Taurine-upregulated Gene 1 Silencing Research Articles

Knockdown of long non-coding RNA TUG1 depresses apoptosis of hippocampal neurons in Alzheimer's disease by elevating microRNA-15a and repressing ROCK1 expression.

Many studies have already suggested the role of long non-coding RNAs (lncRNAs) in Alzheimer's disease (AD), but the functions of lncRNA Taurine Upregulated Gene 1 (TUG1) in AD have been scarcely discussed. This study aims to verify how TUG1 affects hippocampal neurons in AD through modulation of microRNA-15a (miR-15a)/Rho-associated protein kinase 1 (ROCK1). AD mice was modeled through injection of β-amyloid 25-35 (Aβ25-35) into the lateral ventricle. After modeling, the mice were injected with altered TUG1 and/or miR-15a agomir lentiviruses. The spatial learning ability and memory ability of mice were detected through Morris water maze test. Hippocampal neuronal apoptosis and oxidative stress indicators in AD mice were then detected. The hippocampal neuron AD model was induced by Aβ25-35. Next, the neurons were, respectively, transfected with altered TUG1 vector and/or miR-15a mimics to determine the proliferation inhibition and apoptosis of hippocampal neurons. The interactions between TUG1 and miR-15a, and between miR-15a and ROCK1 were assessed using bioinformatic prediction, dual luciferase reporter gene assay and RNA-pull-down assay. In the animal models, Aβ25-35-induced mice exhibited decreased spatial learning and memory ability, obvious pathological injury, promoted hippocampal neuronal apoptosis and decreased antioxidant ability. TUG1 silencing and miR-15a elevation improved spatial learning ability and memory ability, ameliorated pathological injury, depressed neuronal apoptosis, and strengthened antioxidant ability of hippocampal neurons in AD mice. In cellular models, Aβ25-35-treated hippocampal neurons presented inhibited neuronal viability and promoted neuronal apoptosis. TUG1 silencing and miR-15a elevation increased viability and limited apoptosis of Aβ25-35-treated hippocampal neurons. TUG1 specifically bound to miR-15a, and miR-15a targeted ROCK1. Collectively, this study reveals that TUG1 knockdown restricts apoptosis of hippocampal neurons in AD by elevating miR-15a and suppressing ROCK1 expression, and provides a new therapeutic target for AD treatment.

Long Non-Coding RNA TUG1 Promotes Cell Proliferation and Inhibits Cell Apoptosis, Autophagy in Clear Cell Renal Cell Carcinoma via MiR-31-5p/FLOT1 Axis.

PurposeClear cell renal cell carcinoma (ccRCC) is a common urological carcinoma in adults. Long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been reported to be involved in the progression of diverse human cancers, including renal cell carcinoma (RCC). However, the biological mechanism of TUG1 was rarely reported in ccRCC.MethodsThe levels of TUG1, microRNA miR-31-5p and flotillin 1 (FLOT1) in ccRCC tissues and cells were detected by qRT-PCR. The interactions between miR-31-5p and TUG1 or FLOT1 were predicted by starBase v2.0 and TargetScan, respectively, which were further validated by RIP assay and RNA pull-down assay. Cell counting kit-8 (CCK-8), flow cytometry and Western blot were used to assess the effects of TUG1 on cell viability, apoptosis rate and the relative protein expression levels in ccRCC cells. In addition, the xenograft tumor assay was conducted to further verify the functions of TUG1 in ccRCC in vivo.ResultsTUG1 was dramatically up-regulated in ccRCC tissues and cells. TUG1 silencing inhibited cell proliferation and promoted cell apoptosis, autophagy in 786-0 and A498 cells. In addition, TUG1 depletion repressed tumor growth in vivo. Moreover, miR-31-5p was validated as a direct target of TUG1, and microRNA miR-31-5p inhibitor mitigated the effects of TUG1 knockdown on ccRCC progression. Furthermore, FLOT1 was verified to be negatively interacted with miR-31-5p. FLOT1 overexpression attenuated miR-31-5p-mediated inhibitory effect on cell proliferation and promotion effects on cell apoptosis, autophagy. The restoration experiment implicated that TUG1 positively modulated FLOT1 expression by sponging miR-31-5p.ConclusionAll data demonstrated that TUG1 promotes cell proliferation and inhibits cell apoptosis and autophagy in ccRCC by miR-31-5p/FLOT1 axis, which may provide a therapeutic target for ccRCC patients.

