Circulating long non‐coding RNA GAS5 and SOX2OT as potential biomarkers for diagnosis and prognosis of non‐small cell lung cancer
51
Citation
35
Reference
10
Related Paper
Citation Trend
Abstract:
Early diagnosis of non-small cell lung cancer (NSCLC) is essential for patient treatment and prognosis. Long noncoding RNA (lncRNA) have potential roles in tumor initiation and differentiation. The objective of this study was to investigate whether the circulating lncRNA, growth arrest-specific transcript 5 (GAS5) and SOX2 overlapping transcript (SOX2OT), could be used as noninvasive biomarkers for NSCLC diagnosis. Moreover, we aimed at evaluating the association between lncRNA and the clinicopathological features of NSCLC in order to predict the cancer prognosis. The results showed significant downregulation of GAS5 expression and upregulation of SOX2OT in NSCLC patients compared with controls (P < 0.001). Furthermore, the expression level of GAS5 was declined in stage IV of NSCLC, but SOX2OT expression was increased sharply in stages III and IV. The expression levels of lncRNAs were used to distinguish NSCLC patients from control with an area under curve of 0.81 (sensitivity 82.5% and specificity 80%) for GAS5 and 0.73 (sensitivity 76.3% and specificity 78.6%) for SOX2OT. The combination of GAS5 and SOX2OT showed differentiation NSCLC patients from controls with increased sensitivity (83.8) and specificity (81.4). In conclusion, the newly developed diagnostic panel involving of circulating GAS5 and SOX2OT could be perfect biomarker for diagnosis and prognosis of NSCLC.Keywords:
GAS5
Cite
Abstract Background It is well-known that long non-coding RNAs (lncRNAs) play essential roles in cancer development and progression. This study aimed to assess the potential prognostic value of specific lncRNAs in breast and gynecologic cancers. Methods PubMed, EMBASE, Cochrane library and TCGA databases were systematically searched from inception to January, 2019, and identified according to eligibility criteria. A random-effects model was adopted to calculate combined hazard ratios to explore the association between specific lncRNA expression level and survival in breast and gynecologic cancers. Subgroup and publication bias analyses were also conducted. Results 111 studies encompassing nearly 20000 participants and 25 lncRNAs were included in the current study. Of the listed lncRNAs, we identified 3 lncRNAs significantly associated with both overall survival (OS) and disease-free survival (DFS) in breast and gynecologic cancers, indicating that they might act as promising prognostic biomarkers in clinical applications. Specifically, HOTAIR and PVT1 had a negative impact on survival outcome, while GAS5 was associated with better prognosis. Further subgroup analyses identified HOTAIR as a biomarker for the poor survival whether in an Asian population or in European and American populations and GAS5 as a biomarker for the relatively good prognosis of both breast and gynecologic cancers. Conclusions We here highlight that abnormal expression of 3 lncRNAs, including HOTAIR, GAS5, PVT1 might significantly affect the survival of breast and gynecologic cancer patients and serve as novel prognostic biomarkers for breast and gynecologic cancers.
GAS5
HOTAIR
PVT1
Cite
Citations (0)
Objective To evaluate the effect of treating lung cancer through bronchial artery medication(drug treatment).Method Total 16 patients with lung cancer treated by bronchial artery infusion(BAI),and the changes of the tumor diameter,alleviation of clinical symptoms and complications following infusion were observed.Results The diameter of tumor shrunk to be smaller after BAI,most of the clinical symptoms were also alleviated and no major complication occured.Conclusion The effect and the safety are good after treating lung cancer with BAI.
