RESUMEN

Long non-coding RNAs (LncRNAs) play a substantial role in the process of cerebral ischemia-reperfusion injury (CIRI). The present work aimed to determine the probable mechanism by which LncRNA TUG1 exacerbates CIRI via the miR-340-5p/phosphatase and tensin homolog (PTEN) pathway. After developing a middle cerebral artery occlusion/reperfusion (MCAO/R) model, pcDNA-TUG1 together with miR-340-5p agomir were administrated in vivo. Furthermore, the neurologic defects in rats were assessed by a modified neurological severity score. Moreover, 2,3,5-Triphenyl-2 H-tetrazolium chloride stain-step was performed to determine the brain's infarct size. In addition, western blotting, immunohistochemistry, and qRT-PCR experiments were utilized for gauging the proteomic/genomic expression-profiles. Luciferase reporter assay validated correlations across TUG1, miR-340-5p, together with PTEN. The results indicated relatively reduced miR-340-5p levels in MCAO/R models, while upregulated TUG1 levels. The pcDNA-TUG1-treated rats indicated increasing neurological dysfunction, whereas the miR-340-5p agomir-treated rats showed improvement. Furthermore, miR-340-5p was determined to be the expected and confirmed TUG1 target. All things considered, the findings suggested that PTEN can serve as the target of miR-340-5p. In addition, TUG1 served as a miR-340-5p ceRNA, which promotes PTEN modulation. Furthermore, TUG1 overexpression decreased miR-340-5p's capacity to fend against CIRI. Conclusively, this work proved that in CIRI, targeting the TUG1/miR-340-5p/PTEN regulatory axis is a viable approach for the treatment of ischemic stroke.

RESUMEN

Exposure to arsenic, an environmental contaminant, is known to cause arsenicosis and cancer. Although considerable research has been conducted to understand the underlying mechanism responsible for arsenic-induced cancers, the precise molecular mechanisms remain unknown, especially at the epigenetic regulation level. Long non-coding RNAs (LncRNAs) that have been shown to mediate various biological processes, including proliferation, apoptosis, necrosis, and mutagenesis. There are few studies on LncRNAs and biological damage caused by environmental pollutants. The LncRNAs taurine upregulated gene 1 (TUG1) regulates cell growth both in vitro and in vivo, and contributes its oncogenic role. However, the precise roles and related mechanisms of arsenic-induced cell apoptosis are still not fully understood owing to controversial findings in the literature. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed higher expression levels of TUG1 in people occupationally exposed to arsenic than in individuals living away from the source of arsenic exosure (N = 25). In addition, the results suggested that TUG1 was involved in arsenic-induced apoptosis. Furthermore, knockdown experiments showed that silencing of TUG1 markedly inhibited proliferation, whereas depletion of TUG1 led to increased apoptosis. The TUG1-small interfering RNA (siRNA) combination with arsenic (3 µM/L) slightly increased apoptosis compared with the TUG1-siRNA. Additionally, the knockdown experiments showed that the silencing of TUG1 by siRNA inhibited proliferation and promoted apoptosis by inducing p53, p-p53 (ser392), FAS, BCL2, MDM2, cleaved-caspase7 proteins in 16HBE cells. These results indicated that arsenic mediates the upregulation of TUG1 and induces cell apoptosis via activating the p53 signaling pathway.

Asunto(s)

RESUMEN

Long non-coding RNA taurine-upregulated gene 1 (TUG1) plays pivotal roles in angiogenesis, an important mechanism of neural repair after intracerebral hemorrhage (ICH). However, the role of TUG1 in angiogenesis following ICH is not clear. Therefore, in this study, we investigated the role and the underlying mechanism of TUG1 in neurologic impairment and cerebral angiogenesis following ICH. The ICH rat model was established and then rats were injected with TUG1-expressing plasmid (pcDNA-TUG1) or miR-26a mimic, a critical regulator of VEGF-mediated angiogenesis. We confirmed the overexpression of TUG1 and miR-26a by qRT-PCR. The neurological deficits of ICH rats were evaluated by modified neurological severity scores. The expression of angiogenesis markers VEGF and CD31 were examined by immunohistochemistry and western blot. The interaction between TUG1 and miR-26a was determined by luciferase reporter assay. Our results showed that ICH caused a marked upregulation of TUG1 and a significant downregulation of miR-26a. TUG1 overexpression led to the deterioration of neurologic function and inhibited cerebral angiogenesis in ICH rats. In contrast, overexpression of miR-26a alleviated the neurologic damage and promoted cerebral angiogenesis in ICH rats, but these could be attenuated by TUG1 overexpression. Furthermore, TUG1 directly bound to miR-26a and inhibited its expression. Importantly, TUG1 overexpression inhibited the expression of VEGF by targeting miR-26a. In conclusion, our results indicated that TUG1 aggravated ICH-mediated injury by suppressing angiogenesis by downregulating miR-26a. This suggests a rationale for targeting TUG1/miR-26a in the therapy of ICH.

