Dataset Information

Identification of Long Non-Coding RNA MIR4435-2HG as a Prognostic Biomarker in Bladder Cancer.

ABSTRACT: The abnormal expression of long non-coding RNAs(lncRNAs) is closely related to the prognosis of patients. This finding may indicate a new target for the treatment of malignant tumors. Non-muscle invasive bladder cancer (NMIBC) is the most common subtype of bladder cancer, and BCG intravesical therapy is the first-line treatment for NMIBC, but about half of NMIBC patients relapse within two years after BCG treatment. Therefore, it is necessary to screen out lncRNAs related to the prognosis and treatment of BGC-resistant patients. Here, we performed differential expression analysis of lncRNAs in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and screened MIR4435-2HG as the only BCG-response-related lncRNA. Then, the prognosis value of MIR4435-2HG was validated in several publicly available cohorts, and confirmed its prognostic value in bladder cancer of different stages. In addition, we also analyzed its genetic alterations, clinical relevance, function enrichment, and association with other biomarkers. Further validation of the expression of MIR4435-2HG might be helpful to instruct NMIBC prognosis and treatment.

SUBMITTER: Hu Z

PROVIDER: S-EPMC9408477 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Identification of Long Non-Coding RNA MIR4435-2HG as a Prognostic Biomarker in Bladder Cancer.

Hu Zhiquan Z Ma Siquan S Sun Yi Y Long Gongwei G Chen Ke K

Genes 20220817 8

The abnormal expression of long non-coding RNAs(lncRNAs) is closely related to the prognosis of patients. This finding may indicate a new target for the treatment of malignant tumors. Non-muscle invasive bladder cancer (NMIBC) is the most common subtype of bladder cancer, and BCG intravesical therapy is the first-line treatment for NMIBC, but about half of NMIBC patients relapse within two years after BCG treatment. Therefore, it is necessary to screen out lncRNAs related to the prognosis and tr ...[more]

PMID: 36011373

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Project description:BackgroundThe recently identified carcinogenic long non-coding RNA (lncRNA) MIR4435-2HG has been validated to contribute to the initiation and progression of several malignancies. Nonetheless, its specific mechanistic function in pancreatic cancer (PC) is yet to be determined. This study aims to investigate the expression and functional role of MIR4435-2HG in PC and to elucidate its potential mechanism.MethodsThis study employed The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx)-Pancreas datasets for the analysis of MIR4435-2HG expression in PC and normal pancreatic tissues and its relations with prognosis in PC. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was employed for analyzing MIR4435-2HG, miR-128-3p, and ABHD17C expressions within cells and tissues. Cell proliferation and apoptosis were detected in vitro through Cell Counting Kit 8 (CCK-8) assay and flow cytometry while utilizing transwell and wound healing assays to assess cell migration and invasion. Predicting miR-128-3p binding sites with MIR4435-2HG or ABHD17C was conducted via the online tool starBase and validated through a dual-luciferase reporter (DLR), RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Herein, we deployed Western blot to assess protein expression levels. The in vivo role of MIR4435-2HG was studied using tumor xenografts.ResultsMIR4435-2HG overexpression exhibited a correlation with poor prognosis in PC. Knocking down MIR4435-2HG significantly hindered the proliferative, invading, and migrating PC cell abilities, accompanied by apoptosis induction, counteracted via a miR-128-3p inhibitor. Moreover, MIR4435-2HG could directly bind to miR-128-3p. Additionally, miR-128-3p directly targeted ABHD17C. Furthermore, in vitro as well as in vivo experiment results elucidated that knocking down MIR4435-2HG hindered PC progression by suppressing ABHD17C expression via miR-128-3p upregulation.ConclusionsMIR4435-2HG can serve as a dependable target for PC diagnosis and treatment by modulating the miR-128-3p/ABHD17C axis to promote its progression.

Project description:Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. LncRNA-AL139385.1 (ENSG00000275880) is a novel lncRNA that is abnormally expressed in various cancer types including LUAD. However, the underlying biological function and potential mechanisms of AL139385.1 driving the progression of LUAD remain unclear. In this study, we investigated the role of AL139385.1 in LUAD and found that DNA hypomethylation was positively correlated with AL139385.1 expression in LUAD. Moreover, we uncover that the expression of AL139385.1 in LUAD tissues was significantly higher than that of AL139385.1 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher AL139385.1 expression correlated with adverse overall survival and progression-free survival. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of AL139385.1 was 0.808. Correlation analysis showed that AL139385.1 expression was associated with immune infiltration in LUAD. We also found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of AL139385.1 significantly inhibited cell proliferation and migration abilities of LUAD. Finally, we constructed a ceRNA network that includes hsa-miR-532-5p and four mRNAs (GALNT3, CYCS, EIF5A, and ITGB4) specific to AL139385.1 in LUAD. Subsequent Kaplan-Meier survival analysis suggested that polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), cytochrome c, somatic (CYCS), eukaryotic translation initiation factor 5A (EIF5A), and integrin subunit beta 4 (ITGB4), were potential prognostic biomarkers for patients with LUAD. In conclusion, this finding provides possible mechanisms underlying the abnormal upregulation of AL139385.1 as well as a comprehensive view of the AL139385.1-mediated competing endogenous RNAs (ceRNA) network in LUAD, thereby highlighting its potential role in diagnosis and therapy.

