Analysis of Long Noncoding RNAs in Aila-Induced Non-Small Cell Lung Cancer Inhibition.
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ABSTRACT:
SUBMITTER: Chen L
PROVIDER: S-EPMC8255921 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Identification of novel effective early diagnostic biomarkers may provide alternative strategies to reduce the mortality for non-small cell lung cancer (NSCLC) patients. Circulating long non-coding RNAs (lncRNAs) have emerged as a new class of promising cancer biomarkers. Our study aimed to identify circulating lncRNAs for diagnosing NSCLC. A total 528 plasma samples were continuously collected and allocated to four progressive phases: discovery, training, verification, and expansion phases. The expression of candidate lung cancer related lncRNAs were detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We identified a 4-lncRNA panel (RMRP, NEAT1, TUG1, and MALAT1) that provided a high diagnostic value in NSCLC (AUC = 0.86 and 0.89 for training and verification phase, respectively). Subgroup analyses showed that the 4-lncRNA panel had a sensitivity of 78.95% [95% confidence interval (CI) = 62.22%-89.86%] in stage I-II patients and 75.00% (95% CI = 52.95%-89.40%) in patients with small tumor size (≤3cm). Notably, the sensitivity of 4-lncRNA panel was significantly higher than that of routine protein panels in adenocarcinoma (CEA, CA125, and CYFRA21-1, 86.30% vs. 73.96%). Adding 4-lncRNA to protein markers significantly improved the diagnostic capacity in both adenocarcinoma (AUC=0.85, 95% CI = 0.78-0.91) and squamous cell carcinoma (AUC=0.93, 95% CI = 0.86-0.97). In conclusion, we identified a plasma 4-lncRNA panel that has considerable clinical value in diagnosing NSCLC. The 4-lncRNA panel could improve the diagnostic values of routine tumor protein markers in diagnosing NSCLC. Circulating lncRNAs could be used as promising candidates for NSCLC diagnosis.
| S-EPMC7793881 | biostudies-literature
Project description:Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The overall 5-year survival rate of patients is extremely low and to find a new marker is urgently needed. Numerous studies indicate that long noncoding RNAs (lncRNAs) abnormally express in cancers. However, the results have been disputed, especially in the aspects of tumor prognosis. Therefore, we performed this meta-analysis to systematically summarize the relationship between lncRNAs expression and NSCLC. A total of 34 eligible studies including 30 on overall survival, 10 on progression-free survival and 23 on clinicopathological features were identified from the databases. Our results indicated that the levels of lncRNAs were associated with the overall survival (OS; hazard ratios [HR], 1.43; 95% confidence interval [95% CI], 1.17-1.76; P < 0.001). However, there was no relationship between lncRNAs and progression-free survival (PFS; hazard ratios [HR], 1.55; 95% confidence interval [95% CI], 0.91-2.63; P = 0.11). Moreover, lncRNAs were related to lymph node metastasis (odds ratios [OR], 1.70; 95% confidence interval [95% CI], 1.03-2.80; P = 0.04), while no association was observed with other characteristics. In conclusion, our present meta-analysis indicated that lncRNAs transcription levels may serve as a promising marker for prognosis of patients with NSCLC.
| S-EPMC5354806 | biostudies-other
Project description:Increasing the efficiency of early diagnosis using noninvasive biomarkers is crucial for enhancing the survival rate of lung cancer patients. We explore the differential expression of non-small cell lung cancer (NSCLC)-related long noncoding RNAs (lncRNAs) in urinary exosomes in NSCLC patients and normal controls to diagnose lung cancer. A differential expression analysis between NSCLC patients and healthy controls was performed using microarrays. Gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict potential functions of lncRNAs in NSCLC. quantitative real-time PCR (QT-PCR) was used to verify microarray results. A total of 640 lncRNAs (70 up- and 570 down-regulated) were differentially expressed in NSCLC patients in comparison to healthy controls. Six lncRNAs were detected by QT-PCR. GO term and KEGG pathway analyses showed that differential lncRNAs were enriched in cellular component organization or biogenesis, as well as other biological processes and signaling pathways, such as the PI3K-AKT, FOXO, p53, and fatty acid biosynthesis. The differential lncRNAs in urinary exosomes are potential diagnostic biomarkers of NSCLC. The lncRNAs enriched in specific pathways may be associated with tumor cell proliferation, tumor cell apoptosis, and the cell cycle involved in the pathogenesis of NSCLC.
