Non-coding RNA Taurine Upregulated Gene 1 Research Articles

Long noncoding RNA TUG1 promotes cell proliferation and migration of renal cell carcinoma via regulation of YAP.

Recently, long noncoding RNAs (lncRNAs) have captured much attention for their important roles in human diseases. Deregulation of lncRNA taurine-upregulated gene 1 (TUG1) has been reported to regulate cancer progression in many cancer types. However, how TUG1 contributes to renal cell carcinoma (RCC) remains elusive; we were eager to resolve the questions. Tumor tissues and the matched adjacent normal tissues were collected from patients with RCC. Messenger RNA (mRNA) levels of TUG1, yes-associated protein (YAP), and microRNA (miR)-9 levels were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The regulation of YAP by TUG1 was investigated using Western blot analysis, RT-qPCR, and immunofluorescence. The oncogenic roles of TUG1 and YAP were studied using a cell proliferation assay and a wound healing assay. The interaction of TUG1-miR-9-YAP was analyzed in RCC cell lines. In the current study, we observed a positive correlation between TUG1 expression and YAP expression in RCC using the Gene Expression Omnibus database and tumor tissues collected from 58 patients with RCC. The TUG1 elevation enhanced YAP expression but did not alter the Hippo-signaling pathway activity or YAP protein distribution in cells. In addition, we found that TUG1 could bind to miR-9; therefore, TUG1 could positively control YAP expression via downregulation of miR-9 level. Furthermore, we observed that inhibition of cell proliferation and cell migration induced by TUG1 silencing could be reversed by overexpression of YAP in RCC cell lines. Our findings indicated a pivotal role of TUG1 in driving RCC progression via regulation of miR-9/YAP, suggesting a potential therapeutic targeting role of TUG1 in RCC.

Long non-coding RNA TUG1 promotes the proliferation of colorectal cancer cells through regulating Wnt/β-catenin pathway.

The long non-coding RNA taurine up-regulated gene 1 (TUG1) has been shown to be dysregulated in various types of malignant cancer; however, its underlying mechanism of action has not been fully elucidated. The present study aimed to investigate the biological role and clinical significance of TUG1 in the progression of colorectal cancer (CRC). A reverse transcription-quantitative polymerase chain reaction assay was used to evaluate TUG1 expression in tissues from patients with CRC. The effect of TUG1 on cell viability of CRC cells using MTT assay. The influence of TUG1 on tumorigenesis was monitored using an in vivo xenograft model. The status of the Wnt/β-catenin signaling pathway was evaluated using immunofluorescence, western blotting and luciferase reporter assays. The results demonstrated that the expression of TUG1 was positively associated with the pathological grade and clinical stage of CRC patients. Knockdown of TUG1 inhibited the proliferation of CRC cells and attenuated the activity of Wnt/β-catenin pathway in CRC cells. In addition, TUG1 knockdown inhibited the tumorigenicity in the in vivo CRC xenograft model, as well as the nuclear localization of β-catenin and downstream gene transcription. Taken together, the data of the present study highlighted the pivotal role of the TUG1-Wnt/β-catenin signaling pathway in CRC, which could be targeted to improve the therapeutic efficacy of CRC.

LncRNA TUG1 affects cell viability by regulating glycolysis in osteosarcoma cells

Osteosarcoma is an aggressive malignant neoplasm in teenagers and young adults. Long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is considered as an oncogene in osteosarcoma. However, the mechanism of TUG1 in regulating osteosarcoma has not been fully understood. We aimed to investigate whether the metabolic alteration is involved in the effect of TUG1 on osteosarcoma cells. Herein, we found that TUG1 was overexpressed in osteosarcoma cells compared with the normal osteoblastic cell line. Knockdown of TUG1 inhibited glucose consumption, lactate production and cell viability of osteosarcoma cells. Overexpression of TUG1 induced cell viability, whereas the induction was attenuated by 2-DG. The aberrant expression of TUG1 markedly affected the expression of hexokinase-2 (HK2). Knockdown of HK2 weakened the effect of TUG1 overexpression on glycolysis in osteosarcoma cells. We concluded that glycolysis was involved in the effect of TUG1 on cell viability of osteosarcoma cells. HK2 might be an important molecule by which TUG1 affected the glycolysis.