RESUMEN

Context: Recent studies confirmed that dysregulation of long noncoding RNAs (lncRNAs) is a potential contributor to the development and progression of colon cancer. However, the prognostic value of these RNA molecules remains controversial. Aims: This study aimed to investigate the expression of taurine-upregulated gene-1 (TUG1) lncRNA in colon cancer and its clinical implications. Subjects and Methods: A retrospective study on 47 formalin-fixed, paraffin-embedded samples of surgically resected primary colon cancer specimens was done. Total RNA purified from the colon cancer samples and noncancer adjacent tissue sections was quantified by real-time reverse transcription-polymerase chain reaction (qRT-PCR) to assess TUG1 relative expression levels normalized to GAPDH endogenous control. Also, in silico data analysis was applied. Statistical Analysis Used: The relative expression levels were calculated using the LIVAK method. The survival rates were assessed using the Kaplan-Meier curves and the Cox proportional model. P < 0.05 was considered statistically significant. Results: TUG1expression in the colon cancer specimens was significantly overexpressed (median = 21.50, interquartile range [IQR]: 7.0-209.2; P = 0.001) relative to the noncancerous tissues. In silico analysis confirmed TUG1 upregulation in colon carcinoma (median = 13.92, IQR: 13.5-1432). There were no significant associations between TUG1 expression and clinicopathological characteristics, such as the site, grade, stage, histopathological type, or the rates of lymphovascular invasion and relapse. Similarly, Kaplan-Meir and Cox multivariate regression analyses showed that TUG1 expression could not predict the overall survival and progression-free survival in colon cancer patients of our population. Conclusions: This study confirms the overexpression of TUG1 lncRNA in colon cancer tissues. Larger sample size is warranted to further elucidate the specific role of TUG1 in colon cancer.

Asunto(s)

RESUMEN

Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.

RESUMEN

OBJECTIVE: Accumulating evidence has demonstrated that lncRNA Taurine-upregulated gene 1 (TUG1) plays an important role in regulation of cell morphology, migration, proliferation and apoptosis. Our aim was to evaluate the oncogenic role of TUG1 in type I Endometrial Carcinoma (EC) and explore the precise mechanism of TUG1 involved in tumor progression. MATERIALS AND METHODS: The GSE17025 data set was used to analyze the correlation of TUG1 expression with type I EC patients' prognosis. Furthermore, TUG1 expression profiles were measured by qRT-PCR from carcinoma tissues and adjacent nonneoplastic tissues (NNT) of 105 type I EC patients. The regulation of epithelial-mesenchymal transition (EMT) related molecules, p-AKT and AKT by TUG1 knockdown was investigated using Western blot analysis; meanwhile, the oncogenic roles of TUG1 were evaluated using cell viability and transwell migration/invasion assay in Hec-1-A and Ishikawa cell lines. RESULTS: Firstly, we observed a significant association between higher TUG1 expression and lower survival rate in type I EC patients using the GSE17025 data set. A significant elevation of TUG1 levels was confirmed in type I EC tissues compared with NNT in the 105 type I EC patients, and high expression of TUG1 was associated with lymph vascular space invasion (LVSI) and lymph node metastasis (LNM). Subsequently, TUG1 knockdown could remarkably inhibit the Hec-1-A and Ishikawa cell invasion and migration in the functional experiment. Furthermore, our results showed that the protein levels of E-cadherin increased and N-cadherin decreased significantly, while ß-catenin and Vimentin were not significantly altered upon TUG1 silencing in both Hec-1-A and Ishikawa cells. Finally, we found the p-AKT and AKT protein levels, and the rate of p-AKT/t-AKT has a tendency to be down-regulate in Hec-1-A cells, while the AKT pathway was not change significantly in Ishikawa cells after TUG1 knockdown. CONCLUSION: Collectively, our data reveal that TUG1 might be regarded as an oncogenic molecule that promotes type I EC cells metastasis leading to tumor progression, at least partially, by regulating E-N cadherin switch and the AKT pathway.

