Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

The role of EZH2 and its regulatory lncRNAs as a serum-based biomarker in Alzheimer's disease.

BACKGROUND: Long noncoding RNAs (lncRNAs) have become a hot topic in the human nervous system. Moreover, circulating lncRNAs have been suggested as possible biomarkers for central nervous system processes and neurodegenerative diseases. The present research aimed to highlight the role of plasma lncRNAs TUG1, FEZF1-AS1, and EZH2 gene as diagnostic biomarkers in Alzheimer's disease (AD). METHODS: Plasma samples for the study were provided by 100 AD patients and 100 matched controls. Real-time quantitative reverse transcriptase PCR was used to determine the plasma level of the aforementioned lncRNAs. Furthermore, the plasma level of EZH2 protein in the participants' blood was determined using the ELISA technique. RESULTS: In contrast to controls, down-regulation of the EZH2 gene and protein was reported in the plasma of patients with AD. Additionally, plasma samples from AD patients showed up-and-down-regulation of the lncRNAs TUG1 and FEZF1-AS1, respectively. CONCLUSION: Our new findings suggest that the EZH2 gene, plasma lncRNA TUG1, and FEZF1-AS1 may contribute, as valuable biomarkers, to AD diagnosis.

ANRIL, H19 and TUG1: a review about critical long non-coding RNAs in cardiovascular diseases.

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.

Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1.

The epigenetic regulation of lncRNA TUG1 has garnered significant attention in the context of diabetes and its associated disorders. TUG1's multifaceted roles in gene expression modulation, and cellular differentiation, and it plays a major role in the growth of diabetes and the issues that are related to it due to pathological processes. In diabetes, aberrant epigenetic modifications can lead to dysregulation of TUG1 expression, contributing to disrupted insulin signaling, impaired glucose metabolism, and beta-cell dysfunction. Moreover, it has been reported that TUG1 contributes to the development of problems linked to diabetes, such as nephropathy, retinopathy, and cardiovascular complications, through epigenetically mediated mechanisms. Understanding the epigenetic regulations of TUG1 offers novel insights into the primary molecular mechanisms of diabetes and provides a possible path for healing interventions. Targeting epigenetic modifications associated with TUG1 holds promise for restoring proper gene expression patterns, ameliorating insulin sensitivity, and mitigating the inception and development of diabetic associative diseases. This review highlights the intricate epigenetic landscape that governs TUG1 expression in diabetes, encompassing DNA methylation and alterations in histone structure, as well as microRNA interactions.

LncRNA TUG1 and its Molecular Mechanisms in Human Cancer.

As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies.

Long non-coding RNA TUG1 is downregulated in Friedreich's ataxia.

Friedreich's ataxia is a neurodegenerative disorder caused by reduced frataxin levels. It leads to motor and sensory impairments and has a median life expectancy of around 35 years. As the most common inherited form of ataxia, Friedreich's ataxia lacks reliable, non-invasive biomarkers, prolonging and inflating the cost of clinical trials. This study proposes TUG1, a long non-coding RNA, as a promising blood-based biomarker for Friedreich's ataxia, which is known to regulate various cellular processes. In a previous study using a frataxin knockdown mouse model, we observed several hallmark Friedreich's ataxia symptoms. Building on this, we hypothesized that a dual-source approach-comparing the data from peripheral blood samples from Friedreich's ataxia patients with tissue samples from affected areas in Friedreich's ataxia knockdown mice, tissues usually unattainable from patients-would effectively identify robust biomarkers. A comprehensive reanalysis was conducted on gene expression data from 183 age- and sex-matched peripheral blood samples of Friedreich's ataxia patients, carriers and controls and 192 tissue data sets from Friedreich's ataxia knockdown mice. Blood and tissue samples underwent RNA isolation and quantitative reverse transcription polymerase chain reaction, and frataxin knockdown was confirmed through enzyme-linked immunosorbent assays. Tug1 RNA interaction was explored via RNA pull-down assays. Validation was performed in serum samples on an independent set of 45 controls and 45 Friedreich's ataxia patients and in blood samples from 66 heterozygous carriers and 72 Friedreich's ataxia patients. Tug1 and Slc40a1 emerged as potential blood-based biomarkers, confirmed in the Friedreich's ataxia knockdown mouse model (one-way ANOVA, P ≤ 0.05). Tug1 was consistently downregulated after Fxn knockdown and correlated strongly with Fxn levels (R 2 = 0.71 during depletion, R 2 = 0.74 during rescue). Slc40a1 showed a similar but tissue-specific pattern. Further validation of Tug1's downstream targets strengthened its biomarker candidacy. In additional human samples, TUG1 levels were significantly downregulated in both whole blood and serum of Friedreich's ataxia patients compared with controls (Wilcoxon signed-rank test, P < 0.05). Regression analyses revealed a negative correlation between TUG1 fold-change and disease onset (P < 0.0037) and positive correlations with disease duration and functional disability stage score (P < 0.04). This suggests that elevated TUG1 levels correlate with earlier onset and more severe cases. This study identifies TUG1 as a potential blood-based biomarker for Friedreich's ataxia, showing consistent expression variance in human and mouse tissues related to disease severity and key Friedreich's ataxia pathways. It correlates with frataxin levels, indicating its promise as an early, non-invasive marker. TUG1 holds potential for Friedreich's ataxia monitoring and therapeutic development, meriting additional research.