Knockdown of Long Noncoding RNA TUG1 Inhibits the Proliferation and Cellular Invasion of Osteosarcoma Cells by Sponging miR-153.

Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been confirmed to be involved in the progression of various cancers; however, its mechanism of action in osteosarcoma has not been well addressed. In our study, TUG1 was overexpressed and miR-153 was downregulated in osteosarcoma tissues and cell lines. A loss-of-function assay showed that TUG1 knockdown suppressed the viability, colony formation, and invasion of osteosarcoma cells in vitro. Moreover, TUG1 was confirmed to be an miR-153 sponge. Ectopic expression of TUG1 reversed the inhibitory effect of miR-153 on the proliferation and invasion of osteosarcoma cells. Further transplantation experiments proved the carcinogenesis of TUG1 in osteosarcoma in vivo. Collectively, our study elucidated that TUG1 contributes to the development of osteosarcoma by sponging miR-153. These findings may provide a novel lncRNA-targeted therapy for patients with osteosarcoma.

Long non-coding RNA TUG1 promotes osteosarcoma cell proliferation and invasion through inhibition of microRNA-212-3p expression.

Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), has recently been suggested to be associated with the development of osteosarcoma (OS), but the underlying molecular mechanism still remains largely unclear. In the present study, it was revealed that TUG1 was significantly upregulated whereas miR-212-3p was significantly downregulated in OS tissues and cell lines, when compared with adjacent non-tumor tissues and normal osteoblasts cell lines, respectively. An inverse association between the TUG1 and miR-212-3p expression was also observed in OS tissues. Furthermore, TUG1 directly interacted with miR-212-3p and negatively regulated the expression of miR-212-3p in OS cells. In vitro experiments further indicated that inhibition of TUG1 suppressed the proliferation and invasion of OS cells. Furthermore, knockdown of miR-212-3p eliminated the suppressive effects of TUG1 inhibition on the proliferation and invasion of OS cells. Taken together, these findings demonstrate that TUG1 promotes OS cell proliferation and invasion by inhibition of miR-212-3p expression, thus suggesting that TUG1 may become a potential therapeutic target for OS.

Long non-coding RNA taurine-upregulated gene 1 predicts unfavorable prognosis, promotes cells proliferation, and inhibits cells apoptosis in epithelial ovarian cancer.

The aim of this study was to evaluate the correlation of long non-coding RNAs (lncRNAs) taurine-upregulated gene 1 (TUG1) with clinicopathological characteristics as well as overall survival (OS) in epithelial ovarian cancer (EOC) patients, and investigate its function in EOC cells proliferation and apoptosis in vitro.LncRNA TUG1 expressions were detected in tumor tissues and paired adjacent tissues obtained from 96 EOC patients. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor plasmids were transfected into SKOV3 cells. CKK-8, annexin V-FITC–propidium iodide, qPCR and western blot assays were performed to detect cells proliferation, cells apoptosis, RNA expression, and protein expression, respectively.LncRNA TUG1 expression was higher in tumor tissue compared to paired adjacent tissue (P < .001), and it was positively correlated with pathological grade (P = .022), tumor size (P = .011) and FIGO stage (P < .001). Kaplan-Meier curve showed that lncRNA TUG1 high expression was associated with worse OS (P = .003). Multivariate Cox analysis indicated that lncRNA TUG1 high expression (vs. low expression) (P = .035) was independently predictive factor for shorter OS. In vitro, cells proliferation was promoted after treatment with lncRNA TUG1 mimic and was suppressed after treatment with lncRNA TUG1 inhibitor. In addition, cells apoptosis rate was decreased in lncRNA TUG1 mimic group compared to NC1 mimic, and increased in lncRNA TUG1 inhibitor group compared to NC2 inhibitor.In conclusion, lncRNA TUG1 is positively correlated with advanced disease and poor prognosis, and it promotes cells proliferation and inhibits cells apoptosis in EOC cells.

Long non-coding RNA taurine-upregulated gene 1 correlates with poor prognosis, induces cell proliferation, and represses cell apoptosis via targeting aurora kinase A in adult acute myeloid leukemia.

