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

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. 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. 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. 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.

Zhao L ，Sun H ，Kong H ，Chen Z ，Chen B ，Zhou M ... -  《-》

TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p.

Cao J ，Han X ，Qi X ，Jin X ，Li X ... -  《-》

MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2.

Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD). However, chemoresistance remains a major impediment to clinical application of this agent. It has been presented that decreased miR-26a expression lead to cisplatin resistance and promoted growth and migration in human lung cancer. Enhancer of zeste homolog 2 (EZH2) is the target of miR-26a. The present study aimed to investigate the function of miR-26a/EZH2 in the acquisition of malignant behaviors of LAD. MiR-26a and EZH2 expression levels in the dcetaxel-insensitive groups (n = 19) and the docetaxel-sensitive groups (n = 18) were assessed by qRT-PCR. Colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays and western blotting were performed to assess the effects of miR-26a on proliferation, apoptosis and epithelial-to-mesenchymal (EMT) phenotypes in docetaxel resistant LAD cells in vitro. Xenograft transplantation, immunohistochemistry, tunel assays and western blotting assays were employed to demonstrate the role of miR-26a in docetaxel resistant LAD cells in vivo. The expression level of EZH2 in docetaxel-resistant LAD cells and corresponding parental cells was detected by qRT-PCR and western blotting. The relationship between miR-26a and EZH2 was confirmed by luciferase reporter assay. And rescue assays were performed to further confirm that miRNA-26a contributes to the acquisition of malignant behaviors of docetaxel-resistant LAD cells through targeting EZH2. MiR-26a was significantly down-regulated in the dcetaxel-insensitive groups (n = 19) compared with the docetaxel-sensitive groups (n = 18) assessed by qRT-PCR. MiR-26a decreased the proliferation, increased the apoptosis rate and reversed EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro. EZH2 was confirmed as target of miR-26a. Rescue assays further verified that the function of miR-26a exerts in docetaxel-resistant LAD cells is through targeting EZH2. Our data revealed that overexpression of miR-26a in docetaxel-resistant LAD cells could decrease the proliferation, increase the apoptosis rate and reverse EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro and such function is partially exerted via downregulating EZH2. MiR-26a/EZH2 signal pathway makes contribute to the malignant phenotype of docetaxel-resistant of LAD cells which indicated that miR-26a exerts pivotal functions in the molecular etiology of chemoresistant lung adenocarcinoma.

Chen J ，Xu Y ，Tao L ，Pan Y ，Zhang K ，Wang R ，Chen LB ，Chu X ... -  《-》

LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p.

Yan K ，Tian J ，Shi W ，Xia H ，Zhu Y ... -  《-》

lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1.

MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

He C ，Liu Z ，Jin L ，Zhang F ，Peng X ，Xiao Y ，Wang X ，Lyu Q ，Cai X ... -  《-》