LncRNA TUG1 mediates microglial inflammatory activation by regulating glucose metabolic reprogramming.

Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1ß (IL-1ß), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.

Suppression of the lncRNA TUG1 alleviates neuropathic pain in rats with chronic contractile injury via the miR-29b-3p/HMGB1 axis.

INTRODUCTION: The present research focused on the function of lncRNA taurine upregulated 1 (TUG1) in a rat neuropathic pain (NP) model constructed by chronic contractile injury (CCI). MATERIAL AND METHODS: Construction of the NP rat model was performed by CCI surgery. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were applied to examine the NP behavior. RT-qPCR was established to explore the levels of TUG1, microRNA (miR)-29b-3p, and HMGB1. ELISA was carried out to evaluate the concentrations of interleukin (IL)-6, IL-1ß, tumor necrosis factor α (TNF-α), IL-4, and IL-6. The underlying mechanisms of TUG1 were explored by RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter (DLR) assay. RESULTS: TUG1 and HMGB1 were statistically elevated in the tissue of CCI rats, while miR-29b-3p was reduced. TUG1 competitively binds to miR-29b-3p to upregulate HMGB1 levels. Suppression of TUG1 persistently decreased PWL and PWT along with increased frequency of paw-lifting, whereas this alleviation was typically rescued by the abrogated miR-29b-3p. Analogously, knockdown of TUG1 inhibited CCI-induced overproduction of IL-6, IL-1ß, and TNF-α, and reduction of IL-4 and IL-6, but this inhibition was partially abrogated by the reduction of miR-29b-3p. CONCLUSIONS: Suppression TUG1 can alleviate NP hypersensitivity and neuroinflammation in CCI rats by competitively binding miR-29b-3p to weaken HMGB1.

Androgen receptor deficiency-induced TUG1 in suppressing ferroptosis to promote benign prostatic hyperplasia through the miR-188-3p/GPX4 signal pathway.

Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of the prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, a cell death mechanism triggered by iron-dependent lipid peroxidation and closely linked to inflammation, has yet to be fully understood in the context of BPH. Using RNA sequencing, we observed a significant elevation of taurine-upregulated gene 1 (TUG1) long noncoding RNA (lncRNA) in BPH tissues compared to normal prostate tissue. High levels of TUG1 exhibited a discernible correlation with both prostate volume and the extent of inflammatory infiltration in BPH patients. The suppression of TUG1 not only led to a reduction in prostate size but also ameliorated AR-deficiency-induced prostatic hyperplasia. Mechanistically, a decrease in AR in prostate luminal cells prompted macrophage aggregation and the release of IL-1ß, subsequently fostering the transcription of TUG1 via MYC. Induced TUG1, through competitive binding with miR-188-3p, facilitated the expression of GPX4, thereby diminishing intracellular ROS levels and impeding ferroptosis in prostate luminal cells. Notably, the ferroptosis inducer JKE-1674 alleviated inflammation-induced prostatic hyperplasia in vivo. Together, these findings suggest that AR deficiency crucially inhibits ferroptosis, promoting BPH via the TUG1/miR-188-3p/GPX4 signaling axis, and making ferroptosis induction a promising therapeutic strategy for BPH patients with AR deficiency.

