Non-coding RNA TUG1 Research Articles

The role of LncRNA TUG1 in DNA damage and malignant transformation induced by Helicobacter pylori and N-methyl-N′-nitro-N-nitrosoguanidine on human esophageal epithelial cells

N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) and Helicobacter pylori might synergistically promote the malignant transformation of human esophageal epithelial cells (HEECs) through inducing DNA double-strand breaks (DSBs) and inhibition of PAXX protein expression. The long noncoding RNA (lncRNA) TUG1 is associated with multiple cancers, and its overexpression can promote cancer by interfering with the functions of oncogenes. LncRNA TUG1 is also associated with DNA methyltransferase 1 (DNMT1) and the epithelial signaling pathway of H. pylori infection. To explore the role of LncRNA TUG1 in the malignant transformation of HEECs induced by H.pylori + MNNG, a stable strain of HEECs with LncRNA TUG1 knockdown (LncRNA TUG1-KD) was constructed using RNA interference technology with lentivirus as a vector. Set up negative controls LncRNA TUG1-NC (null carrier lentivirus was selected to transfect HEECs) and block controls (normal HEECs without exposure). H. pylori + MNNG were added to the LncRNA TUG1-KD and LncRNA TUG1-NC groups for 6 h and then passaged until their malignant transformation. From each group, cells in the early, intermediate, and late stages of malignant transformation were used for the alkaline comet assay and determination of protein expression, including γ-H2AX and PAXX, by western blotting assay to assess DNA damage and repair processes. Clone formation assay in soft agar and nude mouse xenograft model was used to assess malignancy. This study suggests that H. pylori + MNNG promotes the malignant transformation of HEECs by inducing DNA DSBs and inhibiting PAXX expression, and this effect may be alleviated by LncRNA TUG1 knockdown. It elucidates the pathogenesis of EC from the perspective of the combined effect of epigenetic and environmental carcinogens, offering new insights for the comprehensive prevention and treatment of EC.

Expression level of long non-coding RNA MALAT1, GAS5, DANCR and TUG1 in peripheral blood leukocytes of patients with non-alcoholic fatty liver disease

Purpose: Comparative analysis of the expression level of long non-coding RNAs MALAT1, GAS5, DANCR, TUG1 in peripheral blood leukocytes (PBL) of healthy people and patients with NAFLD (liver steatosis, NASH of varying activity, liver cirrhosis). Materials and methods: We examined 106 patients diagnosed with NAFLD for the first time: 31 patients with liver steatosis (LS), 64 patients with weak (WA), moderate (MA) and high (HA) NASH activity and 11 patients at the stage of liver cirrhosis (LC). The control group consisted of 30 healthy donors. The mRNA level of the TUG1, DANCR, MALAT1, GAS5 genes in PBL was determined by RT-PCR. Results: A higher level of expression of the TUG1 gene was registered in the PBL of patients with NASH-WA compared to LS, and a tendency was revealed to increase the level of TUG1 mRNA in the PBL with increasing NASH activity, which indicates the possibility of using the level of TUG1 expression in the PBL as a minimally invasive diagnostic (to distinguish between LS and NASH-WA) and a prognostic marker (with the progression of NAFLD). Analysis of the expression level of lncRNA MALAT1 showed no significant differences between all studied groups. Results were obtained indicating complex dynamics of the GAS5 expression level: the level of transcripts increases during the formation of liver steatosis and then decreases during the transition to NASH. It was shown that the level of DANCR expression in the PBL of patients with NASH-WA is significantly lower than in patients with liver steatosis and NASH-MA. Conclusion: New data were obtained on the expression level of the MALAT1, GAS5, DANCR, TUG1 lncRNAs in the PBL of patients with NAFLD, indicating the possibility of using the level of TUG1 expression in the PBL as a minimally invasive diagnostic and prognostic marker in NAFLD. It has also been shown that the level of DANCR mRNA in PBL may have some diagnostic value in distinguishing between LS and NASH-WA.

