lncRNA Growth Arrest-specific Transcript 5 Research Articles

The Impact of lncRNA-GAS5/miRNA-200/ACE2 Molecular Pathway on the Severity of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2), which is responsible for coronavirus disease (COVID-19), potentially has severe adverse effects, leading to public health crises worldwide. In COVID-19, deficiency of ACE-2 is linked to increased inflammation and cytokine storms via increased angiotensin II levels and decreased ACE-2/Mas receptor axis activity. MiRNAs are small sequences of noncoding RNAs that regulate gene expression by binding to the targeted mRNAs. MiR-200 dysfunction has been linked to the development of ARDS following acute lung injury and has been proposed as a key regulator of ACE2 expression. LncRNA growth arrest-specific transcript 5 (GAS5) has been recently studied for its modulatory effect on the miRNA-200/ACE2 axis. The current study aims to investigate the role of lncRNA GAS5, miRNA-200, and ACE2 as new COVID-19 diagnostic markers capable of predicting the severity of SARS-CoV-2 complications. A total of 280 subjects were classified into three groups: COVID-19-negative controls (n = 80), and COVID-19 patients (n=200) who required hospitalization were classified into two groups: group (2) moderate cases (n = 112) and group (3) severe cases (n = 88). The results showed that the serum GAS5 expression was significantly down-expressed in COVID-19 patients; as a consequence, the expression of miR-200 was reported to be overexpressed and its targeted ACE2 was down-regulated. The ROC curve was drawn to examine the diagnostic abilities of GAS5, miR-200, and ACE2, yielding high diagnostic accuracy with high sensitivity and specificity. lncRNA-GAS5, miRNA-200, and ACE2 panels presented great diagnostic potential as they demonstrated the highest diagnostic accuracy for discriminating moderate COVID-19 and severe COVID-19 cases.

Electroacupuncture Promotes Nerve Regeneration and Functional Recovery Through Regulating lncRNA GAS5 Targeting miR-21 After Sciatic Nerve Injury

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.

Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling.

Macrophages are involved in the pathogenesis of allergic rhinitis (AR), but how these macrophages are polarized to M1 or M2 type is undetermined. Long non-coding RNA growth arrest specific transcript 5 (GAS5) is upregulated in exosomes isolated from nasal mucus of AR patients (AR-EXO) and aggravates nasal symptoms in AR mice. In the present study, we are aimed to elucidate the potential role of GAS5 in macrophage polarization during AR pathogenesis. An AR mice model was constructed. The potential function of GAS5 was evaluated by western blot, RNA immunoprecipitation (RIP), biotinylated RNA pull-down assay, co-immunoprecipitation (co-IP) assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry (IHC) staining. We found that GAS5 is upregulated in ovalbumin-treated human nasal epithelial cells RPMI 2650 (OVA-EXO) and nasal mucus of AR mice. OVA-EXO treatment or forced GAS5 expression promoted M1 macrophage polarization of peripheral blood monocytes (PB monocytes) and THP-1 macrophages in vitro. GAS5 overexpression aggravated the allergic nasal symptoms induced by OVA in AR mice and facilitated M1 macrophage polarization and allergic inflammation, while knockdown of GAS5 exhibited opposite effects in vivo. GAS5 activated NF-кB signaling via suppressing autophagy-dependent degradation of IKKα/β in macrophages. Furthermore, GAS5 acted as a scaffold to strengthen the interaction between mTORC1 and ULK1, thus impaired ULK1/ATG13-mediated autophagy via increasing mTORC1 activity. Finally, restored autophagy by ATG13 overexpression suppressed the effect of GAS5 on M1 macrophage polarization. In conclusion, these results suggested that exosomal transfer of GAS5 promoted M1 macrophage polarization via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling in allergic rhinitis.

Oversized liposomes boost macrophage-targeted RNA delivery to regulate macrophage polarity

Oversized liposomes boost macrophage-targeted RNA delivery to regulate macrophage polarity

LncRNA GAS5 regulated by FTO-mediated m6A demethylation promotes autophagic cell death in NSCLC by targeting UPF1/BRD4 axis.

Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been shown to be a regulator for many cancers, including non-small cell lung cancer (NSCLC). Therefore, its role and mechanism in the process of NSCLC deserve to be further revealed. The expression levels of GAS5, fat mass and obesity-associated protein (FTO) and bromodomain-containing protein 4 (BRD4) were detected by quantitative real-time PCR. Western blot analysis was used to examine the protein expression of FTO, BRD4, up-frameshift protein 1 (UPF1) and autophagy-related markers. Methylated RNA immunoprecipitation was used to assess the m6A level of GAS5 regulated by FTO. Cell proliferation and apoptosis were determined using MTT assay, EdU assay and flow cytometry. Autophagy ability was assessed by immunofluorescence staining and transmission electron microscope. Xenograft tumor model was constructed to explore the effects of FTO and GAS5 on NSCLC tumor growth in vivo. The interaction between UPF1 and GAS5 or BRD4 was confirmed by pull-down assay, RIP assay, dual-luciferase reporter assay, and chromatin immunoprecipitation. Fluorescent in situ hybridization was used to analyze the co-localization of GAS5 and UPF1. Actinomycin D treatment was employed to evaluate BRD4 mRNA stability. GAS5 was downregulated in NSCLC tissues and was associated with poor prognosis in NSCLC patients. FTO was highly expressed in NSCLC, and it inhibited GAS5 expression by reducing GAS5 m6A methylation level. GAS5 suppressed by FTO could promote the autophagic death of NSCLC cells in vitro and inhibit NSCLC tumor growth in vivo. In addition, GAS5 was able to interact with UPF1 to reduce the mRNA stability of BRD4. Knockdown of BRD4 reversed the inhibition of GAS5 or UPF1 silencing on the autophagic cell death of NSCLC. The findings of the study showed that lncRNA GAS5 mediated by FTO could contribute to the autophagic cell death of NSCLC by interacting with UPF1 to reduce BRD4 mRNA stability, suggesting that GAS5 might be a vital therapy target for NSCLC progression.

LncRNA GAS5 suppresses TGF-β1-induced transformation of pulmonary pericytes into myofibroblasts by recruiting KDM5B and promoting H3K4me2/3 demethylation of the PDGFRα/β promoter

BackgroundIdiopathic pulmonary fibrosis (IPF) is a condition that may cause persistent pulmonary damage. The transformation of pericytes into myofibroblasts has been recognized as a key player during IPF progression. This study aimed to investigate the functions of lncRNA growth arrest-specific transcript 5 (GAS5) in myofibroblast transformation during IPF progression.MethodsWe created a mouse model of pulmonary fibrosis (PF) via intratracheal administration of bleomycin. Pericytes were challenged with exogenous transforming growth factor-β1 (TGF-β1). To determine the expression of target molecules, we employed quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical and immunofluorescence staining. The pathological changes in the lungs were evaluated via H&E and Masson staining. Furthermore, the subcellular distribution of GAS5 was examined using FISH. Dual-luciferase reporter assay, ChIP, RNA pull-down, and RIP experiments were conducted to determine the molecular interaction.ResultsGAS5 expression decreased whereas PDGFRα/β expression increased in the lungs of IPF patients and mice with bleomycin-induced PF. The in vitro overexpression of GAS5 or silencing of PDGFRα/β inhibited the TGF-β1-induced differentiation of pericytes to myofibroblasts, as evidenced by the upregulation of pericyte markers NG2 and desmin as well as downregulation of myofibroblast markers α-SMA and collagen I. Further mechanistic analysis revealed that GAS5 recruited KDM5B to promote H3K4me2/3 demethylation, thereby suppressing PDGFRα/β expression. In addition, KDM5B overexpression inhibited pericyte–myofibroblast transformation and counteracted the promotional effect of GAS5 knockdown on pericyte–myofibroblast transformation. Lung fibrosis in mice was attenuated by GAS5 overexpression but promoted by GAS5 deficiency.ConclusionGAS5 represses pericyte–myofibroblast transformation by inhibiting PDGFRα/β expression via KDM5B-mediated H3K4me2/3 demethylation in IPF, identifying GAS5 as an intervention target for IPF.

LncRNA GAS5 as an Inflammatory Regulator Acting through Pathway in Human Lupus.