Bronchial artery
Cite
Citations (0)
Background: It has been reported that lncRNA growth arrest-specific transcript 5 (GAS5) interacts with miR-21, which plays critical roles in osteoporosis. The involvement of GAS5 in osteoporosis was investigated in this study. Methods: Expression levels of GAS5 and miR-21 in plasma of both osteoporosis patients and healthy controls were determined by RT-qPCR. Diagnostic values of GAS5 and miR-21 for osteoporosis were analyzed by ROC curve analysis. Overexpression experiments were used to assess the interactions between GAS5 and miR-21. The roles of GAS5 and miR-21 in the apoptosis of osteoclasts were investigated by cell apoptosis assay. Results: The present study aimed to investigate the roles of GAS5 in osteoporosis. The results showed that GAS5 was upregulated, while miR-21 was downregulated in plasma of osteoporosis patients. Expression levels of GAS5 and miR-21 were inversely correlated across plasma samples from osteoporosis patients but not the plasma samples from the controls. Altered expression of GAS5 and miR-21 distinguished osteoporosis patients from the controls. In osteoclasts, overexpression of GAS5 led to downregulation of miR-21, while overexpression of miR-21 did not affect the expression of GAS5. Overexpression of GAS5 led to promoted apoptosis of osteoclasts, while overexpression of miR-21 led to suppressed apoptosis of osteoclasts. In addition, overexpression of miR-21 attenuated the enhancing effects of overexpressing GAS5 on cell apoptosis. Conclusion: GAS5 is upregulated in osteoporosis and may downregulate miR-21 to promote the apoptosis of osteoclasts. Keywords: osteoporosis, GAS5, miR-21, apoptosis
GAS5
Cite
Citations (28)
Background: Exosomes are microvesicles that are recently discovered in intercellular communication especially between tumor cells as lung cancer that are important for tumor development and progression. Objectives: Examine the diagnostic role of serum exosomal LncRNA in lung cancer among Egyptian population. Methods: Lung cancer characteristic exosomal RNA-based biomarker Lnc-RNA-RP11-510M2.10 was selected based on bioinformatic methods, followed by RT-qPCR validation of their expression in serum of 20 patients with lung cancer and 10 healthy volunteers. Results: serum exosomal Lnc-RNA-RP11-510M2.10 showed a significant negative association with lung cancer patients in comparison to patients with healthy persons (p<0.001). Conclusion: Lnc-RNA-RP11-510M2.10 could be used as diagnostic and prognostic biomarker tools for lung cancer.
Cite
Citations (1)
The long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) seems to be involved in the regulation of mediators of tissue injury, in particular matrix metalloproteinases (MMPs), implicated in the pathogenesis of inflammatory bowel disease (IBD). We investigated the role of GAS5 in regulating MMP2 and MMP9 expression in pediatric patients with IBD and in vitro.In total, 25 IBD patients were enrolled: For each patient paired inflamed and non-inflamed biopsies were collected. RNA was extracted and GAS5, MMP2, and MMP9 were quantified by TaqMan assay. The expression of GAS5 and MMPs was also determined in the human monocytic THP1 cells differentiated into macrophages and stimulated with lipopolysaccharide (LPS). The function of GAS5 was assessed by overexpressing the lncRNA and evaluating the MMPs levels.Real-time PCR results demonstrated a downregulation of GAS5 and an upregulation of both MMPs in inflamed tissues. In vitro data confirmed the trend observed in patients for the three genes: The stimulation with LPS promoted a downregulation of GAS5 while an increase of MMPs was observed. Overexpression experiments showed that higher levels of GAS5 lead to a decrease of both enzymes.These results provide new information about the role of GAS5 in IBD: The lncRNA could mediate tissue damage by modulating the expression of MMPs.
GAS5
MMP2
MMP9
Cite
Citations (33)
Long noncoding RNAs (lncRNAs) have been illustrated as vital molecules in regulating human cancer by emerging evidence. LINC00163 is a novel lncRNA without functional definition. In this study, we investigated its role in the tumorigenesis of lung cancer. The results showed that LINC00163 level was significantly downregulated in lung cancer tissues and cell lines by bioinformatics and qRT-PCR analyses. Notably, we observed that LINC00163 expression was lower in metastatic tissues than in non-metastatic cases. Furthermore, higher expression of LINC00163 in patients with lung cancer predicted better prognosis. Gain-of-function assays illustrated that upregulation of LINC00163 dramatically suppressed the proliferation, migration and invasion of lung cancer cells in vitro, whereas promoting apoptosis. Consistently, LINC00163 overexpression impaired tumor propagation in vivo. Mechanical study revealed that LINC00163 recruited ARID1A to the promoter of TCF21 and initiated its expression. In conclusion, we concluded that LINC00163/ARID1A/TCF21 regulatory loop modulated the development of lung cancer, providing a new insight on the mechanism underlying lung cancer progression.