Aerobic exercise suppresses cognitive injury in patients with Alzheimer’s disease by regulating long non-coding RNA TUG1

BackgroundAlzheimer’s disease (AD) is the primary reason for disability of the elderly. This article studied the diagnostic possibility of TUG1 and its potential mechanism in the regulation of aerobic exercise (AE) on AD. Methods77 AD patients undertook a three-month-long cycling exercise, and 77 healthy controls were recruited. Polymerase Chain Reaction amplification was applied to assess the expression of TUG1 and miR-129-5p. The diagnostic possibility was manifested by the receiver operating characteristic (ROC) curve. Spearman correlation analyzed the interrelationships between TUG1 and AD. In vivo, the APP/PS1 double transgenic mouse models of AD were included for rescue experiments. Morris water maze (MWM) was performed to assess cognitive function of AD mice. ResultsThe content of TUG1 was ascended in AD patients and was diminished after AE. The increase of TUG1 indicated the high risk of the occurrence of AD. TUG1 was closely connected to the cognitive assessment tools of AD patients. The TUG1/ miR-129-5p axis was the regulator of the regulation of AE in AD mice. ConclusionTUG1 was involved in AD development and targeted miR-129-5p to participate in the regulation of AE.

Retraction: Long noncoding RNA TUG1 is a diagnostic factor in lung adenocarcinoma and suppresses apoptosis via epigenetic silencing of BAX.

Retraction: Long noncoding RNA TUG1 is a diagnostic factor in lung adenocarcinoma and suppresses apoptosis via epigenetic silencing of BAX.

Retracted: Long Noncoding RNA TUG1 Aggravates Cerebral Ischemia/Reperfusion Injury by Acting as a ceRNA for miR-3072-3p to Target St8sia2.

[This retracts the article DOI: 10.1155/2022/9381203.].

Зміни експресії довгих некодуючих РНК H19, TUG1, GAS5, MIAT при ішемії-реперфузії міокарда

Long non-coding RNAs (lncRNAs) are the most numerous group of transcripts performing various functions, including the development of cardiovascular pathologies. We investigated the changes in expression of four long non-coding RNAs (H19, TUG1, GAS5, MIAT) under conditions of anoxia-reoxygenation in neonatal rat cardiomyocyte culture and ischemia-reperfusion in adult Wistar rats. A significant decrease in the expression of all four long non-coding RNAs in cell culture under experimental conditions was established. The regime of prolonged anoxia-reoxygenation led to a sharp increase in the expression level of long non-coding RNA MIAT by twice, but compared to normoxia, these changes were not significant. After ischemia-reperfusion in rat myocardium, the content of long non-coding RNA TUG1 increased by 22 times, while the expression of H19 decreased by 3.79 times, and in rat plasma, the expression of long non-coding RNA MIAT increased by 3.79 times. The obtained results allow considering long non-coding RNAs H19 and TUG1 as potential targets in ischemic myocardial injury, and MIAT as a biomarker of cardiovascular pathologies.

Long Non-Coding RNA TUG1 Gene Polymorphism and TUG1 Expression Level as Molecular Biomarkers of Systemic Lupus Erythematosus and Lupus Nephritis.

Long non-coding RNA (lncRNA) TUG1 acts as a proto-oncogene, allowing the proliferation of tumor cells, and it has been related to inflammation. Therefore, we aimed in this study to investigate for the first time the role of TUG1 gene polymorphism and the TUG1 level as biomarkers in systemic lupus erythematosus (SLE) and their link to lupus nephritis 145 SLE. A total of 145 healthy controls were subjected to clinical and laboratory evaluation. The disease activity was assessed by the SLE disease activity index (SLEDAI) score. SLE patients were divided into two subgroups according to the presence of lupus nephritis. The TUG1 gene polymorphisms rs5749201 and rs886471 were determined by Sanger sequencing, and TUG1 expression was assessed by qRT-PCR. There was a significant increase in the risk of SLE AA, TA, dominant genotypes, and the A allele of rs5749201 (p < 0.001) by 4.9-, 10.1-, 6.5-, and 2.5-fold in comparison to the relative control. GG and TG, dominant genotypes and the G allele of rs886471 (p < 0.01) increased the risk by 5.09-, 11.9-, 6.5-, and 2.6-fold. AA, A allele, dominant and recessive rs5749201genotypes increased the risk of lupus nephritis by 16.6-, 7.4-, 7.1-, and 12.2-fold, respectively (p < 0.05). GG, dominant and recessive genotypes, and the G allele of rs886471 increased the risk of lupus nephritis by 17.04-, 7.8-, 9.4-, and 6.08-fold, respectively (p < 0.05). Additionally, the AG haplotype increased the risk of SLE and lupus nephritis by 2.7- and 7.8-fold, respectively. The AA rs5749201 and GG rs886471 variants are significantly associated with more severe disease (p < 0.001). TUG1 expression was significantly higher in SLE than in the control and in the lupus nephritis than in non-lupus nephritis cases (p < 0.05). Interestingly, AA rs5749201 and GG rs886471 were significantly associated with higher TUG1 levels (p < 0.001). It was also found that AA rs5749201 and high SLEDAI were predictors of lupus nephritis. Overall, our findings illustrated for the first time that TUG1 gene rs5749201 and rs886471 variants were associated with increased risk of SLE, more severe disease, and lupus nephritis, and the TUG1 level could be used as a diagnostic biomarker of SLE and lupus nephritis.