To investigate the contribution of GAS5 in the pathogenesis of SLE. Systemic Lupus Erythematosus (SLE) is characterized by aberrant activity of the immune system, leading to variable clinical symptoms. The etiology of SLE is multifactor, and growing evidence has shown that long noncoding RNAs (lncRNAs) are related to human SLE. Recently, lncRNA growth arrest-specific transcript 5 (GAS5) has been reported to be associated with SLE. However, the mechanism between GAS5 and SLE is still unknown. Find the specific mechanism of action of lncRNA GAS5 in SLE. Collecting samples of the SLE patients, Cell culture and treatment, Plasmid construction, and transfection, Quantitative real-time PCR analysis, Enzyme-linked immunosorbent assay (ELISA), Cell viability analysis, Cell apoptosis analysis, Western blot. In this research, we investigated the contribution of GAS5 in the pathogenesis of SLE. We confirmed that, compared to healthy people, the expression of GAS5 was significantly decreased in peripheral monocytes of SLE patients. Subsequently, we found that GAS5 can inhibit the proliferation and promote the apoptosis of monocytes by over-expressing or knocking down the expression of GAS5. Additionally, the expression of GAS5 was suppressed by LPS. Silencing GAS5 significantly increased the expression of a group of chemokines and cytokines, including IL-1β, IL-6, and THFα, which were induced by LPS. Furthermore, it was identified the involvement of GAS5 in the TLR4-mediated inflammatory process was through affecting the activation of the MAPK signaling pathway. In general, the decreased GAS5 expression may be a potential contributor to the elevated production of a great number of cytokines and chemokines in SLE patients. And our research suggests that GAS5 contributes a regulatory role in the pathogenesis of SLE, and may provide a potential target for therapeutic intervention.

LncRNA GAS5 suppresses inflammatory responses by inhibiting HMGB1 release via miR-155-5p/SIRT1 axis in sepsis

Sepsis comprises a lethal immunologic response due to infection. Increasingly, evidence has demonstrated the important role of long non-coding RNA growth arrest-specific transcript 5 (GAS5) in the regulation of sepsis. Nevertheless, the mechanisms by which GAS5 participates in the progression of sepsis remain unclear. Our study demonstrated the role and underlying mechanism of GAS5 in regulating lipopolysaccharide (LPS)-induced inflammation. In this study, GAS5 expression was found to be markedly decreased in serum samples of sepsis patients and a sepsis mouse model, and was negatively related with HMGB1 expression. GAS5 overexpression inhibited cell inflammatory responses by decreasing HMGB1 release. Furthermore, GAS5 inhibited LPS-mediated hyperacetylation and the release of HMGB1 by increasing the expression of sirtuin1 (SIRT1). Additionally, upregulated GAS5 attenuated inflammatory responses in vitro and vivo, and the knockdown of a miR-155-5p mimic and SIRT1 rescued the effects of GAS5 upregulation. Mechanistically, GAS5 sponged miR-155-5p to upregulate SIRT1, thereby inhibiting HMGB1 acetylation and release. In conclusion, our findings indicate that GAS5 suppresses inflammatory responses by modulating the miR-155-5p/SIRT1/HMGB1 axis in sepsis, providing a novel therapeutic target for inflammation in sepsis.

Highly Expressed lncRNA GAS5 in the Serum of Children with Mycoplasma pneumoniae Pneumonia and Its Effect on LAMPs-Induced Apoptosis and Inflammation.

The aim of the study was to explore the serum expression of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in Mycoplasma pneumoniae pneumonia (MPP) and its effect on lipid-associated membrane proteins (LAMPs)-induced apoptosis and inflammation. Totally, 56 children with MPP (MPP group) and 56 healthy children (NC group) were enrolled. lncRNA GAS5 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected using ELISA, and the high mobility family protein B1 (HMGBl) was detected by qRT-PCR. The methylated binding protein 2 (MECP2) was inhibited by gene silencing, and the expression of MECP2, TNF-α, IL-6, HMGBl, p-p65, and p-IκBα was measured. lncRNA GAS5 and TNF-α, IL-6, and HMGBl in the peripheral blood of the MPP group were positively correlated (P < 0.05). The expression of TNF-α, IL-6, HMGBl, and lncRNA GAS5 showed a positive correlation with that of LAMPs. The GAS5-siRNA group showed an increased cell survival rate compared with the scrambled-RNAi group (P < 0.05) while showing decreased apoptosis and cell death rates (P < 0.05). In addition, the expression of IL-6, TNF-α, HMGBl, p-p65, and p-IκBα was significantly reduced (P < 0.05). lncRNA GAS5 is highly expressed in the serum of children with MPP and inhibits LAMPs-induced apoptosis and alveolar macrophage inflammation.

