lncRNA TUG1 Research Articles

LncRNA TUG1 regulates mir-34a-5p / SIRT6 to participate in benzene-induced hematotoxicity through PI3K / AKT /mTOR signaling pathway

LncRNA TUG1 plays pivotal roles in various diseases. However, its exact roles in benzene - induced hematotoxicity remain unclear. Herein, we aimed to investigate the role and mechanism of TUG1 in hematoxic injuries caused by benzene. In the current study, TUG1 was found dramatically decreased in WBCs of benzene exposure workers and negatively correlated with benzene exposure duration and urine SPMA. In vitro assays demonstrated that TUG1 overexpression attenuated 1,4-BQ-caused suppression of cell viability and proliferation, and promotion of ROS generation and apoptosis via PI3K/AKT/mTOR pathway. Bioinformatic prediction and molecular assay validated miR-34a-5p was negatively regulated by TUG1. The miR-34a-5p was upregulated in 1,4-BQ treated cells and downregulated in TUG1 overexpression cells. Moreover, miR-34a-5p upregulation partially reversed the protective effects of TUG1 overexpression on 1,4-BQ - caused cytotoxicity. Furthermore, SIRT6 was a downstream target gene of miR-34a-5p, whose expression was reduced in miR-34a-5p upregulation cells and elevated in TUG1 overexpression cells. Upregulated SIRT6 could counteract accelerated cytotoxicity mediated by miR-34a-5p upregulation after 1,4-BQ treatment. Taken together, our study revealed that the critical role of the TUG1/miR-34a-5p/SIRT6 axis in benzene-caused hematotoxicity, and provided scientific basis for further understanding the epigenetic regulatory mechanisms underlying benzene hematotoxicity.

M6A RNA Methylation-Mediated TUG1 Stability Maintains Mitochondrial Homeostasis during Kidney Aging by Epigenetically Regulating PGC1-α Expression.

Aging is a significant risk factor for the increased incidence of acute kidney injury and chronic kidney disease, posing significant challenges to global public health. The role of N6-methyladenosine (m6A) in the development of chronic kidney disease has been reported, but the regulatory mechanism of m6A in kidney aging remains unclear. In this study, we identified a long non-coding RNA (lncRNA), called TUG1, which exhibited a significantly decreased level of m6A modification in human aged kidney through the m6A-lncRNA epitranscriptome microarray. Bioinformatics analysis and machine learning predicted that TUG1 formed potentially strong interaction with PGC1-α. RIP and ChIP analysis supported that TUG1 promoted proliferator-activated receptor γ coactivator-1α (PGC1-α) expression by directly interact with its TBE region, thereby impacting mitochondrial quality control, cellular senescence and renal fibrosis. Silencing the RNA m6A methylase METTL14 or the reader protein IGF2BP2 resulted in the weakened stability of LncRNA TUG1, contributing to an imbalance in mitochondrial quality control. Our study demonstrated that Our study demonstrated that the m6A modification and stability of TUG1 was mediated by METTL14 in an IGF2BP2-dependent manner, and modulate the mitochondrial homeostasis in kidney aging by direct targeting PGC-1α. These findings provide a new perspective on potential therapeutic targets for kidney aging.

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.

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

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). 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. 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. Our new findings suggest that the EZH2 gene, plasma lncRNA TUG1, and FEZF1-AS1 may contribute, as valuable biomarkers, to AD diagnosis.

TUG1 exacerbates cerebral ischemia-reperfusion injury through miR-340-5p-mediated PTEN.

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-2H-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.

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.

Level of long noncoding RNA taurine upregulated gene 1 after narrow band-ultraviolet B phototherapy in vitiligo

Background Vitiligo is a skin disease that is characterized by depigmenting lesions as a result of melanocytes destruction. Long noncoding Taurine upregulated gene 1 (lnc TUG-1) is one of the long noncoding RNA (lnc RNA) family members. The role of lncRNA TUG1 in melanogenesis has been investigated in recent studies. Objective To investigate the impact of narrow-band ultraviolet B (NB-UVB) on lncTUG-1 expression in vitiligo. Patients and methods The first step of this work was a case control study that included thirty vitiligo patients and thirty healthy controls. four mm skin biopsies were taken from normal skin in healthy controls and from depigmenting lesions in vitiligo patients. The second step was a prospective single-arm interventional study in which patients were subjected to 12 weeks of NB-UVB phototherapy and biopsies were taken from repigmenting areas. Biopsies were kept frozen at −80°C till by real-time polymerase chain reaction was conducted to evaluate the lnc TUG-1 expression. Results The mean lnc TUG-1 expression in skin tissue biopsies of the vitiligo patients was significantly lower compared with control skin biopsies (0.307±0.202 ng/mg vs 1.03±0.063 pg/mg, respectively, P<0.001). Although the level of lnc TUG-1 was not normalized, the mean value of lnc TUG-1 significantly increased after 12 weeks treatment with NB-UVB compared with its value before phototherapy (0.0687 ng/mg vs. 0.307 ng/mg, respectively, P<0.001). Conclusion The lnc TUG-1 could be a possible player in the pathogenesis of vitiligo and repigmentation of vitiligo after NB-UVB phototherapy.