| S-EPMC8521532 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) are widely dysregulated in cancer, yet their functional roles in cancer hallmarks remain unclear. We employ pooled CRISPR deletion to perturb 831 lncRNAs detected in KRAS-mutant non-small cell lung cancer (NSCLC) and measure their contribution to proliferation, chemoresistance, and migration across two cell backgrounds. Integrative analysis of these data outperforms conventional "dropout" screens in identifying cancer genes while prioritizing disease-relevant lncRNAs with pleiotropic and background-independent roles. Altogether, 80 high-confidence oncogenic lncRNAs are active in NSCLC, which tend to be amplified and overexpressed in tumors. A follow-up antisense oligonucleotide (ASO) screen shortlisted two candidates, Cancer Hallmarks in Lung LncRNA 1 (CHiLL1) and GCAWKR, whose knockdown consistently suppressed cancer hallmarks in two- and three-dimension tumor models. Molecular phenotyping reveals that CHiLL1 and GCAWKR control cellular-level phenotypes via distinct transcriptional networks. This work reveals a multi-dimensional functional lncRNA landscape underlying NSCLC that contains potential therapeutic vulnerabilities.
| S-EPMC9903773 | biostudies-literature
Project description:Long noncoding RNA differentiation antagonizing nonprotein coding RNA (lncRNA-DANCR) is associated with poor prognosis in multiple cancers, and promotes cancer stemness and invasion. However, the exact mechanisms by which DANCR promotes non-small cell lung cancer (NSCLC) remain elusive. In this study, we determined that DANCR knockdown (KD) impeded cell migration and reduced stem-like characteristics in two NSCLC cell lines, A549 and H1755. Wnt signaling was shown to promote NSCLC proliferation, stemness, and invasion; therefore, we hypothesized that DANCR may regulate these activities through induction of the Wnt/β-catenin pathway. DANCR KD reduced β-catenin signaling and protein expression, and decreased the expression of β-catenin gene targets c-Myc and Axin2. One of the well-defined functions of lncRNAs is their ability to bind and inhibit microRNAs. Through in silico analysis, we identified tumor suppressor miR-216a as a potential binding partner to DANCR, and confirmed this binding through coimmunoprecipitation and luciferase-reporter assays. Furthermore, we show that DANCR-induced β-catenin protein expression may be blocked with miR-216a overexpression. Our findings illustrate a role of DANCR in NSCLC migration and stemness, and suggest a novel DANCR/miR-216a signaling axis in the Wnt/β-catenin pathway.
| S-EPMC7764320 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. LncRNA IRAIN has been verified that it is related to acute myeloid leukemia (AML) and breast cancer. However, there was no study to clarify whether it is involved in non-small cell lung cancer (NSCLC). Here, we demonstrated IRAIN as a tumor promoter in NSCLC. Its expression level was remarkably upregulated in NSCLC tissues and connected with tumor size and smoking status. Knockdown of IRAIN suppressed NSCLC cells proliferation in vitro. These data identify IRAIN as a novel promoting gene, which plays a vital role in tumorigenesis of NSCLC.
| S-EPMC4680357 | biostudies-literature
Project description:Non-small cell lung cancer (NSCLC) is the primary subtype of lung cancer. Long non-coding RNAs (lncRNAs) have been reported to serve prominent roles in cancer progression. However, the expression patterns and potential roles of lncRNAs in NSCLC remain to be elucidated. In the present study, four public datasets were analyzed to identify differentially expressed lncRNAs (DElncs) in NSCLC. A further dataset, GSE19188, was analyzed to validate the findings. A total of 38 upregulated and 31 downregulated lncRNAs were identified in NSCLC, compared with samples from healthy controls. Among these, 12 lncRNAs were associated with the progression of NSCLC, and dysregulated between high grade (stage III and IV) and low grade (stage II) NSCLC samples. Moreover, dysregulation of lncRNA-SIGLEC17P, GGTA1P, A2M-AS1, LINC00938, GVINP1, LINC00667 and TMPO-AS1 was associated with overall survival time in patients with NSCLC. Co-expression analyses, combined with the construction of protein-protein interaction networks, were performed to reveal the potential roles of key lncRNAs in NSCLC. The present study revealed a series of lncRNAs involved in the progression of NSCLS, which may serve as novel biomarkers for the disease.
