The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382

• Main Authors: Liang Zhao, Hongwei Sun, Hongru Kong, Zongjing Chen, Bicheng Chen, Mengtao Zhou
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-08-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Lncrna-TUG1; MiR-382; EZH2; Pancreatic cancer; Proliferation; Migration; EMT
• Online Access: http://www.karger.com/Article/FullText/479990
• ISSN: 1015-8987; 1421-9778

Background/Aims: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Methods: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT) phenotype. RNA-binding protein immunoprecipitation (RIP) and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2) was a target of miR-382 in PC. Results: In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Conclusion: Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous ‘sponge’ and competing for miR-382 binding to the miRNA target EZH2.