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The article titled "[Retracted] Downregulation of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion in esophageal squamous cell carcinoma" has been retracted by the Editor of Oncology Letters due to concerns about the integrity of the data presented. An area of similarity was identified in the cellular data, and the western blots showed atypical and possibly anomalous protein bands. The authors were asked for an explanation but did not respond. The Editor apologizes for any inconvenience caused and thanks the concerned reader for bringing this matter to their attention. [Extracted from the article]

The present study aimed to investigate the expression and significance of the mRNA of genes associated with autophagy and long non-coding RNA (lncRNA) GAS5 in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS). The mRNA levels of microtubule-associated protein light chain 3 (LC3), Beclin1, autophagy-related gene (ATG)3, ATG5, ATG12, ATG 16 ligand 1 (ATG16L1) and lncRNA growth arrest-specific 5 (GAS5) in PBMCs from 60 patients with AS and 30 healthy controls (HC) were examined by reverse transcription-quantitative PCR. The correlations between the levels of LC3, Beclin1, ATG3, ATG5, ATG12 and ATG16L1 mRNA as well as lncRNA GAS5 levels with disease activity and laboratory parameters in patients with AS were determined by Spearman correlation analysis. In addition, the diagnostic value of lncRNA GAS5 for AS was explored through establishing a receiver operating characteristic (ROC) curve. The results indicated that, compared to the HCs, patients with AS had lower expression levels of LC3, ATG5, ATG12, ATG16L1 and lncRNA GAS5 in their PBMCs. Compared with those in patients with inactive AS, the levels of ATG5 and ATG12 were lower than those in patients with active AS. Of note, ATG5 and ATG12 mRNA levels were negatively correlated with disease activity indexes. lncRNA GAS5 was positively correlated with the expression of Beclin1, ATG3, ATG5, ATG12 and ATG16L1. The area under the ROC curve for the use of lncRNA GAS5 expression to diagnose AS was 0.808 with a 95% CI of 0.714-0.902. In conclusion, patients with AS had decreased expression of genes associated with autophagy and lncRNA GAS5. The extent of the reduction in ATG5 and ATG12 expression levels in patients with AS was correlated with the disease severity and activity. Furthermore, lncRNA GAS5 was a diagnostic indicator of AS. [ABSTRACT FROM AUTHOR]

Growth arrest-specific 5 (GAS5) is a known tumor suppressor which negatively regulates cell survival and malignancy in several cancer cell types. The present study aimed to establish the correlation between GAS5 and unc-51 like autophagy activating kinase (ULK)1/2, two key regulators of autophagy initiation in breast cancer (BC). To address this, expression levels of these genes were quantitively analyzed in BC clinical samples by performing reverse transcription-quantitative PCR. GAS5 was downregulated in BC clinical samples compared with adjacent samples and was positively correlated with ULK1/2. Detection methods including cell cycle analysis, annexin V-FITC/PI double staining and flow cytometry analysis, Transwell cell invasion assay, transfection and western blotting were used for BC cells. In MCF-7 cells, it was also observed that overexpression of GAS5 upregulated ULK1/2 protein levels without disturbing other autophagy initiation-associated proteins and inhibited cell proliferation, invasion and tumor formation. These effects were reversed by blocking autophagy with 3-methyladenine (3-MA). These results demonstrated that the suppressive effects of overexpressed GAS5 were mediated via autophagy induction, at least in part. Overexpression of GAS5 induced chemoresistance to cisplatin, which was not reversed by 3-MA-mediated inhibition of autophagy, indicating that GAS5 promotes chemosensitivity in an autophagy-independent manner. Collectively, these results indicated that GAS5 contributes to the pathogenesis of BC potentially by promoting autophagy. However, the mechanism by which GAS5 functions as a tumor suppressor in an autophagy-independent manner remains unknown. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) constitute a group of >200-nucleotide ncRNA molecules. lncRNAs regulate several cell functions, such as proliferation, apoptosis, invasion and metastasis. Meanwhile, lncRNAs are abnormally expressed in human malignancies, where they suppress or promote tumor growth. The present study focused on growth arrest-specific transcript 5 (GAS5), a well-known lncRNA that acts as a tumor suppressor but is suppressed in multiple types of cancer, including mammary carcinoma, prostate cancer, colorectal cancer, gastric cancer, melanoma, esophageal squamous cell carcinoma, lung cancer, ovarian cancer, cervical cancer, gliomas, osteosarcoma, pancreatic cancer, bladder cancer, kidney cancer, papillary thyroid carcinoma, neuroblastoma, endometrial cancer and liver cancer. Notably, GAS5 is overexpressed in liver cancer, potentially functioning as an oncogene. In the present study, the diagnostic and therapeutic roles of GAS5 in different tumors were reviewed, with a summary of the potential clinical application of the lncRNA, which may help identify novel study directions for GAS5. [ABSTRACT FROM AUTHOR]

