Taurine Upregulated Gene 1 Knockdown Research Articles

TUG1 Regulates Pulmonary Arterial Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease, characterized by a persistent elevation of pulmonary arterial pressure and pulmonary vascular remodelling. Recent studies implicated that long noncoding RNAs (lncRNAs) play important roles in the development of various diseases. However, the underlying mechanisms of lncRNAs in PAH remain unclear. Here we show evidence for the modulation of human pulmonary smooth muscle cell (HPASMC) proliferation and vascular remodelling by lncRNA taurine upregulated gene1 (TUG1). MethodsTUG1 expression and localization was detected by real-time polymerase chain reaction (PCR) and fluorescence in situ hybridization. Proliferation and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), western blot, bromodeoxyuridine incorporation, flow cytometry, scratch-wound assay, 4′,6-diamidino-2-phenylindole (DAPI), and caspase-3 activity. Luciferase activity and microscale thermophoresis were used to identify biomolecular interactions. The right ventricular systolic pressure and right ventricular hypertrophy were measured to evaluate cardiopulmonary function. ResultsTUG1 was upregulated in the pulmonary arteries of mice after a hypoxic assault and showed a significant increase in patients with PAH. TUG1 knockdown significantly prevented the development of PAH in vivo. Moreover, TUG1 promoted the proliferative responses of HPASMCs, including cell viability, 5-bromodeoxyuridine incorporation, the expression of proliferating cell nuclear antigen, and cell-cycle progression. All these functions of TUG1 were likely to be associated with miR-328. ConclusionsThe present study indicates that TUG1, a novel potential target for the treatment of PAH, is necessary for HPASMC proliferation and pulmonary vascular remodelling.

Anticancer potential of TUG1 knockdown in cisplatin-resistant osteosarcoma through inhibition of MET/Akt signalling

Development of cisplatin (DDP)-resistance is a major challenge that largely limits the efficacy of chemotherapy for osteosarcoma. LncRNA Taurine up-regulated gene 1 (TUG1) is a recently identified oncogenic lncRNA that has been involved in chemo-resistance of various cancers. In this study, over-expression of TUG1 was found in two osteosarcoma cell lines resistant to DDP (Saos-2/DDP, MG-63/DDP). Knockdown of TUG1 inhibited the DDP-resistance and promoted the cytotoxicity and apoptosis induced by DDP in Saos-2/DDP and MG-63/DDP cells. TUG1 knockdown also markedly inhibited the expression level of MET and p-Akt. In conclusion, knockdown of TUG1 suppressed cell growth and increased apoptotic rate under DDP treatment possibly via regulating MET/Akt signalling pathway.

Knockdown of TUG1 by shRNA inhibited renal cell carcinoma formation by miR-299–3p/VEGF axis in vitro and in vivo

Renal cell carcinoma (RCC) is one of the top ten deadly malignancies in the world. The long non-coding RNA taurine up-regulated gene 1 (TUG1) is a transcript that is up-regulated by taurine. There is ample evidence that TUG1 plays a crucial role in the progression of various cancers. This study aimed to investigate the role of TUG1 in RCC and its underlying molecular mechanisms. In the current study, knockdown of TUG1 by shRNA (sh-TUG1) significantly inhibited proliferation, invasion, migration and EMT processes of ACHN cells and OS-RC-2 cells, and induced apoptosis. Besides, bioinformatics analysis revealed that miR-299–3p is a target of TUG1. TUG1 overexpression (LV-TUG1) significantly inhibited the expression of miR-299–3p, whereas sh-TUG1 showed the opposite effect. Dual luciferase reporter assay further confirmed the targeting relationship between TUG1 and miR-299–3p. In addition, vascular endothelial growth factor (VEGFA) is a target of miR-299–3p. Knockdown of VEGFA (si-VEGFA) significantly inhibited the proliferation and motility of ACHN cells, and induced apoptosis. RT-qPCR results showed that sh-TUG1 similarly inhibited VEGFA expression. Further functional analysis indicated that sh-TUG1 inhibited tumorigenesis by down-regulating VEGFA levels. However, LV-TUG1 showed the opposite effects. Furthermore, animal experiments have shown that sh-TUG1 inhibited tumor growth and metastasis and induces apoptosis in vivo. These results indicate that sh-TUG1 inhibited renal cell carcinoma formation by miR-299–3p/VEGF axis in vitro and in vivo. Taken together, all of these results reveal a novel mechanism of TUG1 in RCC tumorigenesis, suggesting that targeted drugs for TUG1 provides a new direction for the treatment of RCC.