Retracted] LncRNA TUG1 serves an important role in hypoxia‑induced myocardial cell injury by regulating the miR‑145‑5p‑Binp3 axis.

Following the publication of this article, a concerned reader drew to the Editor's attention that, for several of the figures showing the results of Transwell migration and invasion assay experiments, unexpected areas of similarity were identified in terms of cellular patterns comparing among data panels where the results from differently performed experiments were intended to have been shown, although the areas immediately surrounding these areas often featured comparatively different distributions of cells. Moreover, several of the figures contained invasion/migration assay data that were strikingly similar to data that had appeared in articles published previously by different authors at different research institutes. In addition, the western blots in this article were presented with atypical, unusually shaped and possibly anomalous protein bands in many cases. After having conducted an internal investigation, the Editor of Molecular Medicine Reports has reached the conclusion that the potentially anomalous data in this paper were unlikely to have arisen by coincidence. Therefore, on the grounds of a lack of confidence in the integrity of these data, and given the fact that some of the data were strikingly similar to that which had been published previously in other articles and journals, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused, and thanks the concerned reader for drawing this matter to our attention. [Molecular Medicine Reports 42: 2422‑2430, 2018; DOI: 10.3892/mmr.2017.8116].

Expression of concern: LncRNA TUG1 facilitates proliferation, invasion and stemness of ovarian cancer cell via miR-186-5p/ZEB1 axis.

Expression of concern: LncRNA TUG1 facilitates proliferation, invasion and stemness of ovarian cancer cell via miR-186-5p/ZEB1 axis.

Exploring the Evolving Significance of lncRNA TUG1-mediated Signaling Pathways in Breast Cancer

Abstract: Breast cancer is one of the most common malignancies in women worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most common kinds of invasive breast cancer. Several genetic, epigenetic, and environmental factors could trigger the pathogenesis of breast cancer. Breast cancer treatment generally includes surgery, radiation therapy, chemotherapy, hormonal treatment, targeted therapy, immunotherapeutic, neoadjuvant systemic therapy, and systemic therapy. Although several classical treatment methods are used in cancer therapy, molecular-based strategies can open a new perspective for breast cancer treatment. Previous studies reported that long non-coding RNAs (lncRNAs) play important roles in cancer development and progression. LncRNA TUG1 was found to target several miRNAs and regulate breast cancer cell behavior. TUG1 can induce cell proliferation and invasion of breast cancer cells via downregulation of some miRNAs. Therefore, TUG1 might be a potent biomarker for the treatment of human cancer. In this review, we summarized the functional roles of TUG1 in breast cancer.

Retracted: Downregulation of miR-221-3p by LncRNA TUG1 Promoting the Healing of Closed Tibial Fractures in Mice.

[This retracts the article DOI: 10.1155/2022/1624446.].

LncRNA TUG1 as potential novel biomarkerfor prognosis of cardiovascular diseases.

Globally, cardiovascular diseases (CVDs) are among the leading causes of death. In light of the high prevalence and mortality of CVDs, it is imperative to understand the molecules involved in CVD pathogenesis and the signaling pathways that they initiate. This may facilitate the development of more precise and expedient diagnostic techniques, the identification of more effective prognostic moleculesand the identification of potential therapeutic targets. Numerous studies have examined the role of lncRNAs, such as TUG1, in CVD pathogenesis in recent years. According to this review article, TUG1 can be considered a biomarker for predicting the prognosis of CVD.

Interplay of LncRNA TUG1 and TGF-β/P53 Expression in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore the therapeutic targets of CRC. Long non-coding RNA taurine upregulated gene 1 (LncRNA TUG1) was initially discovered as a transcript upregulated by taurine and is observed to be expressed in numerous human cancers. The Study Aim: This article was to explore the correlation between transforming growth factor-beta (TGF-β)/tumor protein 53 (P53) signaling mechanisms as regulators for LncRNA TUG1 in Egyptian patients with CRC. Immunohistochemical (IHC) staining was achieved to study TGF-β and P53 expression in CRC specimens vs. normal colonic specimens and quantitative real-time PCR (qRT-PCR) was used to analyze LncRNA TUG1, TGF-β, and P53 relative gene expression in 96 tissue specimens (neoplastic specimens and the corresponding adjacent non-neoplastic specimens). The expressions of LncRNA TUG1, TGF-β, and P53 were overexpressed significantly in CRC specimens as opposed to the matched neighboring non-neoplastic specimens (P<0.001), also LncRNA TUG1 was significantly positively correlated to the expression of TGF-β and P53 (r=0.89, 0.91 respectively, P<0.001). These findings reveal that LncRNA TUG1 may be a molecular component in the TGF-β/P53 signaling pathway, and LncRNA TUG1 could function as a CRC possible oncogene. LncRNA TUG1 may serve as a potential oncogene for CRC. The TGF-β/P53/LncRNA TUG1 interactions may be employed as potential targets for CRC diagnosis, prognostic evaluation, and cure.