LncRNA GAS5 promotes spermidine‑induced autophagy through the miRNA‑31‑5p/NAT8L axis in pulmonary artery endothelial cells of patients with CTEPH

Chronic thromboembolic pulmonary hypertension (CTEPH) is a leading cause of pulmonary hypertension. The present study investigated the mechanisms of long non-coding RNA growth arrest-specific transcript 5 (GAS5) on spermidine (SP)-induced autophagy. Pulmonary artery endothelial cells (PAECs) were collected from patients with CTEPH and the rat model. Immunofluorescence, Western blots, reverse transcription-quantitative polymerase chain reaction, bioinformatics, rapid amplification of cDNA ends assays, luciferase reporter assays, RNA-binding protein immunoprecipitation assays, GFP-LC3 adenoviruses, tfLC3 assays and transmission electron microscopy were performed. The results revealed that SP-induced autophagy increased GAS5 in PAECs. The upregulation of GAS5 enhanced and the downregulation of GAS5 reversed the roles of SP in PAECs. Furthermore, GAS5 promoted SP-induced autophagy in PAECs by targeting miRNA-31-5p. The miRNA-31-5p mimic suppressed and the inhibitor promoted SP-induced autophagy. Furthermore, N-Acetyltransferase 8 Like (NAT8L) was a target gene of miRNA-31-5p and knockdown of NAT8L inhibited the autophagic levels of PAECs. In vivo, SP treatment decreased miRNA-31-5p and increased NAT8L levels, which was reversed by the knockdown of GAS5. The downregulation of GAS5 abolished the stimulatory role of SP in PAECs of CTEPH rats. In conclusion, GAS5 promoted SP-induced autophagy through miRNA-31-5p/NAT8L signaling pathways in vitro and in vivo and GAS5 may be a promising molecular marker for therapies of CTEPH.

Protective role of Achyranthes bidentata polysaccharides against chondrocyte extracellular matrix degeneration through lncRNA GAS5 in osteoarthritis.

Achyranthes bidentata polysaccharides (ABPS) is an active ingredient of the flowering plant Achyranthes bidentata that has been previously reported to be effective for the treatment of osteoarthritis (OA). However, the underlying molecular mechanism remain to be fully clarified. Emerging studies have shown that the long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) is involved in the pathogenesis of OA. Therefore, the present study aimed to investigate the potential mechanism of ABPS by focusing on its effects on the regulation of chondrocyte extracellular matrix (ECM) homeostasis, with particular emphasis on lncRNA GAS5. In the present study, the modified Hulth method was used to construct OA rats, which were gavaged with 400 mg/kg ABPS for 8 weeks. Histopathological changes in cartilage and subchondral bone were evaluated by hematoxylin-eosin staining and Safranin O-fast green staining. In in vitro experiments, IL-1β-treated chondrocytes were infected with Lenti-lncRNA GAS5. Fluorescence in situ hybridization assay was performed to measure the expression of the lncRNA GAS5 in chondrocytes. Moreover, the relative expression level of lncRNA GAS5 in cartilage tissue and chondrocytes was detected using reverse transcription-quantitative PCR. Western blot analysis was used to detect protein expression levels of MMP-9, MMP-13, TIMP-1, TIMP-3 and type II collagen in cartilage tissue and chondrocytes. The results indicated that ABPS delayed the degradation of the ECM by chondrocytes in addition to reducing lncRNA GAS5 expression both in vivo and in vitro. Furthermore, silencing of lncRNA GAS5 expression in IL-1β-treated chondrocytes downregulated the protein expression of MMP-9 and MMP-13 whilst upregulating the expression of tissue inhibitor matrix metalloproteinase (TIMP)-1, TIMP-3 and type II collagen. To conclude, the present study provides evidence that ABPS can inhibit the expression of lncRNA GAS5 in chondrocytes to regulate the homeostasis of ECM, which in turn may delay the occurrence of cartilage degeneration during OA.

Level of LncRNA GAS5 and Hippocampal Volume are Associated with the Progression of Alzheimer's Disease.