LncRNA Tug1 relieves the steatosis of SelenoF-knockout hepatocytes via sponging miR-1934-3p.

Metabolic dysfunction associated with fatty liver disease (MAFLD), always accompanied by disturbance of glucose and lipid metabolism, is becoming the most difficult obstacle in the next decades. In the current research, we uncover that the potent non-coding RNA Tug1, which is related to metabolic enzymes, regulates hepatocytes steatosis induced by sodium palmitate via miR-1934-3p absorbing. The knockdown of lncRNA-Tug1 distinctly rescues the increased expression level of glycolytic enzymes and fatty acid synthetase via releasing more mature miR-1934-3p in hepatocytes. Moreover, miR-1934-3p suppresses Selenoprotein F (SelenoF) through binding with the SelenoF 3'UTR effectors; importantly, we demonstrated that the deletion of SelenoF consistent with the lncRNA-Tug1's effecting on metabolism enzymes. In the current paper, the interaction of Tug1/miR-1934-3p/SelenoF was verified by the dual-luciferase reporter system, and IRS1/AKT pathway possesses the essential role in glucolipid metabolism when SelenoF is deleted. We concluded that lncRNA Tug1 functioned as ceRNA to alleviate steatosis and glycolysis in hepatocytes of C57BL/6 through adsorbing miR-1934-3p to release SelenoF and triggering IRS/AKT pathway. The Tug1/miR-1934-3p/SelenoF constructed the ceRNA interact network Selenoprotein F accelerates glucolipid metabolism via IRS1/AKT pathway SelenoF-/- alleviates steatosis in mice liver.

Study of Long Non-Coding RNA Tug1 Expression in Egyptian Colorectal Adenocarcinoma Patients

Abstract Purpose Colorectal cancer (CRC) is one of the most fatal tumors worldwide. In Egypt, most CRC cases occur in individuals &gt; 40 years old. TUG1 has been proved to be disrupted in different malignancies and may have a critical role in tumor progression, invasion, and metastasis. However, its role in CRC has not been adequately studied. Materials / Methods Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression levels of long non-coding RNA (LncRNA) taurine upregulated gene 1 (TUG1), in nonmetastatic and metastatic CRC tissues and adjacent noncancerous tissues as control. Results LncRNA TUG1 expression was significantly upregulated in both nonmetastatic and metastatic CRC tissues, in comparison with the adjacent noncancerous tissue. It was found that TUG1 could have a possible prognostic role in CRC, by comparing the sensitivity and specificity of TUG1 with those of CEA and CA19–9. Conclusion The results of the current study suggest that the LncRNA TUG1 participates in the malignant behaviors of CRC cells.

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

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

Long noncoding RNA TUG1 regulates smooth muscle cell differentiation via KLF4-myocardin axis.