Project description:BackgroundH19, a 2.3 kb lncRNA, has been linked to tumor metastasis and progression, but its significance in oral squamous cell carcinoma (OSCC) remains unclear. H19 was initially thought to have a tumor-suppressive function, but recent studies have shown that it possesses both tumor-promoting and suppressive functions. The variation in H19 expression may be due to the influence of tobacco or low basal expression levels. However, there are limited studies available on the association between H19 and its role in the prognosis of OSCC.ObjectiveThe present study analyzes the expression of H19 correlated with clinicopathological parameters, tobacco habit, loco-regional recurrence, and overall survival.MethodsA longitudinal study was undertaken using 96 formalin-fixed paraffin-embedded (FFPE) OSCC tissues and 30 FFPE adjacent normal mucosa (NM) tissues from patients who had surgery between 2015 and 2018. The tissues were subjected to quantitative reverse-transcription PCR (qRT-PCR) to determine H19 expression. The differential expression levels of H19 in OSCC were compared to clinicopathological variables and risk habits using the t-test and ANOVA. H19 expression correlated overall survival was analyzed by drawing the Kaplan-Meier curve followed by the log-rank test. A multivariate Cox proportional hazards regression analysis was performed to determine the ability of H19 to independently predict loco-regional recurrence and overall survival for OSCC.ResultH19 was significantly underexpressed in OSCC compared to NM in both the study cases and the TCGA OSCC database. The lower expression of H19 was significantly associated with the tobacco smoking habit and was not associated with any clinical or pathological features. Multivariate Cox's proportional hazards regression analysis indicated that low H19 expression and positive lymph node metastasis were independent predictors of overall survival for OSCC. Higher age, higher TNM staging, and low H19 expression were independent predictors of loco-regional recurrence.ConclusionThe findings in the present study indicate that H19 is a novel prognostic marker and may provide a therapeutic strategy for the targeted treatment of OSCC, and tobacco may play a role in the expression of H19.

Project description:ObjectiveTo construct the prognostic model and identify the prognostic biomarkers based on long non-coding RNA (lncRNA) in bladder cancer.MethodsThe lncRNA expression data and corresponding clinical data of bladder cancer were collected from The Cancer Genome Atlas (TCGA) database. The software Perl and R, and R packages were used for data integration, extraction, analysis and visualization. Detailly, R package "edgeR" was utilized to screen differentially expressed lncRNA in bladder cancer tissues compared with the normal bladder samples. The univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) regression were performed to identify key lncRNA that were utilized to construct the prognostic model by the multivariate Cox regression. According to the median value of the risk score, all patients were divided into the high-risk group and low-risk group to perform the Kaplan-Meier (K-M) survival curves, receiver operating characteristic (ROC) curve and C-index, estimating the prognostic power of the prognostic model. In addition, the hazard ratio (HR) and 95% confidence interval (CI) of each key lncRNA were also calculated by the multivariate Cox regression. Moreover, we performed the K-M survival analysis for each significant key lncRNA from the result of the multivariate Cox regression.ResultsA total of 691 lncRNA were identified as differentially expressed lncRNA, and 35 lncRNA signatures were initially considered associated with the prognosis of bladder cancer, where in 23 lncRNA were identified as key lncRNA associated with the prognosis. The overall survival time in years of the low-risk group was obviously longer than that of the high-risk group [(2.85±2.72) years vs. (1.58±1.51) years, P<0.001]. The area under the ROC curve (AUC) was 0.813 (3-year survival) and 0.778 (5-year survival) respectively, and the C-index was 0.73. In addition, HR and 95%CI of each key lncRNA were calculated by the multivariate Cox regression and 11 lncRNA were significant. Furthermore, K-M survival analysis revealed the independent prognostic value of 3 lncRNA, including AL589765.1 (P=0.004), AC023824.1 (P=0.022)and PKN2-AS1 (P=0.016).ConclusionThe present study successfully constructed the prognostic model based on the expression level of 23 lncRNA and finally identified one protective prognostic biomarker AL589765.1, and two adverse prognostic biomarkers including AC023824.1 and PKN2-AS1 in bladder cancer.

Dataset Information

Identification of Long Non-Coding RNA MIR4435-2HG as a Prognostic Biomarker in Bladder Cancer.

Publications

Identification of Long Non-Coding RNA MIR4435-2HG as a Prognostic Biomarker in Bladder Cancer.

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