Long Noncoding RNA TUG1 Promotes the Function in ox-LDL-Treated HA-VSMCs via miR-141-3p/ROR2 Axis.

Background Atherosclerosis (AS) is a common severe disease around the world. The merging paper reported that long noncoding RNAs (lncRNAs) took part in diversified pathological processes of AS, although the mechanism remains unknown. This study is aimed at uncovering the profile of lncRNA taurine-upregulated gene 1 (TUG1), which has biological function, and potential mechanism in AS progression in vitro. Methods Oxidized low-density lipoprotein (ox-LDL) was used for AS model construction in vitro. Levels of lncRNA TUG1, miR-141-3p, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in AS tissues or in ox-LDL-treated vascular smooth muscle cells (HA-VSMCs). The biofunctional effects were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and transwell assays. The expression of proliferation-related proteins (CyclinD1, Ki-67) and metastasis-associated proteins (β-catenin, Vimentin) and ROR2 in cells was determined by western blot analysis. The potential binding sites were predicted by starBase software online and confirmed by dual-luciferase reporter analysis. Results The expression of TUG1 and ROR2 was promoted in AS tissues and ox-LDL-treated HA-VSMCs. While the low expression of miR-141-3p negatively correlated with that of TUG1 or ROR2 in AS tissues. Silencing of TUG1 inhibited the proliferation, migration, invasion, and metastasis in ox-LDL-treated HA-VSMCs. Moreover, the putative binding sites between miR-141-3p and TUG1 or ROR2 were predicted by starBase software online. Also, miR-141-3p deletion reversed the positive effects of TUG1 knockdown on cells. Besides, downregulation of miR-141-3p disrupted the biofunctional results from ROR2 silencing. Conclusion TUG1 enhanced the progression of AS in vitro by regulating the miR-141-3p/ROR2 axis.

Knockdown of lncRNA TUG1 Enhances Radiosensitivity of Prostate Cancer via the TUG1/miR-139-5p/SMC1A Axis.

BackgroundProstate cancer (PCa) is a common malignant tumor of the urinary system in males. LncRNA taurine-upregulated gene 1 (TUG1) has been verified to play a crucial role in progression and prognosis of PCa. However, the functional mechanism of TUG1 remains unclear with radiosensitivity of PCa.MethodsQuantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Moreover, colony formation assay was used to measure colony survival. Western blot was performed to detect the relative proteins expression. The interaction among variables was predicted by online tool starbase, and then confirmed using the dual luciferase reporter assay. A xenograft mouse model was constructed to investigate the effect of TUG1 on tumor growth in vivo.ResultsThe levels of lncRNA TUG1 and SMC1A were remarkably increased, while miR-139-5p was downregulated in PCa. Patients with high expression of TUG1 showed a lower survival rate and poor prognosis. Knockdown of TUG1 inhibited PCa cell proliferation and colony survival fraction, and promoted apoptosis. Downregulation of miR-139-5p reversed the effects of TUG1 deletion on proliferation, apoptosis and colony survival fraction in PCa cells treated with 4 Gy of X-ray radiation. Moreover, TUG1 sponged miR-139-5p to regulate SMC1A expression. SMC1A deletion blocked the effects of TUG1 on the progression of PCa cells treated with 4 Gy of X-ray radiation. The tumor volume and weight were illustriously reduced with radiation and TUG1 silencing in xenograft model.ConclusionKnockdown of lncRNA TUG1 enhanced radiosensitivity in PCa via the TUG1/miR-139-5p/SMC1A axis. It may become a promising target for PCa treatment.

<p>LncRNA TUG1 Regulates Cell Viability and Death by Regulating miR-193a-5p/Rab10 Axis in Acute Myeloid Leukemia</p>