Abdominal aortic aneurysms (AAAs) are asymptomatic vascular diseases that have life-threatening outcomes. Smooth muscle cell (SMC) dysfunction plays an important role in AAA development. The contribution of non-coding genome, specifically the role of long non-coding RNAs (lncRNAs) in SMC dysfunction, is relatively unexplored. We investigated the role of lncRNA TUG1 in SMC dysfunction. To identify potential lncRNAs relevant to SMC functionality, lncRNA profiling was performed in angiotensin-II-treated SMCs. AAA was induced by angiotensin-II treatment in mice. Transcriptional regulation of TUG1 was studied using promoter luciferase and chromatin-immuno-precipitation experiments. Gain-or-loss-of-function experiments were performed in vitro to investigate TUG1-mediated regulation of SMC function. Immunoprecipitation experiments were conducted to elucidate the mechanism underlying TUG1-mediated SMC dysfunction. TUG1 was upregulated in SMCs following angiotensin-II treatment. Similarly, TUG1 levels were elevated in abdominal aorta in a mouse model of angiotensin-II-induced AAA. Further investigations showed that angiotensin-II-induced TUG1 expression could be suppressed by inhibiting Notch-signaling pathway, both in vitro and in mouse AAA model and that TUG1 is a direct transcriptional target of the Notch pathway. In aneurysmal tissues, TUG1 expression was inversely correlated with the expression of SMC contractile genes. Overexpression of TUG1 repressed SMC differentiation in vitro, whereas siRNA/shRNA-mediated TUG1 knockdown showed an opposite effect. Mechanistically, TUG1 interacts with transcriptional repressor KLF4 and facilitates its recruitment to myocardin promoter ultimately leading to the repression of SMC differentiation. In summary, our study uncovers a novel role for the lncRNA TUG1 wherein it modulates SMC differentiation via the KLF4-myocardin axis, which may have potential implications in AAA development.NEW & NOTEWORTHY TUG1 is an angiotensin-II-induced long noncoding RNA that mediates smooth muscle cell (SMC) dysfunction through interaction with transcriptional repressor KLF4.

Retraction Note: Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal.

The article "Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal", by K. Zhao, J.-Y. Tan, Q.-D. Mao, K.-Y. Ren, B.-G. He, C.-P. Zhang, L.-Z. Wei published in Eur Rev Med Pharmacol Sci 2019; 23 (1): 312-320-DOI: 10.26355/eurrev_201901_16778-PMID: 30657572 has been retracted by the authors for the following reasons: We are still conducting research in the effect of long non-codingRNA TUG1 in interstitial cells of Cajal recently. It turned out that some of the current experimental results are inconsistent with the previous results. Some data cannot be repeated by further research. We need to further confirm the effect of long non-coding RNA TUG1 on alleviating TNF-α-induced inflammatory injury in interstitial cells of Cajal and for this reason, the authors all agreed to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16778.

The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis

sBackgroundLong-stranded non-coding RNA TUG1 is lowly expressed in osteoarthritic chondrocytes. This study aimed to elucidate the role of TUG1 in osteoarthritic cartilage damage and the underlying mechanisms.MethodsCombined database analysis, using primary chondrocytes as well as the C28/I2 cell line, was performed by qRT-PCR, Western blotting, and immunofluorescence to determine the expression of TUG1, miR-144-3p, DUSP1, and other target proteins. Dual luciferase reporter gene and RIP to verify direct interaction of TUG1 with miR-144–3-p and miR-144–3-p with DUSP1, Annexin V-FITC/PI double staining to detect apoptosis. CCK-8 to detect cell proliferation. The biological significance of TUG1, miR-144-3p, and DUSP1 was assessed in vitro experiments using siRNA for TUG1, mimic and repressor for miR-144-3p, and overexpression plasmid for DUSP1. In this study, all data were subjected to a t-test or one-way analysis of variance with a p-value < 0.05 as the cutoff.ResultsTUG1 expression was closely associated with osteoarthritic chondrocyte damage, and knockdown of TUG1 significantly promoted chondrocyte apoptosis and inflammation. In the present study, we found that TUG1 inhibited chondrocyte apoptosis and inflammation by competitively binding miR-144-3p, deregulating the negative regulatory effect of miR-144-3p on DUSP1, promoting DUSP1 expression, and inhibiting the p38 MAPK signaling pathway.ConclusionsIn conclusion, our study clarifies the role of the ceRNA regulatory network of TUG1/miR-144-3p/DUSP1/P38 MAPK in OA cartilage injury and provides an experimental and theoretical basis for genetic engineering tools to promote articular cartilage repair.Graphical abstract

Long noncoding RNA TUG1 promotes proliferation, migration and cisplatin resistance in oral squamous cell carcinoma.