Hyperglycemia impairs the retinal functions in patients with diabetic retinopathy (DR). Downregulation of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) expression in diabetes affects glucose intake and insulin signaling. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) mediates the regulation of endoplasmic reticulum (ER) stress and apoptosis in high glucose (HG)-treated podocytes. Therefore, the present study aimed to investigate the roles of lncRNA GAS5 and SERCA2 in retinal pigment epithelium cells exposed to HG. GAS5 expression levels were detected using reverse transcription-quantitative PCR. In addition, the expression levels of SERCA2b, ER stress-related proteins, pro-inflammatory factors and apoptotic proteins were determined by western blot analysis, ELISA or flow cytometry. The results showed that HG treatment induced ER stress in ARPE-19 human adult retinal pigment epithelial cells by upregulating the expression levels of phosphorylated (p)-protein kinase R-like ER kinase, p-eukaryotic initiation factor 2α, activating transcription factor 4 and CCAAT/enhancer-binding protein homologous protein. In addition, HG treatment induced apoptosis by increasing Bax, Bad and caspase 12, and by decreasing Bcl-2 levels expression levels. Moreover, HG treatment induced inflammation by upregulating tumor necrosis factor-α, interleukin (IL)-1β and IL-6 expression. However, GAS5 and SERCA2b overexpression significantly decreased ER stress-related apoptosis and inflammation, whereas SERCA2b knockdown significantly reversed the inhibitory effect of GAS5 on ER stress, apoptosis and inflammation. The results of the present study indicated that GAS5 may suppress ER stress-induced apoptosis and inflammation by regulating SERCA2b in HG-treated cells. These data suggested that GAS5 may serve a vital role in the pathogenesis of DR, and it may be considered a potential target for DR therapy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are recognized as critical regulators of self-renewal in human cancer stem-like cells (CSCs), which are a subpopulation of cancer cells primarily responsible for the malignant features of cancer. However, most CSC-related lncRNAs remain unidentified. The results of the present study suggested that growth-arrest-specific transcript 5 (GAS5), a tumor suppressor, exhibited increased expression and was associated with malignant features in human colorectal cancer cell HCT116-derived CSCs. Phenotypic analysis indicated that GAS5 knockdown by specific siRNA significantly decreased CSC self-renewal capacity, proliferation and migration. Moreover, GAS5 knockdown sensitized CSCs to the chemotherapeutic agents 5-fluorouracil and doxorubicin by inducing apoptosis detected by Annexin V-FITC/PI double staining. Inhibition of Nodal growth differentiation factor (NODAL) signaling, which has been reported to be protected by GAS5, presented similar chemosensitivity effects to the GAS5 knockdown results. The present study also assessed the effects of GAS5 overexpression on HCT116 cells, and revealed that overexpression of GAS5 sensitized HCT116 cells to chemotherapeutic agents, which is the opposite of the effect observed in CSCs derived from HCT116 cells. Therefore, it was hypothesized that GAS5 may function as a critical factor for maintaining stemness and that it may exert protective effects on CSCs in a NODAL-dependent manner. Collectively, the results of the present study indicate that GAS5 may be a promising therapeutic target for overcoming malignant features and chemoresistance in colorectal cancer cells. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of the long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) on proliferation, apoptosis and the inflammatory response of osteoarthritic chondrocytes (OACs) and its associated mechanism of action. Primary chondrocytes were isolated from cartilage tissues of osteoarthritis (OA) patients for subculture. GAS5 was silenced in OACs by liposome transfection. The effects of GAS5 silencing on proliferation, apoptosis, stromal metabolism and inflammatory response of OACs were analyzed. The association of GAS5 with its target microRNA-34a (miR-34a) and the downstream target gene Bcl-2 was verified by luciferase reporter assays. The results indicated that GAS5 silencing promoted the proliferation, inhibited cell apoptosis and