Abstract
BackgroundTaurine 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.MethodsThe 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.ResultsWe 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.ConclusionsTogether, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.
Highlights
Taurine upregulated gene1 (TUG1) as a 7.1-kb long non-coding RNAs (lncRNAs), has been shown to play an oncogenic role in various cancers
The expression of TUG1 increased in small cell lung cancer (SCLC) tissues and was associated with clinical stage and survival To investigate the clinicopathological features of TUG1 expression in SCLC, quantitative RT-PCR (qRT-PCR) was performed in 33 tumor samples from SCLC patients
The data indicated that higher expression of TUG1 in extensive disease-SCLC (ED-SCLC) than in limited disease SCLC (LD-SCLC) (P = 0.011)
Summary
Taurine upregulated gene (TUG1) as a 7.1-kb lncRNA, has been shown to play an oncogenic role in various cancers. 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. Though genetic changes have been reported in SCLC [6], the precise molecular mechanisms involved in SCLC development and chemoresistance remain to be fully elucidated. Increasing evidence suggests that lncRNAs play a important role in tumorigenesis, and their aberrant expression confers tumor initiation, cancer cell growth and apoptosis, chemoresistance, invasion and metastasis [12,13,14]. Studies showed that the long non-coding RNA HOTTIP promotes gemcitabine resistance by regulating HOXA13 in pancreatic cancer [14]. Functional roles of lncRNAs in SCLC have not been well documented
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