| S-EPMC6607379 | biostudies-literature
Project description:Background:The further progression of credible expression profiling analysis of genes continues to expand our understanding of the biological characteristics in lung cancer. In this study, RNA sequencing (RNA-Seq) was used to contrast the transcriptomics profiling of small cell lung cancer (SCLC) that acquired partial response (PR) and stable disease (SD)/progressive disease (PD) after first-line chemotherapy. We aimed to illuminate the underlying mechanisms of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in the efficacy of SCLC first-line chemotherapy. Methods:Six male patients (mean age, 64.2 years) with SCLC were enrolled in this study. RNA-Seq was executed on the tumor tissues from 3 patients with PR outcome and 3 patients with SD or PD therapeutic effect after first-line chemotherapy. Results:RNA-Seq generated 26.67×106 (±8.7×106) reads in SCLC tissues [mean (±standard deviation)]. Analysis revealed that 64 lncRNAs had higher expression and 194 had lower expression in the PR group ?2-fold (P<0.05). Three downregulated genes in the PR group [HOXA-AS3, cancer susceptibility 9 (CASC9), and KEGG] could have a role in the insensitivity of SCLC. A total of 1,303 differential miRNAs were defined between PR and the SD or PD SCLC group, while 520 miRNAs had higher expression, and 783 had lower expression in the PR group. Two lower expressed miRNAs in the PR group (miRNA 601 and miRNA 596) might be the key genes in SCLC chemotherapy insensitivity. Conclusions:The expression of 3 gene (HOXA-AS3, CASC9, and KEGG) and 2 miRNAs (miRNA 601 and miRNA 596) were markedly decreased in SCLC patients who achieved PR. They thus might be the promising candidate genes in SCLC chemotherapy insensitivity.
| S-EPMC7049041 | biostudies-literature
Project description:BACKGROUND:Aberrant expression of long non-coding RNA cancer susceptibility 15 (lncRNA CASC15) has been documented in various human tumors, and upregulation of CASC15 is closely correlated with cancer progression. However, the expression profile and potential biological functions of lncRNA CASC15 in non-small cell lung cancer (NSCLC) have not been fully characterized. METHODS:The expression levels of CASC15 were assessed by qRT-PCR in human NSCLC tissues and by in situ hybridization in NSCLC tissue microarray. The relationship between CASC15 expression and clinical parameters, as well as prognosis were analyzed and validated in TCGA NSCLC datasets. The biological functions of CASC15 were analyzed by CCK-8 assay, cell migration and invasion assay in NSCLC cell lines in vitro. In addition, a mouse xenograft model was established to evaluate the effect of CASC15 knockdown on NSCLC tumor growth in vivo. Epithelial-mesenchymal transition (EMT) related molecules were examined by western blot and immunohistochemistry staining. RESULTS:We found that CASC15 was upregulated in NSCLC tissues and cell lines. High expression levels of CASC15 were correlated with malignancies and poor survival rate in NSCLC patients. Multivariate analysis revealed that CASC15 was an independent risk factor of prognosis. In addition, we demonstrated that CASC15 knockdown inhibited NSCLC cell proliferation, migration and invasion in vitro. Xenograft model showed CASC15 knockdown significantly suppressed NSCLC tumor growth. Mechanistically, we revealed that CASC15 regulated EMT-related molecules and promoted the NSCLC progression and metastasis. CONCLUSION:In summary, our findings suggest CASC15 exhibits an oncogenic role in promoting NSCLC tumorigenesis via regulating EMT.
| S-EPMC6684884 | biostudies-other
Project description:BackgroundNon-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard.MethodsIn the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs).ResultsNEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs.ConclusionsThe observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.
| S-EPMC6417110 | biostudies-literature