caused G1 arrest of OACs compared with the control group (P<0.05). The expression levels of TNF-α and IL-6 in the supernatant of OACs in the si-GAS5 group were significantly lower than those of the control group (P<0.05). The results of the double luciferase reporter assays indicated that overexpression of GAS5 downregulated miR-34a and upregulated Bcl-2 levels (P<0.05) compared with the expression levels of these markers in the control group. In contrast to GAS5 overexpression, knockdown of this RNA caused a significant upregulation of miR-34a levels and a significant downregulation in the levels of Bcl-2 (P<0.05). Moreover, GAS5 overexpression could counteract the inhibition of apoptosis by overexpression of miR-34a (P<0.05). The data indicated that GAS5 participated in the development of OA by regulating the biological behavior of chondrocytes via the miR-34a/Bcl-2 axis. [ABSTRACT FROM AUTHOR]

MicroRNA-145 (miR-145) and long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) function as tumor suppressors in prostate carcinoma. The aim of the present study was to investigate the role of miR-145 and lncRNA GAS5 in prostate carcinoma. In the present study, miR-145 and lncRNA GAS5 expression levels were demonstrated to be downregulated in tumor tissues compared with adjacent healthy tissues of patients with prostate carcinoma. miR-145 and lncRNA GAS5 expression levels were found to be positively and significantly correlated in tumor tissues, but not in adjacent healthy tissues. A follow-up study revealed that low miR-145 and lncRNA GAS5 expression levels were associated with poor survival. Overexpression of miR-145 resulted in upregulated lncRNA GAS5, whereas lncRNA GAS5 overexpression or silencing did not affect miR-145 expression. Overexpression of miR-145 and lncRNA GAS5 promoted apoptosis and inhibited cell proliferation in prostate carcinoma cell lines, whereas lncRNA GAS5 knockdown had an opposite effect. In addition, lncRNA GAS5 knockdown partially attenuated the effect of miR-145 overexpression of cancer cell proliferation and apoptosis. Therefore, miR-145 may inhibit cell proliferation and induce apoptosis in human prostate carcinoma by upregulating lncRNA GAS5. [ABSTRACT FROM AUTHOR]

Nucleus pulposus cell (NPC) apoptosis serves an important role in intervertebral disc degeneration (IDD); however, the roles of long noncoding RNAs (lncRNAs) in this process remain unknown. The present study aimed to determine the effects of the lncRNA growth arrest-specific transcript 5 (GAS5) on the apoptosis of primary human NPCs derived from the intervertebral disc, and to investigate the underlying mechanisms. TargetScan was used to predict the lncRNAs targeted by microRNA-155 (miR-155). Then, NPCs were subjected to lentivirus-mediated transduction of miR-155 or GAS5. A human lncRNA and mRNA array was used to screen differentially expressed lncRNAs following miR-155 overexpression. GAS5 and miR-155 expression levels were determined by reverse transcription-quantitative polymerase chain reaction. After GAS5 overexpression, apoptosis was assessed by flow cytometry via Annexin V/propidium iodide staining. Western blotting was employed to determine the expression of apoptosis-associated proteins, including caspase-3 and B cell lymphoma 2 (Bcl-2). TargetScan indicated GAS5 had one binding site for miR-155. Following exogenous transfection of miR-155 mimics, GAS5 expression levels in NPCs were significantly decreased (P<0.05). Interestingly, miR-155 overexpression in NPCs resulted in 721 differentially expressed lncRNAs compared with the negative control group (P<0.05), including 492 and 229 upregulated and downregulated lncRNAs respectively. In addition, 18 transcripts of GAS5 exhibited a downregulated expression profile. GAS5 overexpression in NPCs resulted in enhanced caspase-3 decreased Bcl-2 expression levels; the apoptosis of NPCs was significantly increased (P<0.05). The results of the present study revealed that overexpression of lncRNA GAS5 may promotes NPC apoptosis via Bcl-2 downregulation and caspase-3 upregulation, which may be associated with miR-155. The results of the present study suggest that lncRNA GAS5-silenced NPCs, or lentivirus-mediated lncRNA GAS5 knockdown may be precise and effective therapeutic strategies in the treatment of IDD. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the expression of growth arrest-specific 5 (GAS5) and microRNA (miR)-21 in systemic lupus erythematosus (SLE), and attempted to explore their association with clinical features. CD4+ T cells were isolated from peripheral blood of healthy donors and SLE patients by magnetic-activated cell sorting. GAS5 and miR-21 expression levels in cluster of differentiation (CD)4+ T cells were measured by reverse-transcription quantitative polymerase chain reaction. The results revealed that GAS5 and miR-21 levels were significantly elevated in CD4+ T cells of patients with SLE compared with those in control subjects (P<0.05). Regarding clinical features, SLE patients with ulceration had higher GAS5 expression levels in CD4+ T cells than those without ulceration (P<0.05), and the expression of miR-21 was significantly higher in CD4+ T cells of SLE patients with low levels of complement component 3 (C3) than in those with normal levels of complement C3 (P<0.05). In conclusion, GAS5 and miR-21 in CD4+ T cells may serve as potential biomarkers for the diagnosis and monitoring of the progression of SLE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are key in carcinogenesis. The aim of the present study was to investigate the role of lncRNA GAS5 in HCC tissues and to define the role of growth arrest-specific 5 (GAS5) in the regulation of hepatoma cell proliferation, invasion and apoptosis. Quantitative polymerase chain reaction and in situ hybridization were performed to investigate the expression of GAS5 in tumor tissues and corresponding adjacent tissues from 50 patients with HCC. Low expression of GAS5 was significantly correlated with differentiation (P<0.010) and portal vein tumor thrombosis (P=0.001). Multivariate analysis indicated that GAS5 expression was an independent predictor for overall survival (P=0.017). Further experiments demonstrated that overexpression of GAS5 significantly suppressed the proliferation and invasion of hepatoma cells in vitro. Overexpression of GAS5 significantly promoted the apoptosis of hepatoma cells. In addition, it was demonstrated that GAS5 negatively regulates vimentin expression in vitro and in vivo. Notably, vimentin knockdown promoted GAS5-pcDNA3.1-inhibition of hepatoma cell proliferation. In conclusion, the present study suggests an important role of GAS5 in the molecular etiology of HCC and suggests the potential application of GAS5 in HCC therapy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have important roles in diverse biological processes, including transcriptional regulation, cell growth and tumorigenesis. The present study aimed to investigate whether lncRNA-growth arrest-specific (GAS)5 regulated bladder cancer progression via regulation of chemokine (C-C) ligand (CCL)1 expression. The viability of BLX bladder cancer cells was detected using a Cell Counting kit-8 assay, and cell apoptosis was assessed by annexin V-propidium iodide double-staining. The expression levels of specific genes and proteins were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. In addition, cells were transfected with small interfering (si)RNAs or recombinant GAS5 in order to silence or overexpress GAS5, respectively. The results of the present study demonstrated that knockdown of GAS5 expression promoted bladder cancer cell proliferation, whereas overexpression of GAS5 suppressed cell proliferation. Furthermore, knockdown of GAS5 resulted in an increased percentage of cells in S and G2 phase, and a decreased percentage of cells in G1 phase. In addition, the present study performed a hierarchical cluster analysis of differentially expressed lncRNAs in bladder cancer cells and detected that CCL1 overexpression resulted in an upregulation of GAS5, which may improve the ability of cells to regulate a stress response in vitro. Furthermore, knockdown of GAS5 expression increased the mRNA and protein expression of CCL1 in bladder cancer cells. Gain-of-function and loss-of-function studies demonstrated that GAS5 was able to inhibit bladder cancer cell proliferation, at least in part, by suppressing the expression of CCL1. The results of the present study demonstrated that GAS5 was able to suppress bladder cancer cell proliferation, at least partially, by suppressing the expression of CCL1. The results of the present study may provide a basis for developing novel effective treatment strategies against bladder cancer. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses a spectrum of diseases, including chronic obstructive bronchitis and emphysema. Pyroptosis is a unique form of inflammatory cell death mediated by the activation of caspase-1 and inflammasomes. The long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) is a well-documented tumor suppressor, which is associated with cell proliferation and death in various diseases. The aim of the present study was to evaluate whether lncRNA GAS5 is associated with the pyroptosis in COPD. To create a COPD cell model, MRC-5 cells were treated with 10 µg/ml lipopolysaccharide (LPS) for 48 h. Then the level of pro-caspase 1, caspase 1, IL-1β, IL-18, NLRP3 and cleaved gasdermin D (GSDMD) was examined by western blotting. GAS5 mRNA level was detected by qualitative PCR following LPS treatment in MRC-5 cells. Subsequently, IL-2, IL-6, IL-10 and TNF-α in MRC-5 cells was measured by ELISA. Then the