Knockdown of long noncoding RNA-taurine-upregulated gene 1 inhibits tumor angiogenesis in ovarian cancer by regulating leucine-rich α-2-glycoprotein-1.

To investigate the role of long noncoding RNA taurine-upregulated gene 1 (TUG1) on ovarian cancer-induced angiogenesis and to explore possible signaling pathways. Ovarian cancer cell line SKOV3 or CAOV3 was transfected with short hairpin-TUG1 to suppress TUG1 expression. Supernatant from cultured cancer cells was used as a condition medium to incubate endothelial cell line human umbilical vein endothelial cells, whose proliferation rate was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Migration and invasion of endothelial cells were examined by wound healing and Transwell assays, followed by in-vitro angiogenesis assay. One of the secretory factors mediating angiogenesis, leucine-rich α-2-glycoprotein-1 (LRG1), was measured in ovarian cancer cells. Signaling pathway mediating angiogenesis was further detected by western blotting. TUG1 was down-regulated in ovarian cancer cells by short hairpin RNA. Conditional medium originating from TUG1-knockdown cancer cells led to suppressed proliferation, migration, or invasion of endothelial cell line human umbilical vein endothelial cells. LRG1 expression and secretion was suppressed in ovarian cancer cells after TUG1 knockdown. Moreover, recombinant LRG1 rescued TUG1 knockdown-induced angiogenesis inhibition, and LRG1 probably mediated angiogenesis by tumor growth factor-β signaling pathway in endothelial cells. Long noncoding RNA-TUG1 mediates angiogenesis of endothelial cells by regulating LRG1 secretion from ovarian cancer cells partially through tumor growth factor-β pathway. Our results indicate the potency of TUG1 as a biomarker and therapeutic target for tumor-induced angiogenesis.

LncRNA TUG1 promotes cisplatin resistance in esophageal squamous cell carcinoma cells by regulating Nrf2.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy with poor prognosis. The drug resistance compromises the efficacy of chemotherapy for ESCC. Long non-coding RNA taurine upregulated gene 1 (TUG1) has been identified as a promoter of cancer progression and chemotherapy resistance in many malignancies. However, the exact role of TUG1 in ESCC chemotherapy resistance remains unclear. In this study, we showed that TUG1 expression in TE-1-derived cisplatin (DDP)-resistant (TE-1/DDP) cells was higher than that in TE-1 cells. Furthermore, TUG1 promoted DDP resistance in TE-1 and TE-1/DDP cells by promoting cell proliferation, suppressing cell apoptosis, and elevating protein expression of the classical multi-drug resistance-related P-gp. In contrast, TUG1 knockdown exerted an opposite effect. Mechanistically, RNA pull-down and RNA immunoprecipitation assays confirmed that TUG1 directly bound to nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein and elevated Nrf2 protein expression. Moreover, Nrf2-neutralizing antibody effectively reversed the TUG1 overexpression-mediated promotion of ESCC cell resistance to DDP. In conclusion, our findings demonstrated that TUG1 promoted ESCC cell resistance to DDP, at least in part, through upregulating Nrf2.

Long noncoding RNA TUG1 promotes proliferation and inhibits apoptosis in multiple myeloma by inhibiting miR-29b-3p.