Long noncoding RNA TUG1 promotes proliferation, migration and cisplatin resistance in oral squamous cell carcinoma.

LncRNA TUG1 relieves renal mesangial cell injury by modulating the miR-153-3p/Bcl-2 axis in lupus nephritis.

Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus. Our experiments aimed to evaluate the molecular mechanisms of long noncoding RNA (lncRNA) TUG1 in a human renal mesangial cell (HRMC) model of LN. Cells were treated with lipopolysaccharide (LPS) to induce inflammatory damage. StarBase, TargetScan, and a luciferase reporter assay were used to predict and confirm the interactions between lncRNA TUG1, miR-153-3p, and Bcl-2. We determined the lncRNA TUG1 and miR-153-3p levels in LPS-induced HRMCs using quantitative reverse transcription PCR (RT-qPCR). MTT and flow cytometry analyses were used to detect HRMC proliferation and apoptosis, respectively. In addition, the expression of the apoptosis-related proteins Bax and Bcl-2 was evaluated using western blot analysis and RT-qPCR. Lastly, the secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) was assessed using ELISA. miR-153-3p directly targeted lncRNA TUG1. The level of lncRNA TUG1 was remarkably lower and miR-153-3p expression was markedly higher in LPS-treated HRMCs than in untreated cells. Transfection with TUG1-plasmid relieved LPS-induced HRMC injury, as evidenced by increased cell viability, inhibited apoptotic cells, reduced Bax expression, increased Bcl-2 level, and reduced secretion of inflammatory cytokines. Importantly, these findings were reversed by miR-153-3p mimic. We also found that miR-153-3p directly targeted Bcl-2 and negatively regulated Bcl-2 expression in HRMCs. In addition, our findings suggest that miR-153-3p inhibitor relieved LPS-induced HRMC injury via the upregulation of Bcl-2. lncRNA TUG1 alleviated LPS-induced HRMC injury through regulation of the miR-153-3p/Bcl-2 axis in LN.

Overexpression of lncRNA TUG1 enhances the efficacy of DC-CIK immunotherapy in neuroblastoma in vitro and in vivo.

Long non-coding RNA (LncRNA) TUG1 plays a critical role in the development of human cancers. This study explored whether TUG1 is involved in the cytotoxicity of dendritic cells and cytokine-induced killer cells (DCs-CIK), an immunotherapy approach, in neuroblastoma. A TUG1 expression plasmid was transfected into DCs. Neuroblastoma SK-N-SH cells were incubated with CIK cells, DCs-CIK cells, and TUG1-overexpressing DCs-CIK cells, with or without irradiation. SK-N-SH cell viability, colony formation, migration, and apoptosis were analyzed using CCK-8, colony formation assay, transwell assay, and flow cytometry, respectively. Production of IL-12, IL-2 and IFN-γ in the supernatants was determined using ELISA. A dual luciferase activity assay was performed to confirm the molecular interactions between TUG1 and miR-204. Tumor-bearing mice were established by injection of SK-N-SH cells followed by stimulation with CIK cells, DC-CIK cells, and TUG1-overexpressing DCs-CIK cells. Compared to CIK alone or DC-CIK therapy, overexpression of TUG1 significantly suppressed tumor cell proliferation, colony formation, and migration of neuroblastoma cells. Moreover, upregulation of TUG1 robustly induced apoptosis and altered key molecules associated with apoptosis and epithelial-mesenchymal transition. Contents of IL-12, IL-2 and IFN-γ were dramatically elevated in the supernatants in the coculturing system upon transfection with TUG1. In addition, TUG1 was found to be act as miR-204 sponge. Furthermore, in vivo experiments demonstrated that upregulation of TUG1 potentiated the antitumor activity of DC-CIK immunotherapy. Overexpression of TUG1 promotes DC maturation and enhances CIK cytotoxicity, suggesting that TUG1 may be a novel target for enhancing DC-CIK based immunotherapy for neuroblastoma.

Retraction Note: Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma.

Retraction Note: Downregulation of long non-coding RNA TUG1 suppresses tumor growth by promoting ubiquitination of MET in diffuse large B-cell lymphoma.

TUG1/MAZ/FTH1 Axis Attenuates the Antiglioma Effect of Dihydroartemisinin by Inhibiting Ferroptosis.