BackgroundAcute myeloid leukemia (AML) is a serious threat to human health. Long non-coding RNA (lncRNA) Taurine-Upregulated Gene1 (TUG1) has been reported to participate in the development and progression of several cancers, including AML. Herein, we aimed to investigate the pathognomonic role of TUG1 in AML cells and its potential mechanistic pathway.MethodsQuantitative real-time PCR (qRT-PCR) assay was applied to detect the expression levels of lncRNA TUG1, miR-193a-5p and Rab10 in AML bone marrow and cell lines. The CCK-8 assay was conducted to assess the cell viability of AML HL-60 and NB4 cells and cell apoptotic assay was performed to assess the cell death. Dual-luciferase reporter assay was carried out to clarify the relationships among TUG1, miR-193a-5p and Rab10. Also, the protein level of Rab10 was examined by Western blot assay.ResultsLncRNA TUG1 was up-regulated in AML bone marrow and cells. Functional analysis showed that the silencing of TUG1 suppressed cell viability, while promoted cell death in AML HL-60 and NB4 cells. TUG1 targeted miR-193a-5p and negatively regulated miR-193a-5p expression. Overexpressed miR-193a-5p resulted in the decrease of cell viability and the increase in the cell death in AML cells. Restoration experiments proved that TUG1 regulated the cell viability and death of AML cells through regulating the miR-193a-5p/Rab10 axis. Rab10 was a direct target of miR-193a-5p and was inversely regulated by miR-193a-5p. TUG1 regulated the cell viability and death of AML cells through upregulating Rab10.ConclusionSilencing of lncRNA TUG1 induces a cytotoxic effect on AML cell lines through sponging miR-193a-5p and the suppression of Rab10.

Long Non-Coding RNA Taurine Upregulated Gene 1 (TUG1) Downregulation Constrains Cell Proliferation and Invasion through Regulating Cell Division Cycle 42 (CDC42) Expression Via MiR-498 in Esophageal Squamous Cell Carcinoma Cells.

BackgroundEsophageal squamous cell carcinoma (ESCC) is a malignant tumor of the gastrointestinal tract. Taurine upregulated gene 1 (TUG1), a long non-coding (lnc) RNA, also known as LIN00080 or TI-227H, was connected with the tumorigenesis of various diseases. Hence, we plumed the role and molecular mechanism of TUG1 in the progression of ESCC.Material/MethodsExpression patterns of TUG1, microRNA-498 (miR-498), and cell division cycle 42 (CDC42) mRNA were assessed using quantitative real time polymerase chain reaction (qRT-PCR). The expression level of CDC42 protein was evaluated via western blot analysis. Cell proliferation and invasion were determined with Cell Counting Kit-8 (CCK-8) assay or Transwell assay. The relationship between miR-498 and TUG1 or CDC42 was predicted by online bioinformatics database LncBase Predicted v.2 or microT-CDS and confirmed through dual-luciferase reporter system or RNA immunoprecipitation assay (RIP).ResultsTUG1 and CDC42 were upregulated while miR-498 was strikingly decreased in ESCC tissues and cells (P<0.0001). Besides, TUG1 suppression blocked the proliferation and invasion of ESCC cells (P<0.001). Importantly, TUG1 decrease restrained CDC42 expression via binding to miR-498 in ESCC cells. Also, the suppressive impacts of TUG1 silencing on the proliferation and invasion of ESCC cells were mitigated by miR-498 reduction. Meanwhile, the repression of proliferation and invasion induced by miR-498 elevation was weakened by CDC42 overexpression.ConclusionsInhibition of TUG1 hampered cell proliferation and invasion by downregulating CDC42 via upregulating miR-498 in ESCC cells. Thus, TUG1 might be an underlying therapeutic target for ESCC.

Emodin relieved lipopolysaccharide-evoked inflammatory damage in WI-38 cells by up-regulating taurine up-regulated gene 1.

Neonatal pneumonia (NP) has a high fatality rate in neonatal illness. This research investigated the functions of emodin on lipopolysaccharide (LPS)-evoked inflammatory injury in WI-38 cells. Cell counting kit-8 (CCK-8) assay and flow cytometry were utilized for examining the impacts of LPS and emodin on viability and apoptosis, respectively. Taurine up-regulated gene 1 (TUG1) level was altered through cell transfection and investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, RT-qPCR, western blot and enzyme-linked immunosorbent assay (ELISA) were utilized for investigating expressions of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. Western blot was carried out for investigating the levels of Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3 and NF-κB and p38MAPK pathway-related proteins. LPS treatment restrained cell viability, enhanced apoptosis, and expressions of inflammation-related IL-6 and MCP-1. Emodin alleviated LPS-evoked inflammatory injury and restrained the NF-κB and p38MAPK pathways. Furthermore, emodin positively regulated TUG1 expression and TUG1 silencing could reverse the efficacy of emodin on IL-6 and MCP-1 expressions. Finally, TUG1 regulates the expression of inflammatory factors through NF-κB and p38MAPK pathways. Emodin alleviated LPS-evoked inflammatory injury by raising TUG1 expression via NF-κB and p38MAPK pathways in WI-38 cells.