Asunto(s)

RESUMEN

OBJECTIVE: Long non-coding RNA (lncRNA) essentially controls many physiological and pathological processes of deep vein thrombosis (DVT). Based on that, lncRNA taurine upregulated gene 1 (TUG1)-involved angiogenesis of endothelial progenitor cells (EPCs) and dissolution of DVT was explored. METHODS: In the in-vitro experiments, EPCs were engineered with mimic, inhibitor, siRNA, and plasmid, after which tube formation, proliferation, migration, and apoptosis were checked. In the in-vivo experiments, a DVT mouse model was established. Before the DVT operation, the mice were injected with agomir, antagomir, siRNA, and plasmid. Subsequently, thrombosis and damage to the femoral vein were pathologically evaluated. TUG1, miR-92a-3p, and 3-Hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) expression in the femoral vein was tested. The relationship between TUG1, miR-92a-3p, and Hmgcr was validated. RESULTS: DVT mice showed suppressed TUG1 and Hmgcr expression, and elevated miR-92a-3p expression. In EPCs, TUG1 overexpression or miR-92a-3p inhibition promoted cellular angiogenesis, whereas Hmgcr silencing blocked cellular angiogenesis. In DVT mice, elevated TUG1 or inhibited miR-92a-3p suppressed thrombosis and damage to the femoral vein whilst Hmgcr knockdown acted oppositely. In both cellular and animal models, TUG1 overexpression-induced effects could be mitigated by miR-92a-3p up-regulation. Mechanically, TUG1 interacted with miR-92a-3p to regulate Hmgcr expression. CONCLUSION: Evidently, TUG1 promotes the angiogenesis of EPCs and dissolution of DVT via the interplay with miR-92a-3p and Hmgcr.

RESUMEN

Renal fibrosis is most common among chronic kidney diseases. Molecular studies have shown that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participate in renal fibrosis, while the roles of lncRNA taurine upregulated gene 1 (TUG1) and miR-140-3p in hyperuricemia-induced renal fibrosis remain less investigated. In this study, a rat hyperuricemia model is constructed by oral administration of adenine. TUG1, miR-140-3p, and cathepsin D (CtsD) expression levels in rat models are measured. After altering TUG1, miR-140-3p, or CtsD expression in modelled rats, biochemical indices, including uric acid (UA), serum creatine (SCr), blood urea nitrogen (BUN), and 24-h urine protein are detected, pathological changes in the renal tissues, and renal fibrosis are examined. In renal tissues from hyperuricemic rats, TUG1 and CtsD are upregulated, while miR-140-3p is downregulated. Inhibiting TUG1 or CtsD or upregulating miR-140-3p relieves renal fibrosis in hyperuricemic rats. Downregulated miR-140-3p reverses the therapeutic effect of TUG1 reduction, while overexpression of CtsD abolishes the role of miR-140-3p upregulation in renal fibrosis. Collectively, this study highlights that TUG1 inhibition upregulates miR-140-3p to ameliorate renal fibrosis in hyperuricemic rats by inhibiting CtsD.