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

BACKGROUND: Alzheimer'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. METHODS: 77 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. RESULTS: The 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. CONCLUSION: TUG1 was involved in AD development and targeted miR-129-5p to participate in the regulation of AE.

The transcript level of long non-coding RNAs; MALAT1 and TUG1, and the association with metabolic syndrome-related parameters in women with overweight and obesity.

Background: Recent studies have addressed the possible role of long non-coding RNAs (lnc-RNAs), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and Taurine Upregulated Gene 1 (TUG1), in modulating the underlying mechanisms of obesity-related metabolic abnormalities. However, studies are limited and contradictory. Hence, we sought to investigate the relationship of the transcript level of these two lnc-RNAs with metabolic syndrome (MetS)-related parameters in women with obesity and overweight. Method: This cross-sectional study was conducted on 342 women with obese and overweight. We conducted assessments encompassing anthropometric measurements, body composition analysis, fasting blood sugar (FBS) levels, lipid profile analysis, insulin levels, HOMA-IR index, and liver enzyme profiling. A quantitative real-time polymerase chain reaction (PCR) was used to evaluate transcript levels of MALAT1 and TUG1. Also, a 147-question semi-quantitative food frequency questionnaire (FFQ) and the International Physical Activity Questionnaire (IPAQ) were used to evaluate food intake and physical activity, respectively. Results: There was a significant association between FBS and MALAT1 transcript level (ß: 0.382; 95% CI: 0.124, 0.640; P = 0.004). Also, there was a significant association between triglyceride (TG) and MALAT1 transcript level (ß: 4.767; 95% CI: 2.803, 6.731; P < 0.0001). After adjusting for age, BMI, energy intake, and physical activity, an inverse significant association was observed between high-density lipoprotein cholesterol (HDL-c) and MALAT1 transcript level (ß: -0.325; 95% CI: -0.644, -0.006; P = 0.046). Conclusions: Our findings indicated positive associations between mRNA levels of MALAT1 and MetS-related parameters, including FBG, TG, HDL, and systolic blood pressure in overweight and obese women. However, large prospective studies are needed to further establish this concept. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01367-2.

LncRNA taurine upregulated gene 1 in liver disease.

Long non-coding RNAs (lncRNAs) are RNA sequences exceeding 200 nucleotides in length that lack protein-coding capacity and participate in diverse biological processes in the human body, particularly exerting a pivotal role in disease surveillance, diagnosis, and progression. Taurine upregulated gene 1 (TUG1) is a versatile lncRNA, and recent studies have revealed that the aberrant expression or function of TUG1 is intricately linked to the pathogenesis of liver diseases. Consequently, we have summarized the current understanding of the mechanism of TUG1 in liver diseases such as liver fibrosis, fatty liver, cirrhosis, liver injury, hepatitis, and liver cancer. Moreover, mounting evidence suggests that interventions targeting TUG1 or its downstream pathways may hold therapeutic promise for liver diseases. This review elucidates the characteristics, mechanisms, and targets of TUG1 in liver diseases, offering a theoretical basis for the prevention, diagnosis, treatment, and prognostic biomarkers of liver diseases.

The role of LncRNA TUG1 in DNA damage and repair 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.

M6A-mediated upregulation of lncRNA TUG1 in liver cancer cells regulates the antitumor response of CD8+ T cells and phagocytosis of macrophages.

Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3-mediated m6A modification led to TUG1 upregulation is demonstrated. Knockdown of TUG1 inhibited tumor growth and metastasis, increased the infiltration of CD8+ T cells and M1-like macrophages in tumors, promoted the activation of CD8+ T cells through PD-L1, and improved the phagocytosis of macrophages through CD47. Mechanistically, TUG1 regulated PD-L1 and CD47 expressions by acting as a sponge of miR-141 and miR-340, respectively. Meanwhile, TUG1 interacted with YBX1 to facilitate the upregulation of PD-L1 and CD47 transcriptionally, which ultimately regulated tumor immune evasion. Clinically, TUG1 positively correlated with PD-L1 and CD47 in HCC tissues. Moreover, the combination of Tug1-siRNA therapy with a Pdl1 antibody effectively suppressed tumor growth. Therefore, the mechanism of TUG1 in regulating tumor immune evasion is revealed and can inform existing strategies targeting TUG1 for enhancing HCC immune therapy and drug development.

Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.

Background: Klotho deficiency is a common feature of premature aging and chronic kidney disease (CKD). As such, restoring Klotho expression could be a logic strategy for protecting against various nephropathies. In this study, we demonstrate that KP1, a Klotho-derived peptide, inhibits cellular senescence by restoring endogenous Klotho expression. Methods: The effects of KP1 on cellular senescence and Klotho expression were assessed in mouse models of CKD. RNA-sequencing was employed to identify the microRNA involved in regulating Klotho by KP1. Gain- or loss-of-function approaches were used to assess the role of miR-223-3p and IncRNA-TUG1 in regulating Klotho and cellular senescence. Results: KP1 inhibited senescence markers p21, p16 and γ-H2AX in tubular epithelial cells of diseased kidneys, which was associated with its restoration of Klotho expression at the posttranscriptional level. Profiling of kidney microRNAs by RNA sequencing identified miR-223-3p that bound to Klotho mRNA and inhibited its protein expression. Overexpression of miR-223-3p inhibited Klotho and induced p21, p16 and γ-H2AX, which were negated by KP1. Conversely, inhibition of miR-223-3p restored Klotho expression, inhibited cellular senescence. Furthermore, miR-223-3p interacted with lncRNA-TUG1 and inhibited its expression. Knockdown of lncRNA-TUG1 increased miR-223-3p, aggravated Klotho loss and worsened cellular senescence, whereas KP1 mitigated all these changes. Conclusion: These studies demonstrate that KP1 inhibits cellular senescence and induces Klotho expression via posttranscriptional regulation mediated by miR-223-3p and lncRNA-TUG1. By restoring endogenous Klotho, KP1 elicits a broad spectrum of protective actions and could serve as a promising therapeutic agent for fibrotic kidney disorders.

lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

Study of long non-coding RNA Tug 1 expression in Egyptian colorectal adenocarcinoma patients

Purpose: Colorectal cancer (CRC) is one of the most fatal tumors worldwide. In Egypt, most CRC cases occur in individuals > 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. (AU)

lncRNA TUG1 promotes proliferation and differentiation of osteoblasts by regulating the miR-545-3p/CNR2 axis

Osteoblast differentiation is an effective way to promote bone formation. Long non-coding RNA taurine upregulated 1 (TUG1) has been identified as a crucial modulator of multiple biological processes. This study was designed to investigate the function of TUG1 in the proliferation and differentiation of osteoblast precursor cells hFOB1.19. In this study, we found that TUG1 promoted hFOB1.19 cell proliferation, while TUG1 knockdown hindered cell proliferation. TUG1 and cannabinoid receptor 2 (CNR2) were upregulated, while miR-545-3p was down-regulated in hFOB1.19 cells undergoing osteoblastic differentiation. TUG1 induced osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and the expression of osteoblastic differentiation markers. TUG1 was a sponge of miR-545-3p and regulated osteoblastic differentiation by modulating miR-545-3p. Moreover, miR-545-3p directly targeted CNR2 and restored the effect of CNR2 on osteoblastic differentiation. In conclusion, TUG1 accelerated the proliferation and differentiation of osteoblasts by sponging miR-545-3p and increasing CNR2 expression, which might provide a new biomarker for bone diseases.

Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascular cognitive impairment

OBJECTIVES: Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. METHODS: The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. RESULTS: The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. CONCLUSIONS: The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.