PurposeWe evaluated the diagnostic value of long non-coding RNA growth arrest-specific transcript 5 (GAS5) and its relationship with hippocampal volume in Alzheimer’s disease (AD).Patients and MethodsOne hundred and eight patients with AD and 83 healthy controls were included, and demographic data, biochemical parameters, GAS5 levels, and hippocampal volume were recorded. Chi-squared tests or independent sample t-tests were used to compare the baseline characteristics, relative expression of GAS5, and hippocampal volume. Correlations between variables were determined using Spearman’s rank correlation test. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic value of GAS5 and total hippocampal volume in AD.ResultsThe levels of GAS5 were significantly upregulated in patients with AD compared with those in controls and were negatively correlated with MMSE score. There were differences in left hippocampal volume, right hippocampal volume, and total hippocampal volume between the two groups. Total hippocampal volume was positively correlated with MMSE score and negatively correlated with GAS5 expression in patients with AD. The area under the curve (AUC) of for GAS5 expression was 0.831, the sensitivity was 61.1%, and the specificity was 95.2%. The AUC of the combined total hippocampal volume was 0.891, the sensitivity was 74.1%, and the specificity was 92.8%.ConclusionThe results suggested that GAS5 may be an excellent indicator of AD progression alone or in combination with hippocampal volume.

LncRNA growth arrest specific transcript 5 inhibits the growth of pituitary neuroendocrine tumors via miR-27a-5p/cylindromatosis axis

ABSTRACT The long noncoding RNA growth arrest-specific transcript 5 (GAS5) has been reported to function as a suppressor in many cancers. However, the role and mechanism of lncRNA GAS5 in pituitary neuroendocrine tumors (PitNETs) remain unclear. Here, we found that lncRNA GAS5 and cylindromatosis (CYLD) expression was downregulated in invasive PitNET tissues and was negatively correlated with miR-27a-5p expression. LncRNA GAS5 overexpression inhibited proliferation of PitNETs cell line MMQ and GH3 cells and induced cell apoptosis, simultaneously, inhibited miR-27a-5p expression and increased CYLD expression. Moreover, miR-27a-5p mimic significantly decreased the luciferase activities of lncRNA GAS5 and CYLD luciferase reporter vector and downregulated CYLD expression, while miR-27a-5p inhibitor increased the expression of CYLD in MMQ and GH3 cells. Furthermore, RNA-immunoprecipitation assay revealed the direct binding between lncRNA GAS5 and miR-27a-5p. Additionally, miR-27a-5p mimic or silenced CYLD attenuated the effect of lncRNA GAS5 on MMQ and GH3 cell proliferation. In vivo lncRNA GAS5 overexpression inhibited GH3 cell tumor growth, while miR-27a-5p mimic or silenced CYLD attenuated the effect of lncRNA GAS5 on GH3 cell tumor growth. These results suggest that lncRNA GAS5 acts as an endogenous sponge by binding miR-27a-5p to increase the expression of its target gene CYLD, thereby inhibits PitNETs cell proliferation and tumor growth.

LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis

AbstractDiabetic cataract (DC) is a major ocular complication secondary to diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important event in DC progression. Long non-coding RNAs (lncRNAs) and microRNAs are involved in various biological processes and disorders. The aim of this study was to investigate the roles of lncRNA growth arrest-specific transcript 5 (GAS5) and microRNA-204-3p (miR-204-3p) deregulation in the pathogenic mechanism of high glucose (HG)-stimulated LECs. The results show that GAS5 was up-regulated, whereas miR-204-3p was down-regulated in anterior lens capsule tissues of DC patients and in HG-treated LECs compared to their controls, respectively. Functional experiments suggest that the lentivirus-mediated depletion of GAS5, as well as overexpression of miR-204-3p, suppressed migration and EMT in HG-treated LECs. Further mechanistic studies revealed that lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta (TGFBR1) has a regulatory role in the process. Collectively, we demonstrated that dysregulation of GAS5 affects lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis. The current findings may provide new insights into the molecular mechanisms of DC development.Under high-glucose conditions, LECs obtain characteristics of mesenchymal cells such as high migratory capacity and invasiveness, which is the foundational basis for DC progression. The authors demonstrated that lncRNA GAS5 facilitates high glucose-induced lens epithelial cell migration and epithelial-to-mesenchymal transition by regulating the miR-204-3p/TGFBR1 axis. This study, therefore, provides novel insights into the pathogenesis of DCs.