Long non-coding TUG1 accelerates prostate cancer progression through regulating miR-128-3p/YES1 axis.

Dysregulation of long non-coding RNAs (lncRNAs) is being found to have relevance to human cancers, including prostate cancer (PCa). Taurine-upregulated gene 1 (TUG1) has been demonstrated to have a potential oncogenic role in PCa. Then the aim of this study was to investigate the molecular mechanisms of TUG1 on PCa progression. The expression levels of TUG1, YES proto-oncogene 1 (YES1) mRNA and miR-128-3p were assessed using quantitative real-time polymerase chain reaction. Cell proliferation ability, apoptosis, and migration and invasion capacities were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry and transwell assay, respectively. Western blot analysis was employed to evaluate the indicated proteins levels. The interaction between miR-128-3p and TUG1 or YES1 was determined using the Dual-Luciferase reporter assay. In vivo assay was used to observe the effect of TUG1 on tumor growth in vivo. Our data indicated that TUG1 was upregulated in PCa tissues and cells and predicted poor prognosis. TUG1 knockdown weakened PCa cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and accelerated cell apoptosis in vitro. Mechanistically, TUG1 directly interacted with miR-128-3p and miR-128-3p mediated the regulatory effects of TUG1 depletion on PCa cell progression. YES1 was a direct target of miR-128-3p and TUG1 modulated YES1 expression by sponging miR-128-3p. Moreover, TUG1 silencing repressed PCa cell progression in vitro through YES1. Additionally, TUG1 silencing mitigated tumor growth in vivo. Our study suggested that TUG1 silencing retarded PCa cell progression in vitro and tumor growth in vivo through miR-128-3p/YES1 axis, showing that targeting TUG1 might be a novel therapeutic strategy for PCa management.

Silencing of long noncoding RNA TUG1 inhibits viability and promotes apoptosis of acute myeloid leukemia cells by targeting microRNA-221-3p/KIT axis.

Acute myeloid leukemia (AML) is a hematological malignancy. This study was attempted to uncover the effects of long noncoding RNA taurine-upregulated gene1 (TUG1) on the viability and apoptosis of AML cells. QRT-PCR was implemented to examine the expression of TUG1, miR-221-3p and KIT in AML. The correlation between TUG1 and clinicopathological features of AML patients was evaluated. The effect of TUG1 on AML cells were studied by RNA interference approach. AML cells were transfected with miR-221-3p mimic and miR-221-3p inhibitor, respectively. Then the viability and apoptosis of AML cells were examined by MTT and flow cytometry assay, respectively. Additionally, dual-luciferase reporter assay was used to confirm the interactions among TUG1, miR-221-3p and KIT. Western blot was applied to analyze protein expression of KIT. The expression of TUG1 and KIT was up-regulated in AML, but miR-221-3p was down-regulated. TUG1 expression had obviously correlation with World Health Organization (WHO) grade in AML patients. The functional experiment stated that TUG1 silencing suppressed the viability and accelerated the apoptosis of AML cells. Moreover, the mechanical experiment demonstrated that TUG1 and KIT were both targeted by miR-221-3p with the complementary binding sites at 3'UTR. Up-regulation of miR-221-3p inhibited the protein expression of KIT. Furthermore, in the feedback experiment, miR-221-3p inhibition or KIT overexpression reversed the repression of tumor behavior induced by TUG1 silencing. TUG1 silencing retarded viability and promoted apoptosis of AML cells via regulating miR-221-3p/KIT axis, providing a potential therapeutic target for AML.

Long non-coding RNA TUG1 regulates the progression and metastasis of osteosarcoma cells via miR-140-5p/PFN2 axis.