This study aimed to investigate the correlation of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) with clinicopathological feature and prognosis, and to explore its effect on cell proliferation and apoptosis as well as the relevant target genes in adult acute myeloid leukemia (AML). LncRNA TUG1 expression was detected in bone marrow samples from 186 AML patients and 62 controls. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor lentivirus vectors were transfected in KG-1 cells. Rescue experiment was performed by transfection of lncRNA TUG1 inhibitor and aurora kinase A (AURKA) mimic lentivirus vectors. Cell proliferation, apoptosis, RNA, and protein expressions were determined by CKK-8, annexin V-FITC-propidium iodide, quantitative polymerase chain reaction, and western blot assays. LncRNA TUG1 expression was higher in AML patients compared to controls and correlated with higher white blood cell counts, monosomal karyotype, FLT3-ITD mutation, poor-risk stratification, and poor prognosis, which independently predicted worse event-free survival and overall survival. In vitro, lncRNA TUG1 expression was higher in AML cell lines (KG-1, MOLM-14, HL-60, NB-4, and THP-1 cells) compared to controls. LncRNA TUG1 mimic promoted cell proliferation and decreased cell apoptosis rate, while lncRNA TUG1 inhibitor repressed cell proliferation and increased cell apoptosis rate. Rescue experiment showed that AURKA attenuated the influence of lncRNA TUG1 on AML cell proliferation and apoptosis. In conclusion, lncRNA TUG1 associates with advanced disease and worse prognosis in adult AML patients, and it induces AML cell proliferation and represses cell apoptosis via targeting AURKA.

Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma.

BackgroundMalignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers. The function of lncRNA TUG1 on growth of melanoma was investigated in this study.Material/MethodsThe TUG1 and miR-129-5p expression were examined via qRT-PCR. The protein expression was investigated by Western blotting assay. Luciferase reporter assay was used to assess if lncRNA TUG1 can bind to miR-129-5p and if miR-129-5p can target AEG1 mRNA. CCK-8 and apoptosis assay were used to detect cell growth and apoptosis. The metastasis of melanoma cells was detected by wound-healing and Transwell assays. The effects of TUG1 on growth of melanoma in vivo and cell chemoresistance were investigated via xenograft animal experiment and CCK-8 assay.ResultsThe expression of TUG1 and AEG1 was elevated and the miR-129-5p level was decreased in melanoma specimens and cell lines. Downregulation of either TUG1 or AEG1 suppressed cell growth and metastasis. miR-129-5p can bind directly to AEG1 and TUG1 can directly sponge miR-129-5p. Inhibition of TUG1 expression suppressed the expression of Bcl-2, MMP-9, and cyclin D1, and raised the level of cleaved caspase3 by modulating AEG1 level in melanoma cells. Inhibition of TUG1 reduced the growth of tumors in vivo and improved the chemosensitivity of A375 cells to cisplatin and 5-FU.ConclusionsReduction of TUG1 level suppressed cell growth and metastasis by regulating AEG1 expression mediated by targeting miR-129-5p. Suppression of lnc TUG1 may be a promising therapeutic strategy in the treatment of malignant melanoma.

Downregulation of the long non-coding RNA taurine-upregulated gene 1 inhibits glioma cell proliferation and invasion and promotes apoptosis.

Expression of the long non-coding RNA taurine-upregulated gene 1 (TUG1) is associated with various aggressive tumors. The present study aimed to investigate the biological function of TUG1 in regulating apoptosis, proliferation, invasion and cell cycle distribution in human glioma U251 cells. Lentivirus-mediated TUG1-specific microRNA was transfected into U251 cells to abrogate the expression of TUG1. Flow cytometry analysis was used to examine the cell cycle distribution and apoptosis of U251 cells. Cellular proliferation was examined using Cell Counting Kit-8 (CCK-8) assays and invasion was examined by Transwell assays. The apoptotic rate of cells in the TUG1-knockdown group was significantly higher than in the negative control (NC) group (11.58 vs. 9.14%, P<0.01). CCK-8 assay data demonstrated that the proliferative ability of cells within the TUG1-knockdown group was lower compared with that of the NC group. A Transwell invasion assay was performed, which revealed that the number of invaded cells from the TUG1-knockdown group was the less compared with that of the NC group. In addition, the G0/G1 phase population was significantly increased within the treated group (44.85 vs. 38.45%, P<0.01), as measured by flow cytometry. The present study demonstrated that the downregulation of TUG1 may inhibit proliferation and invasion, and promote glioma U251 cell apoptosis. In addition, knockdown of TUG1 may have an effect on cell cycle arrest. The data presented in the current study indicated that TUG1 may be a novel therapeutic target for glioma.