Asunto(s)

RESUMEN

Melanoma is the most prevalent malignancy of cutaneous carcinomas. Taurine-upregulated gene 1 (TUG1), a lncRNA, is a pivotal regulator of cutaneous malignancies. The present study aimed to investigate the impact and possible mechanisms of action of TUG1 behind the progression of melanomas. Reverse transcription-quantitative PCR was conducted to detect the expression levels of TUG1, microRNA (miR)-145-5p and SOX2 in melanoma tissues and cell lines. Cell Counting Kit-8 (CCK-8) assays were performed to measure the proliferative ability of melanoma cells and transwell assays were used to examine the migration and invasion of melanoma cells. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were utilized to identify the interactions among TUG1, miR-145-5p and SOX2. Western blotting and immunohistochemical assays were performed to determine the expression profile of SOX2. The impact of TUG1 on melanoma tumorigenesis was assessed using tumorigenicity assays. TUG1 expression levels were elevated in melanoma tumor tissues and cell lines. Reduced TUG1 expression levels significantly inhibited the proliferative, migratory and invasive abilities of melanoma cells. The expression levels of miR-145-5p were decreased in melanoma tumor tissues and cell lines. TUG1 directly targeted miR-145-5p and downregulated miR-145-5p. Upregulation of TUG1 counteracted the promotion of the proliferative, migratory and invasive abilities of melanoma cells induced by the overexpression of miR-145-5p. SOX2 was a target of miR-145-5p and its expression was negatively regulated by miR-145-5p, while positively regulated by TUG1. TUG1 regulated SOX2 expression through sponging miR-145-5p. Silencing of TUG1 also inhibited melanoma tumorigenesis in mice. In conclusion, the TUG1/miR-145-5p/SOX2 axis regulated the migration and invasion of melanoma cells.

RESUMEN

BACKGROUND: Increasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized. METHODS: The expression levels of TUG1, miR-524-5p, and sine oculis homeobox homolog 1 (SIX1) were determined using quantitative real-time PCR. The regulatory relationships were confirmed by dual-luciferase reporter assay. Cell proliferation and invasion were assessed using Cell Counting Kit 8 and transwell assays. Glucose uptake, cellular levels of lactate, lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) were detected using commercially available kits. Silencing of TUG1 or SIX1 was performed by lentivirus transduction. Protein levels were measured by immunoblotting. RESULTS: Cancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, and glycolysis in HepG2 cells by releasing TUG1. The promotive effects of CAFs-secreted exosomes were attenuated by silencing of TUG1. TUG1 and SIX1 are targets of miR-524-5p. SIX1 knockdown inhibited the promotive effects of miR-524-5p inhibitor. Silencing of TUG1 suppressed tumor growth and lung metastasis and therefore increased survival of xenograft model mice. We also found that TUG1 and SIX1 were increased in HCC patients with metastasis while miR-524-5p was decreased in HCC patients with metastasis. CONCLUSIONS: CAFs-derived exosomal TUG1 promoted migration, invasion, and glycolysis in HCC cells via the miR-524-5p/SIX1 axis. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for HCC in future.

Asunto(s)

RESUMEN

he incidence of obesity and type 2 diabetes mellitus (T2DM) is increasing year by year and shows a trend towards younger age groups worldwide. It has become a disease that endangers the health of individuals all over the world. Among numerous weight loss surgeries, sleeve gastrectomy (SG) has become one of the most common surgical strategies for the treatment of T2DM. However, SG­mediated alterations to the molecular mechanism of metabolism require further investigation. Thus, reverse transcription­quantitative PCR was used to detect the expression levels of long non­coding (lnc)RNA taurine­upregulated gene 1 (TUG1), Sirtuin 1 (SIRT1), AMP­activated protein kinase (AMPK) and uncoupling protein 2 (UCP2) in the serum of T2DM patients, as well as in HIEC­6 and SW480 cells following treatment with high glucose and high fat (HGHF). Protein expression was detected by western blotting. Cell Counting Kit­8 assays were performed to analyze cell viability, and flow cytometry and a TUNEL assay was performed to evaluate cell apoptosis. The secretion of ILs in the culture medium was detected by conducting ELISAs. The results showed that lncRNA TUG1 and UCP2 expression was upregulated, SIRT1 and AMPK expression levels were decreased by SG. Under HGHF conditions, HIEC­6 and SW480 cell viability was inhibited, apoptosis was promoted, TUG1 expression was downregulated, and SIRT1 and AMPK expression levels were upregulated. The secretory levels of IL­1ß, IL­6 and IL­8 were increased, whereas the secretion of IL­10 was decreased under HGHF conditions. lncRNA TUG1 overexpression significantly reversed the effects of HGHF on cell viability, apoptosis and SIRT1, AMPK, UCP2 and Bcl­2 expression levels. Together, the findings of the present study demonstrated that lncRNA TUG1 alleviated the damage induced by HGHF in intestinal epithelial cells by downregulating SIRT1 and AMPK expression, and upregulating UCP2 expression. Thus, the lncRNA TUG1/AMPK/SIRT1/UCP2 axis may serve an important role in the treatment of T2DM.