proliferation ability of MRC-5 cells was detected by CCK-8. Cell death was detected by TUNEL assay. LDH release was measured using an LDH Cytotoxicity Assay kit. The Magna RIP kit was used to validate the interaction between GAS5 and miR-223-3p. The present study revealed that increased expression levels of caspase-1, IL-1β, IL-18 and cleaved GSDMD were observed in LPS-treated MRC-5 cells, indicating that pyroptosis is involved in COPD progression. Additionally, LPS induced the increase in GAS5 mRNA expression levels and the release of inflammatory factors (IL-2, IL-6, IL-10 and TNF-α), suggesting that GAS5 is implicated in pyroptosis in COPD. Furthermore, upregulation of GAS5 promoted cell death and inhibited proliferation in the MRC-5 cell line. Additionally, increased GAS5 expression significantly promoted the production of caspase-1, IL-1β, IL-18, cleaved GSDMD and NLR pyrin domain containing protein 3 (NLRP3). A dual-luciferase assay demonstrated that GAS5 could directly bind to microRNA-223-3p (miR-223-3p), and NLRP3 is a direct target of miR-223-3p. Furthermore, GAS5 reduced the expression levels of miR-223-3p, while it increased the expression levels of NLRP3. The present study concluded that lncRNA GAS5 promoted pyroptosis in COPD by targeting the miR-223-3p/NLRP3 axis, implying that GAS5 could be a potential target for COPD. [ABSTRACT FROM AUTHOR]

The aim of the present study was to detect the serum levels of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in patients with rheumatoid arthritis (RA) and healthy controls, and determine the association between the rs2067079, rs6790, and rs17359906 single-nucleotide polymorphisms (SNPs) of lncRNA GAS5 gene with RA risk in the Egyptian population. Reverse transcription-quantitative PCR and real-time PCR were used to measure the serum levels of lncRNA GAS5 and genotype the two distinct alleles at the SNP sites of lncRNA GAS5 gene in 200 patients with RA and 150 controls. The mean serum levels of lncRNA GAS5 were significantly lower in the patients with RA compared with the controls (P<0.0001), and the serum levels of lncRNA GAS5 were significantly negatively associated with erythrocyte sedimentation rate, C-reactive protein levels and anti-cyclic citrullinated peptide levels in the patients with RA. The TT genotype of rs2067079 SNP was significantly associated with a decreased risk of RA [TT vs. CC: Odds ratio (OR)=2.358; 95% confidence interval (CI), 1.114-5.131; P=0.045) and the risk of rs2067079 SNP reduced with a recessive pattern (TT vs. TC + CC: OR=2.374; 95% CI, 1.091-5.123; P=0.037). rs6790 SNP was associated with RA risk in the recessive model (AA vs. GA + GG: OR=2.55; 95% CI=1.39-5.32; P=0.02). No significant associations were noted between the rs17359906 SNP and RA risk (P>0.05) or between the lncRNA GAS5 levels and their respective genotypes at the three SNPs in patients with RA (all P>0.05). Based on the results of the present study, lncRNA GAS5 may serve as a biomarker for the early detection of RA. The TT genotype of rs2067079 SNP was significantly associated with a decreased risk of RA, and a reduced risk of rs2067079 SNP was observed with a recessive pattern. rs6790 SNP was associated with RA risk in the recessive model. [ABSTRACT FROM AUTHOR]

Osteoporosis is a severe bone disease commonly occurring in older males and postmenopausal females. Previous studies have shown that long non-coding (lnc)RNA growth arrest-specific 5 (GAS5) serves an important role in osteoporosis. However, its role is unclear and requires further exploration. The relative expression levels of GAS5 and miR-10a-3p in the serum samples of patients with osteoporosis, as well as the relative expression levels of GAS5, microRNA (miR)-10a-3p and vascular endothelial growth factor A (VEGFA) mRNA in osteoblasts, were detected by reverse transcription-quantitative PCR. ELISA and western blotting were used to detect the expression levels of VEGFA. A Matrigel angiogenesis test was used to assess the effects on angiogenesis. RNA binding interactions between GAS5/miR-10a-3p and miR-10a-3p/VEGFA were evaluated using dual-luciferase reporter assays. Furthermore, the effects of the GAS5/miR-10a-3p/VEGFA axis were investigated via ELISA, western blotting and Matrigel angiogenesis. GAS5 was significantly downregulated and miR-10a-3p was upregulated in patients with osteoporosis. Overexpression of GAS5 promoted angiogenesis. GAS5 acted as a sponge of miR-10a-3p; VEGFA was a target gene of miR-10a-3p. GAS5 induced angiogenesis by inhibiting miR-10a-3p and enhancing VEGFA expression. These results indicated that GAS5 overexpression increased angiogenesis by inhibiting miR-10a-3p, promoting the expression of VEGFA. The present study revealed a novel mechanism and provided novel targets for the clinical treatment of osteoporosis. [ABSTRACT FROM AUTHOR]