Background: Long non-coding RNA taurine up-regulated gene 1 (TUG1) was reportedly involved in initiation and development of several cancers. However, its function and molecular mechanisms in multiple myeloma (MM) are still unclear. The present study aimed to determine the expression status, biological function, and potential mechanisms of TUG1 in the progression of MM.Materials and methods: The expression levels of TUG1 were examined in MM samples and cell lines by real-time quantitative PCR. The effects of TUG1 on MM cells proliferation and apoptosis were assessed using Cell Counting Kit-8 assay and flow cytometry respectively. MiRNAs-targeted sites in TUG1 were screened by Starbase2.0 and were identified by RNA immunoprecipitation assay combined with luciferase reporter assay.Results: The expression levels of TUG1 were markedly increased in MM samples and cell lines. Knockdown of TUG1 significantly suppressed the proliferation, induced cell cycle arrest at G1/G0 phase, and promoted apoptosis of MM cells. In exploring the regulatory mechanism, miR-29b-3p was confirmed to be a direct target of TUG1, and repression of miR-29b-3p could partially rescue the effect TUG1 knockdown on MM cell proliferation, cycle, and apoptosis. In addition, TUG1 positively modulated histone deacetylases 4 (HDAC4, a target of miR-29b-3p) expression through sponging of miR-29b-3p in MM cells.Conclusion: These findings suggested that TUG1 exerted an oncogenic role in MM by acting as a competing endogenous RNA of miR-29b-3p, and implied the potential application of TUG1 in treatment for MM.

TUG1 promotes the development of prostate cancer by regulating RLIM.

The aim of this study was to investigate the specific role of Taurine up-regulated gene 1 (TUG1) in the development of prostate cancer (PCa), and to explore its underlying mechanism. The serum level of TUG1 in healthy subjects, benign prostatic hyperplasia (BPH) patients and PCa patients was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between TUG1 expression and clinical indexes of PCa patients was analyzed. TUG1 expression in PCa cells and human normal prostate cells was determined by qRT-PCR as well. Overexpression or knockdown of TUG1 was achieved by liposomal transfection. Subsequently, the regulatory effects of TUG1 on the proliferative and migratory capacities of DU145 cells were accessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and transwell assay, respectively. An online software was used to predict whether RLIM could be regulated by TUG1, which was further verified by qRT-PCR. After RLIM knockdown in DU145 cells, the proliferative and migratory capacities were also determined. Finally, Western blot was conducted to determine relative protein expressions in the TGF-β1/Smad pathway after altering TUG1 expression in DU145 cells. TUG1 was highly expressed in serum samples of PCa patients when compared with healthy subjects and BPH patients. Besides, TUG1 expression in PCa patients with Gleason ≥ 7 was significantly higher than those with Gleason < 7. Meanwhile, TUG1 expression in PCa patients was remarkably higher than that of BPH patients at the PSA grey zone (4-10 ng/mg). ROC curves indicated that TUG1 might be a crucial hallmark to distinguish PCa patients from BPH patients and healthy subjects. The overexpression of TUG1 markedly promoted the proliferative and migratory capacities of DU145 cells. However, knockdown of TUG1 obtained the opposite results. QRT-PCR confirmed that TUG1 was positively correlated with RLIM at the mRNA level. RLIM knockdown significantly inhibited the proliferative and migratory capacities of DU145 cells. Furthermore, knockdown of TUG1 in DU145 cells markedly down-regulated TGF-β1 and p-Smad2, whereas up-regulated p-Smad7. TUG1 is highly expressed in peripheral blood of PCa patients, which can serve as a potential diagnostic marker for PCa. The overexpression of TUG1 promotes the proliferative and migratory capacities of PCa cells. Furthermore, TUG1 promotes the development of PCa by regulating RLIM through the TGF-β1/Smad pathway.

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.

TUG1 knockdown enhances adriamycin cytotoxicity by inhibiting glycolysis in adriamycin-resistant acute myeloid leukemia HL60/ADR cells.