Cite
Citations (30)
Abstract Background Long noncoding RNA (LncRNA) played a vital role in pathophysiology of cardiovascular diseases. However, its role in the diagnosis of atrial fibrillation (AF) remains unknown. The aim of this study is to identify the diagnostic value of lncRNA GAS5 for AF patients.Methods Four lncRNAs (NEAT1, GAS5, UCA1, and TUG1) were selected as potential biomarkers of AF. The circulating expression of lncRNAs were measured by qRT-PCR. Receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were applied to assess their diagnostic value for AF.Results In screening trial, LncRNA GAS5 was down-regulated in AF patients, with no significant differences in other three lncRNAs. Then a total of 128 participants were enrolled including 85 AF patients and 43 controls. Circulating levels of GAS5 in AF patients were remarkably reduced compared with controls ( P <0.001). The AUC was 0.858, with 81.2% sensitivity and 86.0% specificity. Further, the downregulation of GAS5 was more significant in persistent rather than paroxysmal AF. Correlation analysis showed that GAS5 was negatively correlated with CHA2DS2-VASc score and several echocardiography indexes.Conclusions Circulating lncRNA GAS5 is a potential biomarker for AF diagnosis and may prognose AF progression and stroke risk.
GAS5
Diagnostic biomarker
Cite
Citations (0)
Renal fibrosis is at the core of various renal diseases, including diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) are known players in the regulation of renal fibrosis. However, their expression and function in DKD still need to be elucidated. The purpose of this study was to assess how lncRNA GAS5 regulates fibrosis and its mechanism in TGF-β1-treated renal proximal tubular cell.In this study, the lncRNA GAS5 was upregulated in both TGF-β1-treated HK-2 cells and the kidneys of HDF/STZ mice. Knockdown of GAS5 relieved renal tubular epithelial fibrosis. This effect was mediated by the downregulation and functional inactivation of miR-96-5p. Furthermore, miR-96-5p was downregulated in DKD mice, and this downregulation attenuated the repression of FN1(fibronectin, FN) and led to its upregulation. The decrease in miR-96-5p was partially attributed to the miRNA-sponge action of GAS5.Our research demonstrates that knockdown of lncRNA GAS5 leads to antifibrosis by competitively binding miR-96-5p, which inhibits the expression of FN1. These results indicate that targeting lncRNA GAS5 may be a promising therapeutic strategy for preventing DKD.
GAS5
Competing Endogenous RNA
Cite
Citations (48)
It has been reported that lncRNA GAS5 can inhibit LPS-induced inflammation, indicating its involvement in sepsis. We observed the downregulation of GAS5 in plasma of sepsis patients. In addition, expression levels of GAS5 were positively correlated with the expression levels of miR-214. In cardiomyocytes, overexpression of GAS5 upregulated the expression of miR-214, while its knockdown resulted in decreased expression levels of miR-124. Methylation-specific PCR (MSP) revealed that GAS5 negatively regulated the methylation of miR-124. Cell apoptosis showed that overexpression of GAS5 and miR-214 suppressed the apoptosis of cardiomyocytes induced by LPS. In addition, overexpression of miR-214 also reduced the enhancing effects of silencing of GAS5 on cell apoptosis. Therefore, GAS5 may upregulate miR-214 through methylation pathway to inhibit the apoptosis of cardiomyocytes in sepsis.
GAS5
Cite
Citations (14)
Immunotherapy, represented by immune checkpoint inhibitors (ICI), is transforming the treatment of cancer. However, only a fraction of patients show response to ICI, and there is an unmet need for biomarkers that will identify patients more likely to respond to ICI. Here we report that the ICI response prediction biomarker tumor mutational burden (TMB) shows significant sex differences. TMB's predictive power is significantly better for female than for male lung cancer patients. Receiver operating characteristic curve analysis was performed and the area under the curve (AUC) was reported to evaluate the predictive power of TMB in lung cancer ICI response. Hazard ratios (HR) of TMB-high vs. TMB-low patients were compared between male and female patients. Both AUC and HR differences between female and male are significant in all available independent lung cancer datasets. However, the AUC of programmed death ligand 1 (PD-L1) expression does not show a difference between female and male, suggesting TMB, but not PD-L1 expression has a better predictive power for female than for male lung cancer patients. Our study suggests significant sex differences in the performance of TMB in ICI response prediction. Future development of ICI biomarker should consider sex differences and special efforts should be paid to improve the performance of ICI predictive biomarkers for male lung cancer patients.
Predictive marker
Cite
Citations (73)