Asunto(s)

RESUMEN

Taurine-upregulated gene 1 (TUG1) is a long noncoding RNA (lncRNA) that has previously been linked to the development and progression of several cancer types. Its expression and mechanistic role in retinoblastoma (RB), however, remains to be established. Herein, we found that RB tissue samples exhibited TUG1 upregulation. RB cell lines similarly exhibited marked TUG1 upregulation. Real-time cellular analysis (RTCA) and colony formation assays were then used to gauge RB cell proliferation, while transwell assays were conducted to assess the metastatic and invasive potential of these cells. In these assays, TUG1 upregulation was found to promote RB cell proliferative, migratory, and invasive activity while inducing the epithelial-mesenchymal transition (EMT). Subsequent quantitative real-time polymerase chain reaction (qPCR) and Western blotting indicated that this lncRNA functions at least in part by influencing the expression of Notch signaling pathway genes, which were downregulated following TUG1 knockdown in RB cells. Together, these data suggested that TUG1 can promote RB cell malignancy via the Notch signaling and EMT pathways, contributing to negative patient outcomes.

Asunto(s)

RESUMEN

The maxillofacial region in the human body is susceptible to fracture and corresponding soft tissue injury. In the current study, the effect of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) on maxillofacial fracture development was investigated. In total, 50 patients diagnosed with maxillary fracture and 50 healthy volunteers were enrolled in this study. Participants' TUG1 expression level in serum was measured using reverse transcription-quantitative (RT-q)PCR. After transfection with small interfering (si)-TUG1, microRNA (miR)-214 mimic, miR-214 inhibitor, bone morphogenetic protein 2 (BMP2) mimic or a combination, the biological behavior of osteoblasts was evaluated using MTT, Transwell assays, RT-qPCR, flow cytometry and western blot analysis. Recovery experiments were used to explore the potential mechanism. Results demonstrated that TUG1 expression was decreased in the serum of patients with maxillary fractures. Knockdown of TUG1 repressed viability, migration and differentiation and induced apoptosis of osteoblasts. StarBase v2.0 revealed that TUG1 served as a sponge for miR-214 and BMP2 is a direct target of miR-214. Altogether, it was revealed that TUG1 expression was decreased in patients with maxillary fractures and TUG1 knockdown repressed the biological process of osteoblasts by sponging miR-214.

RESUMEN

The aim of the present study was to investigate the function of long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) in chronic obstructive pulmonary disease and further assess the underlying molecular mechanisms. Flow cytometry analysis was performed to detect cell apoptosis of human pulmonary microvascular endothelial cells (HPMECs) treated with 1% cigarette smoke extract (CSE). The activity of caspase-3 was measured using a Caspase-3 Activity assay kit and the protein expression of cleaved caspase-3, caspase-3 and Bcl-2 like 11 (BCL2L11) were measured using western blotting. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure the expression of TUG1 mRNA levels in the treated cells. The association between TUG1, the miR-9a-5p/BCL2L11 axis and with miR-9a-5p were predicted and verified using a dual luciferase reporter assay system. The mRNA expression of miR-9a-5p and BCL2L11, and the transfection efficiency were measured by RT-qPCR. The results showed that CSE induced cell apoptosis and increased lncRNA TUG1 expression in HPMECs. CSE significantly reduced the expression of miR-9a-5p in HPMECs compared with the control group. TUG1-short hairpin RNA relieved cell apoptosis induced by CSE by upregulating miR-9a-5p in HPMECs. The present study predicted and verified that BCL2L11 is a direct target of miR-9a-5p. The mRNA expression of BCL2L11 was increased in HPMECs following CSE treatment compared with the control group. miR-9a-5p mimic and BCL2L11-plasmid markedly increased the expression of miR-9a-5p and BCL2L11, respectively. miR-9a-5p mimic reversed the increase in cell apoptosis induced by CSE by inhibiting BCL2L11 expression in HPMECs. To conclude, the present study demonstrated that lncRNA TUG1 exerted roles in cell apoptosis induced by CSE through modulating the miR-9a-5p/BCL2L11 axis.

