Dataset Information

Diagnostic and prognostic value of circular RNA CDR1as/ciRS-7 for solid tumours: A systematic review and meta-analysis.

ABSTRACT: The circular RNA, CDR1as/ciRS-7, functions as a vital regulator in various cancers; however, the predictive value of CDR1as remains controversial. Therefore, a comprehensive analysis for clarifying the precise diagnostic and prognostic value of CDR1as in solid tumours is needed. A literature review of several databases was conducted for identifying potential studies. Pooled odds ratios (ORs) and hazard ratios (HRs) were used for evaluating the diagnostic accuracy variables and survival. Overall, 15 studies (1787 patients) and 11 studies (1578 patients) were included for diagnostic and prognostic outcome syntheses, respectively. Up-regulated CDR1as expression was found to be correlated with worse clinicopathological characteristics, including the T status, N status, histological grade, TNM stage and distant metastasis. The synthesized sensitivity was 0.72 (95% confidence interval [CI], 0.65-0.79), and the specificity was 0.80 (95% CI, 0.74-0.86). The positive likelihood ratio (LR), negative LR and diagnostic odds ratio (DOR) were 3.70, 0.34 and 10.80, respectively. The area under the receiver operator characteristic curve was 0.84 (95% CI, 0.80-0.87). In the pooled prognostic analysis, patients with high CDR1as expression had worse overall survival (HR = 2.40, P < 0.001) and disease-free survival (HR = 1.74, P < 0.001). These results suggest that CDR1as is a reliable diagnostic and prognostic biomarker with high accuracy and efficiency, which may potentially facilitate clinical decisions on solid tumours in the future.

SUBMITTER: Zou Y

PROVIDER: S-EPMC7520288 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Diagnostic and prognostic value of circular RNA CDR1as/ciRS-7 for solid tumours: A systematic review and meta-analysis.

Zou Yutian Y Zheng Shaoquan S Deng Xinpei X Yang Anli A Kong Yanan Y Kohansal Maryam M Hu Xiaoqian X Xie Xiaoming X

Journal of cellular and molecular medicine 20200812 17

The circular RNA, CDR1as/ciRS-7, functions as a vital regulator in various cancers; however, the predictive value of CDR1as remains controversial. Therefore, a comprehensive analysis for clarifying the precise diagnostic and prognostic value of CDR1as in solid tumours is needed. A literature review of several databases was conducted for identifying potential studies. Pooled odds ratios (ORs) and hazard ratios (HRs) were used for evaluating the diagnostic accuracy variables and survival. Overall, ...[more]

PMID: 32783378

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Project description:Background:Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis. As a member of circRNAs, ciRS-7 is thought to be a negative prognostic indicator in multiple types of cancer. The present study aimed to comprehensively explore the value of ciRS-7 in tumor malignancy. Materials and Methods. A systematic review of PubMed, Web of Science, and the Cochrane library was carried out to examine the related studies. The pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from the available publications by STATA 12.0. Subgroup analysis, publication bias, sensitivity analysis, and meta-regression were conducted. Results:This meta-analysis included 1,714 patients from 13 cohorts. The results suggested that high ciRS-7 expression was significantly associated with overall survival (OS) (HR?=?2.17, 95% CI?=?1.50-3.15, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07, P < 0.001) in various cancers. Stratified analyses indicated that elevated levels of ciRS-7 appeared to be a powerful prognostic biomarker for patients with non-small-cell lung cancer (NSCLC) (HR: 2.50, 95% CI: 1.07-6.07. Conclusions:High expression of ciRS-7 has a significant correlation with the high stage in various cancers, and ciRS-7 is intimately associated with an adverse OS in numerous cancers. Thus, ciRS-7 may act as a potential biomarker for the development of malignancies.

Project description:BACKGROUND:Inactivation of the tumor suppressor p53 is critical for pathogenesis of glioma, in particular glioblastoma multiforme (GBM). MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. Hitherto, it is unclear whether the stability of the p53/MDM2 complex is affected by lncRNAs, in particular circular RNAs that are usually abundant and conserved, and frequently implicated in different oncogenic processes. METHODS:RIP-seq and RIP-qPCR assays were performed to determine the most enriched lncRNAs (including circular RNAs) bound by p53, followed by bioinformatic assays to estimate the relevance of their expression with p53 signaling and gliomagenesis. Subsequently, the clinical significance of CDR1as was evaluated in the largest cohort of Chinese glioma patients from CGGA (n?=?325), and its expression in human glioma tissues was further evaluated by RNA FISH and RT-qPCR, respectively. Assays combining RNA FISH with protein immunofluorescence were performed to determine co-localization of CDR1as and p53, followed by CHIRP assays to confirm RNA-protein interaction. Immunoblot assays were carried out to evaluate protein expression, p53/MDM2 interaction and p53 ubiquitination in cells in which CDR1as expression was manipulated. After AGO2 or Dicer was knocked-down to inhibit miRNA biogenesis, effects of CDR1as on p53 expression, stability and activity were determined by immunoblot, RT-qPCR and luciferase reporter assays. Meanwhile, impacts of CDR1as on DNA damage were evaluated by flow cytometric assays and immunohistochemistry. Tumorigenicity assays were performed to determine the effects of CDR1as on colony formation, cell proliferation, the cell cycle and apoptosis (in vitro), and on tumor volume/weight and survival of nude mice xenografted with GBM cells (in vivo). RESULTS:CDR1as is found to bind to p53 protein. CDR1as expression decreases with increasing glioma grade and it is a reliable independent predictor of overall survival in glioma, particularly in GBM. Through a mechanism independent of acting as a miRNA sponge, CDR1as stabilizes p53 protein by preventing it from ubiquitination. CDR1as directly interacts with the p53 DBD domain that is essential for MDM2 binding, thus disrupting the p53/MDM2 complex formation. Induced upon DNA damage, CDR1as may preserve p53 function and protect cells from DNA damage. Significantly, CDR1as inhibits tumor growth in vitro and in vivo, but has little impact in cells where p53 is absent or mutated. CONCLUSIONS:Rather than acting as a miRNA sponge, CDR1as functions as a tumor suppressor through binding directly to p53 at its DBD region to restrict MDM2 interaction. Thus, CDR1as binding disrupts the p53/MDM2 complex to prevent p53 from ubiquitination and degradation. CDR1as may also sense DNA damage signals and form a protective complex with p53 to preserve p53 function. Therefore, CDR1as depletion may play a potent role in promoting tumorigenesis through down-regulating p53 expression in glioma. Our results broaden further our understanding of the roles and mechanism of action of circular RNAs in general and CDR1as in particular, and can potentially open up novel therapeutic avenues for effective glioma treatment.

Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

Dataset Information

Diagnostic and prognostic value of circular RNA CDR1as/ciRS-7 for solid tumours: A systematic review and meta-analysis.

Publications

Diagnostic and prognostic value of circular RNA CDR1as/ciRS-7 for solid tumours: A systematic review and meta-analysis.

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