Taurine-upregulated gene 1 (TUG1) has been reported as an oncogenic long non-coding RNA (lncRNA) in acute myeloid leukemia (AML). Nevertheless, the roles and molecular mechanism of TUG1 in drug resistance of AML cells are still unclear. Glycolysis level was evaluated by detecting glucose consumption and lactate production. qRT-PCR and Western blot were performed to detect TUG1, hexokinase2 (HK2) and pyruvate kinase isoenzyme M2 (PKM2) expressions. Adriamycin (ADR) cytotoxicity and apoptosis were assessed by MTT assay and flow cytometry, respectively. The changes of the protein kinase B (Akt) pathway were determined by Western blot analysis of phosphorylated-Akt (p-Akt) (ser473) and Akt. Our results showed that glycolysis was increased in HL60/ADR cells, as evidenced by the elevated glucose consumption and lactate production, as well as the increased HK2 and PKM2 expressions at mRNA and protein levels. TUG1 was up-regulated in HL60/ADR cells and TUG knockdown inhibited glycolysis. TUG1 knockdown enhanced ADR-induced cytotoxicity and apoptosis in HL60/ADR cells. TUG1 knockdown inhibited the Akt pathway and activation of the Akt pathway by 740Y-P attenuated the effects of TUG1 knockdown on ADR-induced cytotoxicity and apoptosis, as well as glycolysis in HL60/ADR cells. Taken together, TUG1 knockdown enhances adriamycin cytotoxicity in HL60/ADR cells via inhibiting the glycolysis by inactivating the Akt pathway.

LncRNA TUG1 Promotes the Intervertebral Disc Degeneration and Nucleus Pulposus Cell Apoptosis Though Modulating miR-26a/HMGB1 Axis and Regulating NF-κB Activation

Background: The core feature of intervertebral disc degeneration (IDD) is the reduction in the number of nucleus pulposus cells (NPCs) and the loss of extracellular matrix (ECM). Emerging studies have shown that long-chain non-coding RNAs (lncRNAs) taurine upregulated gene 1 (TUG1) plays a key role in the development of IDD. However, the relevant mechanisms of TUG1 in the development of IDD are not yet clear. Objective: This study investigated the effect of TUG1 on apoptosis and ECM degradation of human degenerative intervertebral disc NPCs and its mechanism. Methods: The expression of TUG1 in the human IDD NP tissues and NPCs was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of overexpression or knockdown of TUG1 on cell proliferation and apoptosis were examined by EdU assay and flow cytometry, respectively. Utilizing bioinformatics methods, luciferase activity assay, the possible interacted miRNA and Mrna were explored. Western blot analysis determined the expression levels of collagen II, aggrecan, MMP-3 and MMP-13. Additionally, the effect of TUG1 on NF-κB pathway was analyzed by western blot assay and immunofluorescence staining. Results: The expression of TUG1 and HMGB1 protein in human degenerative disc NP tissues and NPCs was significantly increased, while the level of miR-26a was significantly decreased. Overexpression of TUG1 inhibited the proliferation while promoted apoptosis and ECM degradation of human degenerative intervertebral disc NPCs. Simultaneously, the effect of TUG1 knockdown on NPCs was opposite. Interestingly, TUG1 acts as an endogenous sponge to down-regulate the expression of miR-26a in NPCs by direct binding to miR-26a.Overexpression of miR-26a reversed the effect of TUG1 overexpression on apoptosis and ECM degradation. Additionally, HMGB1 is a target gene of miR-26a.The increased expression of HMGB1 induced by TUG1 overexpression can be reversed by the introduction of miR-26a mimic. Overexpression of TUG1 significantly upregulated the expression of p65 in the nucleus, and overexpression of TUG1 partially abolished the inhibition of NF-κB by NF-κB specific inhibitor QNZ pretreatment. Conclusion: TUG1 can promote the apoptosis and ECM degradation of degenerated intervertebral disc NPCs by regulating the miR-26a/HMGB1, which may be involved in the activation of NF-κB pathway. Funding Statement: The authors stated that no funding was received. Declaration of Interests: The authors report no conflicts of interest in this work. Ethics Approval Statement: This study was approved by the Ethics Committee of Chinese Academy of Medical Sciences Peking Union Medical College Hospital.