Glioma is the most common primary intracranial malignant tumor in the brain. Currently, due to the limited treatment methods, the clinical outcome of patients with standard surgery combined with radiotherapy and chemotherapy is not satisfactory. Therefore, we urgently need to develop effective drugs to solve this problem. As a semisynthetic derivative of artemisinin, dihydroartemisinin (DHA) has been proved to have antitumor activity in glioma, which can induce apoptosis and inhibit the proliferation, migration, and invasion of glioma cells. In recent years, ferroptosis has been identified as another antitumor mechanism of DHA. Researchers have shown that DHA could promote ferroptosis in glioma cells. However, the specific molecular mechanisms of ferroptosis induced by DHA need more exploration. In this study, we found DHA could induce ferroptosis with ROS production and lipid peroxidation in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. Surprisingly, we found FTH1, a negative regulator of ferroptosis, upregulated in DHA treated glioma cells. It indicated that there should be some mechanisms that may cause ferroptosis attenuation in DHA treated glioma cells. For the first time, we confirmed that MYC-associated zinc finger protein (MAZ) could actively regulate FTH1 by binding to FTH1 promoter by CHIP assay. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.

Diagnostic and Prognostic Value of Deregulated Circulating Long Non-coding RNA TUG1 in Elderly Patients with Severe Pneumonia.

To investigate the expression pattern of long non-coding RNA TUG1 in elderly patients with severe community-acquired pneumonia (sCAP) and evaluate its diagnostic and prognostic value for sCAP. Serum TUG1 levels were detected in 130 sCAP patients and 122 healthy volunteers via qRT-PCR method. The receiver operating characteristic (ROC) curve and k-M plot were drawn for the diagnostic and prognostic value evaluation. A diminished trend of TUG1 was detected in the serum of sCAP cases, and negatively correlated with the concentration of TNF-α, CRP, suPAR and sTREM-1. Among the 130 cases, 30 cases died from sCAP within 30days after admission. Serum TUG1 had the diagnostic value for 30-day mortality prediction with the AUC of 0.823. In the non-survival group, more cases had old age, high CURB score and PSI score. K-M plot demonstrated that cases with low TUG1 levels showed poor survival than those carrying high TUG1 levels. Serum TUG1 was an independent risk factor for death in elderly patients with sCAP within 30days after admission. Serum TUG1 was at low expression in sCAP patients, and it had the predictive value for the clinical prognosis of elderly sCAP patients.

Long non-coding RNA Tug1 modulates mitochondrial and myogenic responses to exercise in skeletal muscle

BackgroundMitochondria have an essential role in regulating metabolism and integrate environmental and physiological signals to affect processes such as cellular bioenergetics and response to stress. In the metabolically active skeletal muscle, mitochondrial biogenesis is one important component contributing to a broad set of mitochondrial adaptations occurring in response to signals, which converge on the biogenesis transcriptional regulator peroxisome proliferator-activated receptor coactivator 1-alpha (PGC-1α), and is central to the beneficial effects of exercise in skeletal muscle. We investigated the role of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1), which interacts with PGC-1α in regulating transcriptional responses to exercise in skeletal muscle.ResultsIn human skeletal muscle, TUG1 gene expression was upregulated post-exercise and was also positively correlated with the increase in PGC-1α gene expression (PPARGC1A). Tug1 knockdown (KD) in differentiating mouse myotubes led to decreased Ppargc1a gene expression, impaired mitochondrial respiration and morphology, and enhanced myosin heavy chain slow isoform protein expression. In response to a Ca2+-mediated stimulus, Tug1 KD prevented an increase in Ppargc1a expression. RNA sequencing revealed that Tug1 KD impacted mitochondrial Ca2+ transport genes and several downstream PGC-1α targets. Finally, Tug1 KD modulated the expression of ~300 genes that were upregulated in response to an in vitro model of exercise in myotubes, including genes involved in regulating myogenesis.ConclusionsWe found that TUG1 is upregulated in human skeletal muscle after a single session of exercise, and mechanistically, Tug1 regulates transcriptional networks associated with mitochondrial calcium handling, muscle differentiation and myogenesis. These data demonstrate that lncRNA Tug1 exerts regulation over fundamental aspects of skeletal muscle biology and response to exercise stimuli.