LncRNA GAS5 positively regulates IL-10 expression in patients with generalized myasthenia gravis.

IntroductionLncRNA growth arrest‐specific transcript 5 (GAS5) has been proven to be involved in autoimmune diseases. Rheumatoid arthritis is a type of autoimmune disease that may affect myasthenia gravis (MG) patients. However, its direct role in MG is unknown.MethodsOur study included 62 generalized MG patients. GAS5 expression was analyzed with real‐time quantitative RT‐PCR (qRT‐PCR). The interaction between GAS5 and interleukin 10 (IL‐10) was explored in overexpressed cells using real time quantitative polymerase chain reactions (RT‐qPCRs) and western blot. The correlation of GAS5 and IL‐10 was analyzed using Pearson's correlation analysis. The diagnostic value of GAS5 for MG was analyzed using receiver operating characteristic (ROC) curve analysis.ResultsGAS5 and IL‐10 mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in MG patients than healthy controls. Downregulated GAS5 effectively distinguished MG patients from healthy controls. GAS5 expression was positively correlated with IL‐10 expression in both MG patients and healthy controls. GAS5 overexpression significantly upregulated IL‐10 expression in PBMCs derived from both MG patients and healthy controls.ConclusionLncRNA GAS5 may improve generalized MG by positively regulating IL‐10 expression.

LncRNA GAS5 suppresses ovarian cancer progression by targeting the miR-96-5p/PTEN axis.

BackgroundLong non-coding RNAs (lncRNAs) play critical roles in the occurrence and progression of various tumors, including ovarian cancer (OC). The lncRNA growth arrest-specific transcript 5 (GAS5) has been shown to be an important modulator in the growth and metastasis of OC cells. Our previous studies confirmed that GAS5 was down-regulated in OC; however, the potential underlying molecular mechanism underlying has not yet been elucidated.MethodsWe screened the Gene Expression Profiling Interactive Analysis (GEPIA) database for the expression of the lncRNA GAS5 in OC. Cell Counting Kit-8 (CCK-8), transwell assay, colony formation assay, flow cytometry analysis, and western blotting were applied to determine the various functions of GAS5 in OC progression. The competing endogenous RNA (ceRNA) mechanism was verified through bioinformatics analysis, dual-spectral luciferase reporter gene assay, and RNA immunoprecipitation assay (RIPA). Finally, the expression interactions between microRNA-96-5p, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and GAS5 were measured.ResultsOur results demonstrated decreased expression levels of GAS5 and PTEN in OC samples and cell lines, while miR-96-5p was up-regulated when compared with the controls. GAS5 overexpression could significantly reduce OC cell proliferation and invasion ability via suppression of miR-96-5p expression. Moreover, GAS5 could influence the PTEN/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.ConclusionsOur study identified GAS5 as a ceRNA that can regulate the PTEN/AKT/mTOR axis by sponging miR-96-5p in OC.

Long‑chain non‑coding RNA GAS5 promotes cell autophagy bymodulating the miR‑181c‑5p/ATG5 and miR‑1192/ATG12 axes.

