Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2
Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2
Abstract Background 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. Methods 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. Results 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. Conclusions Together, these results suggested that TUG1 mediates cell growth and chemoresistance of SCLC by regulating LIMK2b via EZH2.
- Southern Medical University China (People's Republic of)
- Hebei North University China (People's Republic of)
- Zhujiang Hospital China (People's Republic of)
Cancer Research, Lung Neoplasms, Antineoplastic Agents, Apoptosis, Kaplan-Meier Estimate, Cell Movement, Cell Line, Tumor, Humans, Enhancer of Zeste Homolog 2 Protein, Cell Proliferation, Neoplasm Staging, Research, Cell Cycle, Lim Kinases, Prognosis, Small Cell Lung Carcinoma, Gene Expression Regulation, Neoplastic, Oncology, Drug Resistance, Neoplasm, Gene Knockdown Techniques, Molecular Medicine, RNA, Long Noncoding, Protein Binding
Cancer Research, Lung Neoplasms, Antineoplastic Agents, Apoptosis, Kaplan-Meier Estimate, Cell Movement, Cell Line, Tumor, Humans, Enhancer of Zeste Homolog 2 Protein, Cell Proliferation, Neoplasm Staging, Research, Cell Cycle, Lim Kinases, Prognosis, Small Cell Lung Carcinoma, Gene Expression Regulation, Neoplastic, Oncology, Drug Resistance, Neoplasm, Gene Knockdown Techniques, Molecular Medicine, RNA, Long Noncoding, Protein Binding
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