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

Background/Aims: 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). Methods: 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. Results: 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. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

The Long Noncoding RNA TUG1 Promotes Laryngeal Cancer Proliferation and Migration

Background/Aims: Researchers have shown that long noncoding RNAs are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). However, the role of the long noncoding RNA taurine-upregulated gene 1 (TUG1) in the pathogenesis of LSCC remains unclear, although it is recognized as an oncogenic regulator for several types of squamous cell carcinoma. Methods: qRT-PCR was performed to measure the expression of TUG1 in LSCC tissues and cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to measure the effect of TUG1 on cell proliferation. Transwell assay and flow cytometry were employed to determine the effect of TUG1 on cell migration and invasion. Western-blot were performed to explore the relation of TUG1 and p53 mRNA. Results: Higher TUG1 expression in LSCC than in paired normal tumor-adjacent tissue specimens (N = 64) was observed using quantitative real-time polymerase chain reaction. Also, high TUG1 expression was positively associated with advanced T category, worse lymph node metastasis and late clinical stage. Furthermore, in vitro experiments demonstrated that silencing of TUG1 markedly inhibited proliferation, cell-cycle progression, migration, and invasion of LSCC cells, whereas depletion of TUG1 led to increased apoptosis. Conclusion: These findings demonstrated that upregulated TUG1 expression exerted oncogenic effects by promoting proliferation, migration, and invasion, and inhibiting apoptosis in LSCC cells.

Downregulation of the long non-coding RNA TUG1 is associated with cell proliferation, migration, and invasion in breast cancer

Recent studies have identified many long non-coding RNAs (lncRNAs) with critical roles in various biological processes including tumorigenesis. Taurine-upregulated gene 1 (TUG1), is an lncRNA recently reported to be involved in the progression of several human cancers. This study aimed to investigate the clinical significance and biological functions of TUG1 in breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure TUG1 expression in cells from breast cancer cell lines and in 58 matched pairs of breast cancer and normal tissue samples from patients with clinicopathological comparisons. Gain-and loss-of-function experiments were performed in vitro to investigate the biological role of TUG1. TUG1 expression was significantly downregulated in both breast cancer tissues and cell lines compared to controls, and low TUG1 expression was significantly correlated with mutant p53 expression (p=0.037) and lymph node metastasis (p=0.044). In vitro experiments revealed that TUG1 overexpression significantly suppressed cell proliferation by causing cell cycle arrest and inducing apoptosis in breast cancer cells, while TUG1 knockdown caused increased cell growth via promoting cell cycle progression and regulating the expression of cyclinD1 and CDK4. Further functional assays indicated that TUG1 overexpression significantly promoted cell migration and invasion while TUG1 knockdown had the opposite effects. Our findings indicate that the lncRNA TUG1 is a tumor suppressor in breast cancer, and may serve as a novel prognostic biomarker and potential therapeutic target for patients with breast cancer.

Prognostic value of long non-coding RNA TUG1 in various tumors.

Taurine up-regulated gene 1 (TUG1) is a long non-coding RNA (lncRNA), has been reported that be dysregulated in various tumors, involved in proliferation and apoptosis in a variety of tumor cells. To detect the clinical significance of TUG1 expression in tumor patients, we carried out current systematic review and meta-analysis investigating its relation with the prognosis and clinicopathological features of cancers. A total of 15 studies comprise 1560 patients were analyzed. The pooled results showed that no significant relationship between high TUG1 expression and overall survival (OS) (HR = 1.28, 95% CI: 0.96–1.69, P = 0.091) in various tumors. In the subgroup analysis by cancer type, elevated TUG1 expression was associated with poorer survival in cancer patients with high TUG1 expression subgroup but better survival in patients with low TUG1 expression subgroup. Over-expression of TUG1 associated with significantly unfavorable survival for bladder cancer (HR=2.67, 95% CI: 1.47–4.87, P = 0.001). Up-regulation of TUG1 correlated with distant metastasis (DM) (OR = 4.22, 95% CI: 2.66–6.70, P < 0.001) and tumor differentiation (OR = 2.45, 95% CI: 1.28–4.70, P = 0.007), but failed to show inline to gender (OR = 1.04, 95% CI: 0.77–1.42, P = 0.774), age (OR = 0.75, 95% CI: 0.51–1.10, P = 0.136), lymph node metastasis (LNM) (OR = 1.45, 95% CI: 0.85–2.50, P = 0.177), and TNM stage (OR = 0.55, 95% CI: 0.17–1.81, P = 0.326). The overall results suggest lncRNA TUG1 may be a useful prognostic biomarker in cancer patients.