Knockdown of long non-coding RNA TUG1 suppresses nasopharyngeal carcinoma progression by inhibiting epithelial-mesenchymal transition (EMT) via the promotion of miR-384

Nasopharyngeal carcinoma (NPC) is a cancer arising from the nasopharynx epithelium. Long non-coding RNAs (lnc RNA) play a critical role in various biological processes such as cell growth, embryonic development, and tumorigenesis. In the study, for the first time, we discovered that lnc RNA taurine upregulated gene 1 (TUG1) exhibited higher expression levels in NPC tissues and NPC cell lines than in normal nasopharyngeal epithelial tissues and normal nasopharyngeal cell line. In addition, patients with NPCs showing higher levels of TUG1 had worse overall survivals. Further, suppressing TUG1 expression markedly reduced the cell proliferation, migration and invasion; however, TUG1 over-expression significantly enhanced the proliferation, migration and invasion in NPC cells. TUG1 knockdown-inhibited epithelial-mesenchymal transition (EMT) was evidenced by the reduced expression of Vimentin, N-cadherin and transforming growth factor (TGF)-β1, while the enhanced level of E-cadherin. The results of luciferase reporter analysis verified that miR-384 was a direct target of TUG1 in NPC, and was down-regulated in NPC tissues, exhibiting suppressive role in cell proliferation, migration and invasion. In vivo, TUG1 knockdown reduced tumor growth via the regulation of miR-384 by restraining EMT development. In conclusion, our findings suggested that there was a negative correlation between TUG1 and miR-384 in NPC patients. TUG1 might be an effective candidate for use in NPC diagnosis, prognosis and treatment.

TUG1 confers cisplatin resistance in esophageal squamous cell carcinoma by epigenetically suppressing PDCD4 expression via EZH2

BackgroundIncreasing evidence has suggested the involvement of long non-coding RNA taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in esophageal squamous cell carcinoma (ESCC) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in cisplatin (DDP) resistance of ESCC and discover the underlying molecular mechanism.ResultsOur study revealed that TUG1 was up-regulated in DDP-resistant ESCC tissues and cells. High TUG1 expression was correlated with poor prognosis of ESCC patients. TUG1 knockdown improved the sensitivity of ECA109/DDP and EC9706/DDP cells to DDP. Moreover, TUG1 could epigenetically suppress PDCD4 expression via recruiting enhancer of zeste homolog 2. PDCD4 overexpression could mimic the functional role of down-regulated TUG1 in DDP resistance. PDCD4 knockdown counteracted the inductive effect of TUG1 inhibition on DDP sensitivity of ECA109/DDP and EC9706/DDP cells. Furthermore, TUG1 knockdown facilitated DDP sensitivity of DDP-resistant ESCC cells in vivo.ConclusionTUG1 knockdown overcame DDP resistance of ESCC by epigenetically silencing PDCD4, providing a novel therapeutic target for ESCC.

TUG1 confers Adriamycin resistance in acute myeloid leukemia by epigenetically suppressing miR-34a expression via EZH2

Increasing evidence has suggested the involvement of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in acute myeloid leukemia (AML) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in Adriamycin (ADR) resistance of AML and discover the underlying molecular mechanism. Our study revealed that TUG1 was up-regulated in ADR-resistant AML tissues and cells. High TUG1 expression was correlated with poor prognosis of AML patients. TUG1 knockdown improved the sensitivity of HL60/ADR cells to ADR. Moreover, TUG1 could epigenetically suppress miR-34a expression via recruiting Enhancer of zeste homolog 2 (EZH2). miR-34a overexpression could mimic the functional role of down-regulated TUG1 in ADR resistance. miR-34a knockdown counteracted the inductive effect of TUG1 inhibition on ADR sensitivity of HL60/ADR cells. Furthermore, TUG1 knockdown facilitated ADR sensitivity of ADR-resistant AML cells in vivo. In summary, TUG1 knockdown overcame ADR resistance of AML by epigenetically enhancing miR-34a expression, providing a novel therapeutic target for AML.

