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Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer.

ABSTRACT: Aim:Traditional non-invasive diagnostic markers for gastric cancer (GC) exhibit insufficient sensitivity and specificity. Circulating exosomes are clinically useful non-invasive biomarkers for tumor diagnosis. In addition to their potential role in cancer biology, circulating long non-coding RNAs (lncRNAs) are a new class of promising cancer biomarkers. In the present study, we aimed to identify lncRNAs in circulating exosomes with potential as biomarkers for GC detection. Methods:We compared the expression of CEBPA-AS1 between GC cells and gastric epithelial cells. The biological function of exosomal CEBPA-AS1 was determined by cell phenotype experiments and rescue assays. We also compared the expression of CEBPA-AS1 in cancerous tissue from GC patients and corresponding adjacent normal tissues, as well as the expression of CEBPA-AS1 in plasma exosomes of GC patients and healthy controls. Diagnostic accuracy was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results:CEBPA-AS1 was highly expressed in both GC cells and in exosomes secreted by GC cells. In addition, CEBPA-AS1-containing exosomes secreted by GC cells could promote cell proliferation and inhibit apoptosis, thereby inducing the malignant behavior of GC cells. The level of CEBPA-AS1 was also significantly increased in tissues and plasma exosomes of GC patients. Stability tests showed that most plasma CEBPA-AS1 was encased in exosomes, thus avoiding degradation by RNases. We evaluated the diagnostic accuracy of exosome-derived CEBPA-AS1. The AUC value of CEBPA-AS1 in discriminating GC patients from healthy controls was 0.824, which was higher than the diagnostic accuracy of other traditional tumor biomarkers. Conclusion:CEBPA-AS1-containing exosomes secreted from GC cells could promote cell proliferation, inhibit apoptosis, and induce GC progression, indicating that exosomal CEBPA-AS1 is involved in cell-to-cell communication in GC carcinogenesis. Exosomal CEBPA-AS1 is a promising new biomarker for clinical diagnosis of GC.

SUBMITTER: Piao HY

PROVIDER: S-EPMC7034294 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer.

Piao Hai-Yan HY Guo Shuai S Wang Yue Y Zhang Jun J

OncoTargets and therapy 20200214

<h4>Aim</h4>Traditional non-invasive diagnostic markers for gastric cancer (GC) exhibit insufficient sensitivity and specificity. Circulating exosomes are clinically useful non-invasive biomarkers for tumor diagnosis. In addition to their potential role in cancer biology, circulating long non-coding RNAs (lncRNAs) are a new class of promising cancer biomarkers. In the present study, we aimed to identify lncRNAs in circulating exosomes with potential as biomarkers for GC detection.<h4>Methods</h4 ...[more]

PMID: 32110038

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Project description:Background: Safe and sensitive methods for glioblastoma diagnosis and disease monitoring are urgently needed. Exosomes are nano-sized extracellular vesicles that contain molecules characteristic of their cell-of-origin, including microRNA. Exosomes released by glioblastoma tumors cross the blood-brain-barrier ino the peripheral circulation. Methods: Serum exosomal-microRNA isolated from IDH-wildtype glioblastoma (n=12) and IDH-mutant glioma grades II-III (n=10) were analyzed using small-RNA next generation sequencing and compared to age- and gender-matched healthy controls. Differentially expressed miRNAs (|fold change|³2 and p-value ≤ 0.05 in three statistical tests, Fischer-exact, t-test, and Wilcoxon) were identified and the predictive power of individual and subsets of miRNAs were tested using univariate (logistic regression) and multivariate (Random Forest) analyses. Additional glioblastoma sera (n=4) and independent sets of healthy (n=9) and non-glioma (n=10) controls were used to further test the predictive power of our glioblastoma miRNA signature. Results: Twenty-six miRNAs were differentially expressed in glioblastoma relative to healthy controls. Seven miRNAs (miR-182-5p, miR-328-3p, miR-339-5p, miR-340-5p, miR-485-3p, miR-486-5p and miR-543) were the most stable for classifying glioblastoma, achieving a predictive power of 91.7%. Strikingly, the combined expressions of miR-182-5p, miR-328-3p miR-485-3p miR-486-5p distinguished glioblastoma patients from controls with perfect accuracy. This miRNA panel was able to correctly classify all specimens in validation cohorts (n=23). An analogous approach was used to identify 23 dysregulated miRNAs in IDH-mutant gliomas, including a distinct subset of stable miRNAs for classifying patients with lower-grade IDH-mutant gliomas. Conclusions: Our serum exosomal-miRNA signature can accurately diagnose glioblastoma preoperatively. These findings have significant scope to revolutionize glioblastoma tumor diagnosis and disease monitoring. IMPORTANCE OF STUDY: There is a real need for accurate biomarkers that can measure glioblastoma disease activity and treatment response in a safe and timely manner. This study demonstrates that exosome-associated microRNAs have exceptional utility as blood-based biomarkers in glioma patients. This work also shows the potential for exosomal microRNA profiles to be used for glioma subtyping, grading and determining mutational states. The development of specific, sensitive and non-invasive screening tests would have significant clinical benefit by reducing costs of treatment monitoring, improving accessibility and quality-of-life measures. Moreover, such tests have the potential to provide objectively measured surrogate endpoints to allow clinical trial protocols to be more dynamic and adaptive.

Dataset Information

Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer.

Publications

Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer.

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