Regulation of mitochondrial calcium uniporter expression and calcium-dependent cell signalling by lncRNA Tug1 in cardiomyocytes.

Cardiomyocyte calcium homeostasis is a tightly regulated process. The mitochondrial calcium uniporter (MCU) complex can buffer elevated cytosolic Ca2+ levels and consists of pore-forming proteins including MCU, and various regulatory proteins such as mitochondrial calcium uptake proteins 1 and 2 (MICU1/2). The stoichiometry of these proteins influences the sensitivity to Ca2+ and activity of the complex. However, the factors that regulate their gene expression remain incompletely understood. Long non-coding RNAs (lncRNAs) regulate gene expression through various mechanisms, and we recently found that the lncRNA Tug1 increased the expression of Mcu and associated genes. To further explore this, we performed antisense LNA knockdown of Tug1 (Tug1 KD) in H9c2 rat cardiomyocytes. Tug1 KD increased MCU protein expression, yet pyruvate dehydrogenase dephosphorylation, which is indicative of mitochondrial Ca2+ uptake, was not enhanced. However, RNA-seq revealed that Tug1 KD increased Mcu along with differential expression of >1000 genes including many related to Ca2+ regulation pathways in the heart. To understand the effect of this on Ca2+ signalling, we measured phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and its downstream target cAMP Response Element-Binding protein (CREB), a transcription factor known to drive Mcu gene expression. In response a Ca2+ stimulus, the increase in CAMKII and CREB phosphorylation was attenuated by Tug1 KD. Inhibition of CaMKII, but not CREB, partially prevented the Tug1 KD-mediated increase in Mcu. Together, these data suggest that Tug1 modulates MCU expression via a mechanism involving CAMKII and regulates cardiomyocyte Ca2+ signalling which could have important implications for cardiac function.

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.

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.

Increased LncRNA TUG1 expression level impacted ankylosing spondylitis risk, association with disability, and patients’ quality of life

Increased LncRNA TUG1 expression level impacted ankylosing spondylitis risk, association with disability, and patients’ quality of life

The study of long noncoding RNA TUG 1 and ZEB2-AS1 expression in newly diagnosed Egyptian adult acute myeloid leukemia patients

BackgroundThe hematopoietic malignancy acute myeloid leukemia is a fatal disease with poor clinical prognoses. Long non-coding RNA taurine-upregulated gene1 (lncRNA TUG1) and zinc finger E-box binding homeobox 2 antisense RNA1 (lncRNA ZEB2-AS1) are reported to participate in the development and progression of different types of malignancies. The goal of the current study was to evaluate the prognostic value of the lncRNAs TUG1 and ZEB2-AS1 as well as their various expression patterns in newly diagnosed Egyptian adult acute myeloid leukemia patients.MethodsWe assessed the expression levels of both lncRNA TUG1 and lncRNA ZEB2-AS1 using the quantitative real-time reverse transcription polymerase chain reaction technique (qRT-PCR) in 80 newly diagnosed AML patients and 20 healthy subjects.ResultslncRNA TUG1 expression was significantly higher in the AML cases compared to the controls (P < 0.001), whereas lncRNA ZEB2-AS1 expression was considerably lower in the AML cases in comparison with the controls (P < 0.001). The expression levels of the lncRNAs ZEB2-AS1 and TUG1 exhibited a significantly positive association in the AML group (P < 0.001). There was no difference in overall survival (OS) and disease-free survival (DFS) between the groups with low and high lncRNA TUG1 expression (P = 0.139 and 0.918, respectively). Furthermore, the AML cases with higher lncRNA ZEB2-AS1 expression levels had shorter DFS than patients with lower lncRNA ZEB2-AS1 expression levels (P = 0.014), while OS did not significantly differ between the studied cases with lower and higher lncRNA ZEB2-AS1 expression (P = 0.589).ConclusionOverexpression of lncRNA TUG1 could serve as a diagnostic biomarker for Egyptian adult AML cases, while lncRNA ZEB2-AS1 high expression could be regarded as an indicator of poor outcome in Egyptian adult AML studied cases.

LncTUG1 contributes to the progression of hepatocellular carcinoma via the miR-144-3p/RRAGD axis and mTOR/S6K pathway

Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment. LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3′UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.