The main aim of the present study was to explore the role of long-chain non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in macrophage autophagy. Firstly, the expression of lncRNA GAS5 during cell starvation or following treatment with 3-methyladenine was determined using reverse transcription-quantitative PCR (RT-qPCR). Additionally, fluorescent in situ hybridization (FISH) assay was utilized to determine the localization of the expression of lncRNA GAS5 in RAW264.7 cells. In vitro cell models were established through the transfection of LV5-lncRNA GAS5 (LV5-GAS5) or LV3-shRNA-lnc GAS5 (sh-GAS5), in order to overexpress or knockdown lncRNA GAS5 expression in RAW264.7 cells. The potential target microRNAs (miRNAs/miRs) of lncRNA GAS5 were analyzed using bioinformatics. The formation of autophagic bodies was detected with the use of laser confocal and transmission electron microscopy. Dual-luciferase reporter assay was performed to determine the target specificities of miR-181c-5p or miR-1192 to lncRNA GAS5 and autophagy-related gene (ATG) or ATG12. The mRNA levels of miR181c-5p, miR-1192, as well as ATG5 and ATG12 were detected using RT-qPCR. The protein levels of microtubule-associated proteins 1A/1B light chain 3B (LC3), p62, ATG5 and ATG12 were measured using western blot analysis. It was revealed that lncRNA GAS5 expression in RAW264.7 macrophages increased significantly during starvation-induced autophagy, and that lncRNA GAS5 overexpression was able to markedly promote the formation of autophagic bodies. Bioinformatics analysis demonstrated that miR-181c-5p and miR-1192 were potential targets of lncRNA GAS5, which was further confirmed by RT-qPCR, western blot analysis and the dual-luciferase reporter assay. Finally, it was confirmed that lncRNA GAS5 promoted autophagy by sponging miR-181c-5p and miR-1192, and upregulating the expression levels of the key autophagic regulators, ATG5 and ATG12. On the whole, the present study demonstrates that total, lncRNA GAS5 promotes macrophage autophagy by targeting the miR-181c-5p/ATG5 and miR-1192/ATG12 axes.

Association between long non-coding RNA (lncRNA) GAS5 polymorphism rs145204276 and cancer risk.

ObjectiveThe long non-coding RNA (lncRNA) growth arrest‑specific transcript 5 (GAS5) plays an important role in various tumors, and an increasing number of studies have explored the association of the GAS5 rs145204276 polymorphism with cancer risk with inconclusive results.MethodsPubMed, Medline, EMBASE, Cochrane databases, and Web of Science were searched, and nine studies involving 6107 cases and 7909 controls were deemed eligible. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the relationship between rs145204276 and cancer risk in six genetic models.ResultsThe pooled results suggest that the variant allele del was not associated with overall cancer risk. However, the subgroup analysis showed that allele del was significantly associated with a 22% decreased risk of gastrointestinal cancer (OR = 0.78, 95% CI: 0.72–0.85). Both sensitivity analyses and trial sequential analyses (TSA) demonstrated that the subgroup results were reliable and robust. Moreover, False-Positive Report Probability (FPRP) analysis indicated that the results had true significant correlations.ConclusionThese findings provide evidence that the GAS5 rs145204276 polymorphism is associated with the susceptibility to gastrointestinal cancer. Further studies with different ethnicities and larger sample sizes are warranted to confirm these results.

Acinetobacter baumannii up-regulates LncRNA-GAS5 and promotes the degradation of STX17 by blocking the activation of YY1

ABSTRACT Acinetobacter baumanniitriggers autophagy, affects the degradation of autophagy, and causes severe inflammatory injury. LncRNA growth arrest-specific transcript 5 (LncRNA-GAS5) and Yin and Yang 1 (YY1) are known to play an important role in the regulation of autophagy, however, the precise role of LncRNA-GAS5 and YY1 in the damage to autophagy caused by Acinetobacter baumanniiremains unclear. The aim of this study was to investigate the role of LncRNA-GAS5 and YY1 in the regulation of autophagy induced by Acinetobacter baumannii. We found that LncRNA-GAS5 was up-regulated following infection with Acinetobacter baumannii, thus resulting in the degradation of STX17, autophagy disorders, and the aggravated replication of Acinetobacter baumannii. We also analyzed the mechanism of interaction between LncRNA-GAS5 and YY1 and found that YY1 regulated its expression in a negative manner by binding to the promoter of LncRNA-GAS5. LncRNA-GAS5 and YY1 had opposite effects on the expression of STX17, this process maintained the stable expression of STX17. Following Acinetobacter baumannii infection, YY1 was down regulated and then separated from the binding region of LncRNA-GAS5, thus resulting in the activation of LncRNA-GAS5 transcription and reduction in STX17 protein expression. Finally, we infected LncRNA-GAS5 knockdown mice with Acinetobacter baumannii, the expression levels of IFN-β in the lungs increased significantly, this alleviated lung injury. In conclusion, our work demonstrated the mechanism by which Acinetobacter baumannii infection can cause the degradation of STX17. We also demonstrated that LncRNA-GAS5 may be a potential therapeutic target for the treatment of lung injury induced by Acinetobacter baumannii.

Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway.

Background:Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear.Methods:The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism.Results:In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway.Conclusion:LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.