RESUMEN

Temozolomide (TMZ) is currently one of the first­line drugs used for the treatment of high­grade gliomas. However, TMZ resistance results in unsatisfactory therapeutic effects in gliomas. Cancer stem cells (CSCs) have recently been determined to serve a pivotal regulatory role in tumor metastasis, recurrence and chemoresistance. In addition, numerous reports have shown that long non­coding RNAs (lncRNAs) exert an essential role in the occurrence and development of tumors, and can be used as biomarkers for tumor diagnosis and treatment. Among them, studies have revealed that taurine upregulated gene 1 (TUG1) exhibits an important regulatory effect on the malignant biological behavior of glioma cells. Moreover, it has been reported that enhancer of Zeste homolog 2 polycomb repressive complex subunit 2 (EZH2) promotes tumorigenesis, including in glioma. However, the underlying mechanism of the interaction of TUG1 and EZH2 with CSCs of glioma remains elusive, and thus requires further clarification. The present study aimed to explore the role of TUG1 and EZH2 in TMZ resistance in glioma. Cell Counting Kit­8, colony formation,sphere formation and Annexin V­FITC/PI assays were used to detect the proliferation, clone formation efficiency, stemness and apoptosis of TMZ­resistant glioma cells. Xenograft tumor assay was used to detect the effect of TUG1 on the tumorigenesis of TMZ­resistant glioma cells. The present findings demonstrated that TUG1 exhibited a low expression in glioma cells, while EZH2 expression was the opposite. Moreover, it was observed that A172/TMZ cells possessed higher CSCs­like properties compared with parent cells, and that TUG1 and EZH2 were abnormally expressed in A172/TMZ cells. Knockdown of TUG1 or overexpression of EZH2 promoted A172/TMZ cell proliferation and CSCs­like properties, as well as inhibited their apoptosis, thereby enhancing the TMZ resistance of A172/TMZ cells. Furthermore, it was found that TUG1 alleviated the TMZ resistance of A172/TMZ cells by inhibiting EZH2 expression. Of note, overexpression of TUG1 inhibited the tumorigenicity of A172/TMZ cells by downregulating EZH2 expression in vivo. Collectively, the present study demonstrated that TUG1 served an essential regulatory role in TMZ resistance of gliomas.

Asunto(s)

RESUMEN

Long non-coding RNAs (lncRNAs) are a group of non-protein coding RNAs with a length of more than 200 bp. The lncRNA taurine up-regulated gene 1 (TUG1) is abnormally expressed in many human malignant cancers, where it acts as a competitive endogenous RNA (ceRNA), regulating gene expression by specifically sponging its corresponding microRNAs. In the present review, we summarised the current understanding of the role of lncRNA TUG1 in cancer cell proliferation, metastasis, angiogenesis, chemotherapeutic drug resistance, radiosensitivity, cell regulation, and cell glycolysis, as well as highlighting its potential application as a clinical biomarker or therapeutic target for malignant cancer. This review provides the basis for new research directions for lncRNA TUG1 in cancer prevention, diagnosis, and treatment.

Asunto(s)

RESUMEN

Patients with heart failure with preserved ejection fraction (HFPEF) account for ~50% of all cases of heart failure and their clinical prognosis is poor. The present study attempted to investigate the diagnostic value of circulating long non-coding RNA taurine upregulated gene 1 (TUG1) for HFPEF in subjects with hypertension. Between January 2017 and January 2019, 80 aged/elderly hypertensive patients with or without HFPEF were recruited for the present study. The concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the serum was measured using ELISA and TUG1 expression levels were determined using reverse transcription-quantitative PCR. Echocardiography was used for the determination of cardiac function. The results indicated that the levels of NT-proBNP and TUG1 were increased in the serum of hypertensive patients with HFPEF. Pearson analysis demonstrated that NT-proBNP and TUG1 were positively correlated with the left atrial diameter and negatively correlated with the ratio of the peak flow velocity in the early diastolic phase to the peak flow velocity in the late diastolic phase. In addition, a positive correlation was confirmed between TUG1 and NT-proBNP levels. Receiver operating characteristic curve analysis demonstrated that TUG1 and NT-proBNP were useful biomarkers for the diagnosis of HFPEF. In conclusion, it was observed that NT-proBNP and TUG1 were increased in the serum of hypertensive patients with HFPEF. Furthermore, TUG1 and NT-proBNP were indicated to be useful plasma biomarkers for the diagnosis of HFPEF.