Osteosarcoma (OS) is a frequently occurred tumor. Recently, increasing reports disclosed that long non-coding RNA taurine upregulated gene 1 (TUG1) was associated with OS development. Nevertheless, the precise regulatory pattern was not completely understood. Hence, we aimed to investigate the biological role of TUG1 in OS tumorigenesis. The levels of TUG1, microRNA-140-5p (miR-140-5p), and Profilin 2 (PFN2) were measured via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the protein level of PNF2 was assessed using Western blot. In addition, MTT assay was employed to detect the ability of cell proliferation in MG63 and U2OS cells. Cell migration and invasion were estimated adopting transwell assay. Moreover, the Dual-Luciferase reporter assay was performed to verify the interrelation between miR-140-5p and TUG1 or PFN2. TUG1 and PFN2 levels were evidently upregulated in OS tissues and cell lines. The knockdown of either TUG1 or PFN2 could restrain cell proliferation, migration, and invasion in OS cells. In addition, miR-140-5p was a target of TUG1 to regulate PFN2. The functions of PFN2 knockdown in cell behaviors were rescued after co-transfection with either miR-140-5p inhibitor or overexpression vector of TUG1. Importantly, TUG1 silencing could impede tumor progression in vivo. TUG1 modulated cell proliferation, migration, and invasion via miR-140-5p/PFN2 axis in OS progression, which might trigger the development of therapeutic strategies for the treatment of OS.

Inhibition of TUG1/miRNA-299-3p Axis Represses Pancreatic Cancer Malignant Progression via Suppression of the Notch1 Pathway.

Taurine-upregulated gene 1 (TUG1) is reported to be upregulated and contributes to the progression of Pancreatic cancer(PC) by serving as an oncogene. Our aims were to explore the precise mechanism of TUG1 involved in PC pathogenesis. TUG1 and miR-299-3p expression profiles were measured by qRT-PCR. The direct interactionbetween TUG1 and miR-299-3p was explored by luciferase reporter assay. MTTassay, flow cytometry analysis, caspase-3 activity assay, Transwell invasion assay and wound healing assay were performed to evaluate cell proliferative ability, apoptosis, caspase-3 activity, invasion and migration, respectively. Western blot was conducted to examine the expressions of Ki67, Bax, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, N-cadherin, Snail, Notch1, Survivin, and CyclinD1. In addition, animal experiments were also implemented. TUG1 was highly expressed, while miR-299-3p was underexpressed in PC tissues and PC cells. Furthermore, the significant increase of TUG1in PC tissues of advanced patients (stage 3/4) was observed compared to patients (stage 1/2). TUG1 was negatively correlated with miR-299-3p expression in PC tissues. Moreover, TUG1 functioned as a molecular sponge of miR-299-3p to repress its expression. TUG1 knockdown suppressed cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT), and induced apoptosis in PC cells, and repressed tumor growth and EMT in PC xenograft models, which were reversed following reintroduction with anti-miR-299-3p. Furthermore, we found that TUG1 silencing inactivated the Notch1 pathway in PC by upregulating miR-299-3p. The results reported that inhibition of TUG1/miR-299-3p axis suppressed PC malignant progression via suppression of the Notch1 pathway.

LncRNA TUG1 influences osteoblast proliferation and differentiation through the Wnt/β-catenin signaling pathway.

Long non-coding ribonucleic acids (lncRNAs) play a vital role in bone development, but the function of lncRNA taurine up-regulated gene 1 (TUG1) in osteoblast proliferation and differentiation is still unknown. The expression of TUG1 and the messenger RNA (mRNA) expressions of the Wnt/β-catenin signaling pathway markers [Runt-related transcription factor 2 (Runx2), Frizzled-2, axis inhibition protein 2 (Axin 2) and β-catenin] at 0 d, 1 d, 7 d and 14 d after in vitro culture of osteoblasts were detected, respectively, by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The effects of TUG1 on the Wnt/β-catenin signaling pathway markers and osteoblast proliferation and differentiation were studied through the silencing of TUG1 by short hairpin TUG1 (shTUG1). Furthermore, the effects of the Wnt/β-catenin signal on osteoblast proliferation and differentiation was verified by Wnt/β-catenin signal inhibitors. With the continuous differentiation of osteoblasts, the level of TUG1 was significantly increased. The mRNA levels of the Wnt/β-catenin signaling pathway markers (Runx2, Frizzled-2, Axin 2 and β-catenin) also showed the same increasing trend. ShTUG1 notably reduced the activity of alkaline phosphatases (ALPs), the levels of osteocalcin and osteopontin and osteoblast proliferation activity. In addition, the silencing of TUG1 by shTUG1 resulted in significant reductions in the proteins of the Wnt/β-catenin signaling pathway markers (Runx2, Frizzled-2, Axin 2 and β-catenin), and Wnt/β-catenin inhibitors markedly reduced osteoblast proliferation and differentiation activity. LncRNA TUG1 inhibition can suppress the Wnt/β-catenin signaling pathway and reduce osteoblast proliferation and differentiation.