Long Noncoding RNA TUG1/miR-29c Axis Affects Cell Proliferation, Invasion, and Migration in Human Pancreatic Cancer.

Given the low resection rate and chemoresistance of patients with pancreatic cancer (PC), their survival rates are typically poor. Long noncoding RNAs (lncRNAs) have recently been shown to play an important role in tumourigenesis and human cancer progression, including in PC. In this study, we aimed to investigate the role of taurine-upregulated gene 1 (TUG1) in PC. A quantitative polymerase chain reaction was used to analyse TUG1 expression in PC tissues and peritumoural normal tissues. TUG1 was overexpressed in PC tissues compared with that in peritumoural normal tissues, and the high expression of TUG1 was associated with the poor prognosis of patients with PC. Furthermore, TUG1 knockdown significantly inhibited the proliferation and invasion of PC cells both in vitro and in vivo, while overexpression TUG1 promoted tumour cell proliferation, migration, and invasion. TUG1 directly targeted miR-29c, a tumour suppressor in several cancers. TUG1 knockdown significantly increased the expression of miR-29c and subsequently induced the downregulation of integrin subunit beta 1 (ITGB1), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9). The downregulation of miR-29c abolished the TUG1 knockdown-mediated inhibition of tumour growth in vitro and in vivo, whereas the upregulation of miR-29c enhanced the effects of TUG1 knockdown on PC cells. In conclusion, we demonstrate for the first time the oncogenic role of TUG1 in PC. The downregulation of TUG1 significantly inhibited the growth and migratory ability of PC cells in vitro and in vivo by targeting miR-29c. Our study provides a novel potential diagnostic biomarker and therapeutic target for PC.

Zhenbao Pill reduces Treg cell proportion in acute spinal cord injury rats by regulating TUG1/miR-214/HSP27 axis.

Background: Acute spinal cord injury (SCI) is one of the weakest pathologies that seriously affect the quality of life of patients. Objective: To study the mechanism of how Zhenbao Pill reduces Treg cell proportion and improves acute SCI. Methods: A rat SCI model was established. Flow cytometry analysis was performed to determine the Treg cell proportion. RNA immunoprecipitation (RIP) and RNA pull-down were applied in confirming taurine up-regulated gene 1 (TUG1) and miR-214 binding. Intrathecal injection of TUG1 siRNA was also conducted to determine the effect of TUG1 in vivo. Results: Zhenbao Pill promoted the expression of TUG1 and heat shock protein 27 (HSP27) protein, and reduced the expression of miR-214 and forkhead box protein p3 (Foxp3) as well as Treg cell proportion in a concentration-dependent manner in SCI rats or in vitro cultured CD4+ T cells. Knockdown of TUG1 reversed the high protein expression of HSP27 and the inhibition of Treg cell proportion as well as Foxp3 protein induced by Zhenbao Pill, and miR-214 inhibitor canceled the TUG1 knockdown effect. Further, miR-214 mimic reversed the inhibition of Treg cell proportion and Foxp3 protein expression by Zhenbao Pill, which was abolished by the overexpression of HSP27. The mechanism was validated in animal experiments. Conclusion: Zhenbao Pill regulated TUG1/miR-214/HSP27 signaling pathway to reduce Treg cell proportion and thus relieve acute SCI.