RESUMEN

Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.

RESUMEN

Objective: To study the association of the expression levels of long noncoding RNA Taurine-upregulated gene 1 (lncRNA TUG1) and TUG1 polymorphisms with knee osteoarthritis (KOA). Materials and Methods: A total of 255 KOA patients and 255 controls from May 2017 to December 2019 were selected for the study. Sanger sequencing was conducted to detect the genotypes of the TUG1 rs5749201, rs7284767, and rs886471 loci in all study subjects. Unconditional logistic regression analysis was used to calculate odds ratios and 95% confidence intervals, and the associations between the TUG1 rs574901, rs7284767 and rs886471 loci and KOA risk were analyzed. Multifactor dimensionality reduction was used to analyze the interactions among alleles at the three TUG1 loci examined. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of TUG1 lncRNA in plasma. Results: A total of 255 KOA patients and 255 control subjects completed the study. After adjusting for the factors of gender, age, body mass index, smoking history, drinking history, and family history, we found that the carriers of the A allele of the TUG1 rs5749201 locus were 1.36 times more likely to develop KOA than the carriers of the T allele (95% confidence interval [CI] = 1.05-1.75, p = 0.02); the G allele of the rs7284767 locus was a protective factor for KOA (odds ratio [OR] = 0.71, 95% CI = 0.54-0.92, p = 0.01); and the allelic variation at rs886471 G > T led to an increased risk of KOA by 2.34 times (95% CI = 1.53-3.57, p < 0.01). We also found that the GAG haplotype for the three loci was significantly associated with the increased risk of KOA (OR = 2.77, 95% CI = 1.67-4.57, p < 0.01). There was no correlation found between the TUG1 rs886471, rs5749201, and rs7284767 single nucleotide polymorphisms loci and the severity of KOA. The allelic variation at TUG1 rs5749201 T > A, rs886471 T > G were associated with decreased levels of TUG1 lncRNA in the plasma of the subjects, while the allelic variation at rs7284767 A > G was associated with increased levels of TUG1 lncRNA in plasma (p = 0.01, p < 0.01, p < 0.01). Conclusion: Plasma TUG1 lncRNA levels and loci at the TUG1 rs5749201, rs7284767, and rs886471 loci are associated with KOA risk.

Asunto(s)

RESUMEN

BACKGROUND: Retinoblastoma (RB), depicted as an aggressive eye cancer, mainly occurs in infancy and childhood and is followed by high mortality and poor prognosis. Increasing evidence has revealed that long noncoding RNA taurine upregulated gene 1 (TUG1) is closely linked to the progression of diverse cancers. Nonetheless, the specific function and molecular regulatory mechanism of TUG1 in RB still need to be explored. METHODS: To explore the specific role of TUG1 in RB. TUG1 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), caspase-3, terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and western blot assays were utilized to study the role of TUG1 in RB. The binding relation between miR-516b-5p and TUG1 or hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase (H6PD) was analyzed by luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: The expression of TUG1 was upregulated in RB cells. TUG1 knockdown repressed proliferation ability and promoted apoptosis ability of RB cells. Moreover, TUG1 could bind with miR-516b-5p, which targeted H6PD in RB. In addition, the expression of H6PD was negatively and positively regulated by miR-516b-5p and TUG1 in RB, respectively. Finally, H6PD overexpression could partially offset the effects of TUG1 deficiency on cell proliferation and apoptosis. CONCLUSIONS: TUG1 promoted the development of RB by sponging miR-516b-5p to upregulate H6PD expression, which might provide a new thought for researching RB-related molecular mechanism.