LncRNA TUG1 Promotes Cisplatin Resistance by Regulating CCND2 via Epigenetically Silencing miR-194-5p in Bladder Cancer

Taurine-upregulated gene 1 (TUG1) has been involved in tumorigenesis of several human cancers, but its precise biological role in bladder cancer remains largely elusive. In this study, we found that TUG1 was upregulated in bladder cancer and the expression of TUG1 was positively and negatively correlated with CCND2 and miR-194-5p, respectively. MiR-194-5p expression was frequently decreased through promoter hypermethylation, while it was epigenetically increased following cisplatin and 5-aza-2′-deoxycytidine (5-Aza-DC) treatment. Furthermore, knockdown of TUG1 attenuated the expression of epigenetic regulator Enhancer of zeste homolog 2 (EZH2), and it alleviated the promoter hypermethylation of miR-194-5p and induced its expression. Increased miR-194-5p expression or decreased TUG1 expression significantly sensitized bladder cancer cells to cisplatin, inhibited the proliferation, and induced apoptosis. Besides, CCND2 was a direct target of miR-194-5p, while miR-194-5p was regulated by TUG1. CCND2 could partially restore the tumor-suppressive effects on cell proliferation and cisplatin resistance following TUG1 silencing. Additionally, TUG1 expression was correlated with clinical stage, lymphatic metastasis, and patient prognosis. In conclusion, TUG1 promotes bladder cancer cell growth and chemoresistance by regulating CCND2 via EZH2-associated silencing of miR-194-5p. Our study may be conducive to elucidating the molecular mechanism of and providing novel therapeutic target and biomarker for bladder cancer.

Upregulation of Long Noncoding RNA TUG1 Promotes Bladder Cancer Cell Proliferation, Migration, and Invasion by Inhibiting miR-29c.

Bladder cancer (BC) is one of the leading causes of cancer-related deaths in the world. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) plays an important role in the development and progression of numerous cancers, including BC. However, the exact role of TUG1 in modulating BC progression is still poorly known. In this study, we found that TUG1 was upregulated and microRNA-29c (miR-29c) was downregulated in BC tissues and cell lines. Overexpression of TUG1 promoted the cell proliferation of T24 and EJ cells, whereas TUG1 knockdown had the opposite effect. Upregulation of TUG1 obviously facilitated the migration and invasion of T24 and EJ cells. In contrast, TUG1 silencing repressed the migration and invasion of T24 and EJ cells. Furthermore, TUG1 knockdown markedly increased the expression of miR-29c in vitro. On the contrary, overexpression of TUG1 remarkably decreased the expression of miR-29c. Transfection with plasmids containing mutant TUG1 has no effect on the expression of miR-29c. There were direct interactions between miR-29c and the binding sites of TUG1. In addition, the inhibitory effects of small interfering RNA specific for TUG1 on BC cell proliferation, migration, and invasion were reversed by downregulation of miR-29c. Collectively, our study strongly demonstrates that TUG1 promotes BC cell proliferation, migration, and invasion by inhibiting miR-29c, suggesting that lncRNA TUG1 may be a promising target for BC gene therapy.

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.

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.

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.

Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration.

Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical roles in carcinogenesis and progression, have emerged as important gene expression modulators. Recent evidence indicates that lncRNA taurine‐upregulated gene 1 (TUG1) functions as an oncogene in numerous types of human cancers. However, its function in the development of cervical cancer remains unknown. The aim of this research was to investigate the clinical significance and biological functions of TUG1 in cervical cancer. TUG1 was found to be significantly upregulated in cervical cancer tissues and four cervical cancer cell lines by quantitative real‐time polymerase chain reaction (qRT‐PCR). Elevated TUG1 expression was correlated with larger tumor size, advanced international federation of gynecology and obstetrics (FIGO) stage, poor differentiation, and lymph node metastasis. Furthermore, knockdown of TUG1 suppressed cell proliferation with activation of apoptosis, in part by regulating the expression of Bcl‐2 and caspase‐3. Silencing of TUG1 inhibited cell migration and invasion via the progression of epithelial–mesenchymal transition (EMT). Taken together, our findings indicate that TUG1 acts as an oncogene in cervical cancer and may represent a novel therapeutic target.