The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pattern of TUG1 and evaluate its clinical significance as well as prognostic potential in CCA. In addition, the functional roles of TUG1 including cell proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover, overexpression of TUG1 is linked to tumor size (p=0.005), TNM stage (p=0.013), postoperative recurrence (p=0.036) and overall survival (p=0.010) of CCA patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression inhibited metastasis potential in vitro by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target.

An invitro study of the long non-coding RNA TUG1 in tongue squamous cell carcinoma.

This study sought to study the expression of the long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) in tongue squamous cell carcinoma (TSCC) and reveal its possible function. qRT-PCR was used to evaluate 27 samples of fresh TSCC tissues and adjacent normal tongue tissues. siRNA technology was employed to downregulate TUG1 expression in CAL-27 and SCC-9 cell lines. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was utilized to assess cell proliferation ability; apoptosis and cell-cycle phases were analysed via flow cytometry. qRT-PCR findings indicated that the lncRNA TUG1 was upregulated in TSCC tissues compared with adjacent normal tongue tissues (P<.05). After TUG1 expression was downregulated using siRNA technology, cell proliferation was significantly inhibited (P<.05), and the number of cells in S phase was reduced (P<.05). The lncRNA TUG1 may represent a potential oncogene in TSCC.

Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: a meta-analysis.

LncRNA taurine upregulated gene 1 (TUG1) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the usefulness of TUG1 as a prognostic marker in malignant tumors. The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to Jan 11, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between TUG1 expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between TUG1 expression and pathological parameters. Thirteen original studies covering 1,274 cancer patients were included in this meta-analysis. The pooled HR suggested that high TUG1 expression correlated with poor OS (pooled HR=1.41, 95% CI: 1.01-1.98) in cancer types other than non-small cell lung cancer. TUG1 expression was also related to distant metastasis (OR=3.24, 95% CI: 1.18-8.93), large tumor size (OR=4.07, 95% CI: 1.08-15.28) and advanced tumor stage (OR=3.45, 95% CI: 2.19-5.44). Begg’s funnel plot and Egger’s test showed no evidence of obvious asymmetry for overall survival or tumor stage. Thus high TUG1 expression appears predictive of poor OS, distant metastasis, advanced tumor stage and large tumor size. This suggests TUG1 expression could serve as a biomarker for poor prognosis in cancers.

Long Noncoding RNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation and Invasion in Gastric Cancer via Negatively Modulating miRNA-145-5p.

Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is involved in the development and carcinogenesis of various tumors, suggesting the diagnostic potential of TUG1 in these cancers. However, the exact role of TUG1 and its underlying mechanism in gastric cancer (GC) remain unknown. In this study, the expression of TUG1 and miR-145-5p in GC cell lines and nonmalignant gastric epithelial cell lines was detected by qRT-PCR. BGC-823 and SGC-7901 cells were transfected with si-TUG1, pcDNA 3.1-TUG1, miR-145-5p mimics, or matched controls. The biological function of TUG1 and miR-145-5p in GC cell proliferation and invasion in vitro and tumor growth in vivo was investigated by MTT assay, Transwell invasion assay, and tumor xenograft experiments. The regulating relationship between TUG1 and miR-145-5 was confirmed by luciferase reporter assay. The results showed that TUG1 was significantly overexpressed and miR-145-5p was dramatically downregulated in GC cell lines. TUG1 knockdown strikingly inhibited cell proliferation and invasion in vitro and markedly suppressed tumor growth in vivo. Furthermore, TUG1 could directly bind to miR-145-5p and repress miR-145-5p expression. TUG1 overexpression significantly relieved the inhibition on GC cell proliferation and invasion in vitro and tumor growth in vivo, mediated by miR-145-5p overexpression. In conclusion, TUG1 promotes cell proliferation and invasion in GC via negatively modulating miRNA-145-5p, which undoubtedly contributes to understanding the mechanism of GC occurrence and development.

Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells

BackgroundBladder cancer is a common serious disease around the world. Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the development and progression of various cancers, including bladder cancer. The aim of this study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1) on proliferation and apoptosis in bladder cancer cell lines and the underlying mechanism.MethodsThe levels of TUG1 were detected by quantitative real time polymerase chain reaction (qRT-PCR) in bladder cancer tissues and cells. The mRNA and protein levels of zinc finger E-box binding homeobox 2 (ZEB2) were measured by qRT-PCR and Western blot analysis, respectively. The functional targets of TUG1 were predicted by online softwares and confirmed by luciferase reporter assay. The effects of TUG1 on cell proliferation and apoptosis were examined by MTT and apoptosis assay, respectively. The expression levels of β-catenin, cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis.ResultsThe levels of TUG1 and ZEB2 were significantly increased in bladder cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2 overexpression reversed the effects of TUG1 knockdown on cell proliferation and apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142 could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the Wnt/β-catenin pathway by regulating ZEB2 expression in bladder cancer cells.ConclusionDownregulation of TUG1 expression inhibited proliferation and induced apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through the inactivation of Wnt/β-catenin pathway.

Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells.

Long non‐coding RNA (lncRNA) have been the focus of increasing attention due to the role they play in many diseases, including osteosarcoma. The function of taurine upregulated gene 1 (TUG1) and its mechanism in osteosarcoma remain unclear. In our research, we found that TUG1 was elevated and correlated with a poor prognosis in osteosarcoma patients. In addition, the following functional experiment showed that decreased TUG1 could remarkably inhibit osteosarcoma cell migration and invasion, indicating that TUG1 functioned as an oncogene in osteosarcoma. Moreover, we revealed that TUG1 and Rho‐associated coiled‐coil‐containing protein kinase 1 (ROCK1), a metastasis‐related gene targeted by microRNA‐335‐5p (miR‐335‐5p), had the same miR‐335‐5p combining site. The subsequent luciferase assay verified TUG1 was a target of miR‐335‐5p. Furthermore, the results of a real‐time quantitative PCR showed that TUG1 and miR‐335‐5p could affect each other's expression. respectively. Finally, we affirmed that TUG1 affected ROCK1 expression and ROCK1‐mediated migration/invasion by working as a competitive endogenous RNA (ceRNA) via miR‐335‐5p. In summary, the findings of this study, based on ceRNA theory, combining the research foundation of miR‐335‐5p and ROCK1, and taking TUG1 as a new study point, provide new insight into molecular‐level reversing migration and invasion of osteosarcoma.

Long Non-Coding RNA TUG1 Promotes Proliferation and Inhibits Apoptosis of Osteosarcoma Cells by Sponging miR-132-3p and Upregulating SOX4 Expression

PurposeLong non-coding RNA taurine upregulated gene 1 (TUG1) is reported to be a vital regulator of the progression of various cancers. This study aimed to explore the exact roles and molecular mechanisms of TUG1 in osteosarcoma (OS) development.Materials and MethodsReal-time quantitative PCR was applied to detect the expressions of TUG1 and microRNA-132-3p (miR-132-3p) in OS tissues and cells. Western blot was performed to measure protein levels of sex determining region Y-box 4 (SOX4). Cell viability was assessed using XTT assay. Cell apoptosis was evaluated using flow cytometry and caspase-3 activity detection assays. Bioinformatics analysis and luciferase reporter experiments were employed to confirm relationships among TUG1, miR-132-3p, and SOX4.ResultsTUG1 was highly expressed in human OS tissues, OS cell lines, and primary OS cells. TUG1 knockdown hindered proliferation and induced apoptosis in human OS cell lines and primary OS cells. Moreover, TUG1 inhibited miR-132-3p expression by direct interaction, and introduction of miR-132-3p inhibitor partly abrogated the effect of TUG1 knockdown on the proliferation and apoptosis of OS cells. Furthermore, SOX4 was validated as a target of miR-132-3p. Further functional analyses revealed that miR-132-3p inhibited proliferation and induced apoptosis of OS cells, while this effect was greatly abated following SOX4 overexpression. Moreover, TUG1 knockdown suppressed proliferation and promoted apoptosis by upregulating miR-132-3p and downregulating SOX4 in primary OS cells.ConclusionTUG1 facilitated proliferation and suppressed apoptosis by regulating the miR-132-3p/SOX4 axis in human OS cell lines and primary OS cells. This finding provides a potential target for OS therapy.