TUG1 promotes prostate cancer progression by acting as a ceRNA of miR-26a

Previous studies have demonstrated that taurine-upregulated gene 1 (TUG1) was aberrantly expressed and involved in multiple types of cancer; however, the expression profile and potential role of TUG1 in prostate cancer (PCa) remains unclear. The aim of the present study was to evaluate the expression and function of TUG1 in PCa. In the present study, we analyzed TUG1 expression levels of PCa patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown of TUG1 by RNAi was performed to explore its roles in cell proliferation, migration, and invasion. Here we report, for the first time, that TUG1 promotes tumor cell migration, invasion, and proliferation in PCa by working in key aspects of biological behaviors. TUG1 could negatively regulate the expression of miR-26a in PCa cells. The bioinformatics prediction revealed putative miR-26a-binding sites within TUG1 transcripts. In conclusion, our study suggests that long non-coding RNA (lncRNA) TUG1 acts as a functional oncogene in PCa development.

The lncRNA TUG1 promotes epithelial ovarian cancer cell proliferation and invasion via the WNT/β-catenin pathway.

PurposeEpithelial ovarian cancer (EOC) is among the most common malignant tumors of the endocrine system. Numerous studies have shown that genetic factors are important in the development of EOC, and there is evidence that long noncoding RNA molecules (lncRNAs) can regulate gene expression at the transcription, posttranscription, and epigenetic levels to influence cancer proliferation and invasion, cell differentiation, and apoptosis. However, the roles of lncRNAs in the pathogenesis of EOC remain unclear. Here, we investigated the role of the lncRNA, taurine upregulated gene 1 (TUG1), in EOC.Patients and methodsTUG1 mRNA levels were evaluated in EOC and matched normal tissue samples and in EOC cell lines by quantitative real-time PCR. Lentiviral vectors expressing the lncRNA, TUG1, and siRNA targeting TUG1 were constructed and transfected into EOC cells. MTT and Transwell assays were used to determine the effects of TUG1 on cell proliferation, migration, and invasion. Western blotting was performed to determine the influence of TUG1 up- or downregulation on WNT/β-catenin signaling, which is involved in the occurrence and development of cancer.ResultsTUG1 expression was clearly elevated in EOC compared with control tissue and cells. Moreover, TUG1 expression was associated with lymphatic metastasis, T stage, and clinical stage in patients with EOC. Downregulation of TUG1 in EOC inhibited cell proliferation, migration, and invasion. In EOC cells, levels of the WNT/β-catenin pathway factors, β-catenin, cyclin D1, and c-Myc, were significantly up- and downregulated in response to TUG1 over- and underexpression, respectively.ConclusionOur data suggest that knockdown of TUG1 may represent a novel therapeutic approach for the management of EOC.

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 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.

Long noncoding RNA TUG1 promotes cardiac fibroblast transformation to myofibroblasts via miR‑29c in chronic hypoxia.

Cardiac fibroblast‑myofibroblast transformation(FMT) contributes to the fibrotic deterioration evoked by chronic hypoxia. Growing evidence implicates long noncoding RNAs (lncRNAs) in various types of cardiac physiological and pathological processes, especially in cardiac fibrosis. In the present study, the lncRNA Taurine Upregulated Gene1(TUG1), reported as a regulator of hypoxia fibrosis in the lungs, was found to also be an important regulator of cardiac FMT. Specifically, the possible role of TUG1 in cardiac FMT and fibrosis under chronic hypoxia was investigated. It was revealed that the degree of fibrosis in heart tissues collected from congenital heart surgery patients with low pulse oxygen saturation and mice housed under chronic hypoxic and atmospheric pressure conditions was negatively correlated with pulse oxygen saturation. Moreover, TUG1 expression was positively correlated with the degree of fibrosis but negatively correlated with pulse oxygen saturation. Cardiac fibroblasts showed increased myofibroblast marker, collagen I and α‑SMA expression levels as the hypoxia time increased. TUG1 knockdown ameliorated the hypoxia‑induced FMT. A bioinformatics analysis predicted that TUG1 had miR‑29c binding sites in its 3'‑UTR and miR‑29c is a key regulator of cardiac fibrosis. The present study demonstrated that TUG1, along with miR‑29c, may contribute to cardiac FMT activation and promote fibrosis in chronic hypoxia.