Effects of Long Noncoding RNA TUG1 (Taurine Up-Regulated Gene 1) on Growth and Metastasis of the Non-Small Cell Lung Cancer and Its Mechanism

Objective: Our research was to discuss effects and mechanism of lncRNA TUG1 in NSCLC by vitro study. Methods: A549 and H1299 cells were divided into NC, pcDNA 3.1 and lncRNA TUG1 groups. Measuring cell proliferation using CCK-8 assay, cell apoptosis by flow cytometry, invasion cell number by transwell and wound healing rate by wound healing assay. Relative gene and protein expressions by RT-qPCR and WB assay. Results: Compared with NC group, the cell proliferation rate, invasion cell number and wound healing rate were significantly depressed in A549 and H1299 cell lines (P < 0.001, respectively). By RT-qPCR and WB assay, lncRNA TUG1 gene expression were significantly increased (P < 0.001, respectively); E-cadherin gene and protein expression were significantly up-regulation, and N-cadherin and Vimentin gene and protein expressions were significantly depressed compared with those of NC group in A549 and H1299 cell lines (P < 0.001, respectively). Conclusion: lncRNA TUG1 had effects to suppress NSCLC cell biological activities by regulation EMT relative gene and proteins expression in vivo study.

lncRNA TUG1 Facilitates Colorectal Cancer Stem Cell Characteristics and Chemoresistance by Enhancing GATA6 Protein Stability

Background. Chemoresistance and tumor recurrence lead to high deaths in colorectal cancer (CRC) patients. Cancer stem cells (CSCs) contribute to these pathologic properties, but the exact mechanisms are still poorly understood. This study identified that long noncoding RNA (lncRNA) TUG1 was highly expressed in CRC stem cells and investigated its mechanism. Methods. After the CD133+/CD44+ cells with cancer stem cell (CSC) characteristics were isolated and identified by flow cytometry, lncRNA TUG1 expression was quantified by quantitative real-time PCR. The lncRNA TUG1 function was further investigated using gain- and loss-of-function assays, sphere formation, Western blot, Cell Counting Kit-8 assay, and cell apoptosis detection. Moreover, the mechanism was explored by RNA pull-down assay, RNA immunoprecipitation, and cycloheximide- (CHX-) chase assays. Results. lncRNA TUG1 was elevated in CD133+/CD44+ cells with CSC characteristics. Functionally, lncRNA TUG1 increased the characteristics and oxaliplatin resistance of CRC stem cells. Mechanically, lncRNA TUG1 interacted with GATA6 and positively regulated its protein level and the rescue assays corroborated that lncRNA TUG1 knockdown repressed the characteristics and oxaliplatin resistance of CRC stem cells by decreasing GATA6 and functioned in CRC by targeting the GATA6-BMP signaling pathway. Furthermore, the in vivo assay verified the lncRNA TUG1 function in facilitating the characteristics and oxaliplatin resistance of CRC stem cells. Conclusion. lncRNA TUG1 facilitated CRC stem cell characteristics and chemoresistance by enhancing GATA6 protein stability.

LncRNA TUG1 facilitates the development of endometrial cancer via interaction with FXR1

Purpose: To investigate the potential influence of long non-coding RNA (lncRNA) TUG1 on the development of endometrial cancer (EC).Methods: A total of 24 paired EC species and paracancerous species were collected, and the differential expressions of TUG1 in them were determined. The regulatory effects of TUG1 on proliferative and migratory potential in Ishikawa and HEC-1A cells were assessed using cell counting kit-8 (CCK-8) and Transwell assay, respectively. Potential protein binding TUG1 was predicted by bioinformatics analysis and subsequently verified using RIP (RNA-Binding Protein Immunoprecipitation) assay. Rescue experiments were conducted to uncover the mechanism of TUG1 in regulating the development of EC.Results: TUG1 was highly expressed in EC species and cell lines. Higher levels of TUG1 was observed in EC patients with metastases than those without metastatic cancer (p < 0.05). Overexpression of TUG1 markedly facilitated proliferative and migratory potential in EC cells. Taurine-upregulated gene 1 (TUG1) directly bound Fragile X-related protein 1 (FXR1) and positively regulated its level (p < 0.05). Through interaction with FXR1, TUG1 stimulated the malignant development of EC.Conclusion: LncRNA TUG1 is upregulated in EC species, which facilitates proliferative and migratory potentials in EC cells by interacting with FXR1.

Study of lncRNA TUG1/miR-320 in EPC Transplantation to Improve Lower Limb Ischemia and Promote Angiogenesis in Mice

To The aim of the current study was to investigate the changes in lncRNA TUG1/miR-320 and related proteins with ischaemic time in an ischemia model. A nude mouse model of lower limb ischemia was established by ligating the femoral artery, and laser Doppler measurements were used to demonstrate the successful establishment of the ischemia model. The cells were extracted from the bone marrow of nude mice, and the proliferation, migration and vascular-forming ability of the cells were analysed. When transplanted into ischemia model mice, blood flow measurements indicated that EPCs can speed up blood flow recovery. The results of HE staining indicated an improvement in inflammatory damage, and immunohistochemistry revealed an increase in capillaries. RT-PCR and Western blot experiments showed that the improvement of ischemia was related to an increase in lncRNA TUG1 and a decrease in miR-320 and that the expression of the related downstream proteins STAT3, VEGFR-2, Wnt-5a and β-catenin increased gradually. These changes promoted an increase in capillaries, the recovery of blood flow, and the improvement of muscle damage. Therefore, EPC transplantation can improve the inflammatory response of lower limb muscles by increasing the expression of lncRNA TUG1 and thereby accelerate the recovery of ischaemic limbs.