.forename: Shun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Pathology Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Pathology Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, People's Republic of China. linlangg@yahoo.com.
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D054461:Lim Kinases / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D062085:RNA, Long Noncoding; C000598536:TUG1 long noncoding RNA, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C102895:LIMK2 protein, human; D054461:Lim Kinases
keywords: Cell growth; Chemoresistance; Small cell lung cancer (SCLC); TUG1