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

• Main Authors: Piao H, Guo S, Wang Y, Zhang J
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-02-01
• Series: OncoTargets and Therapy
• Subjects: gastric cancer; exosome; lncrnas; cebpa-as1; diagnosis
• Online Access: https://www.dovepress.com/exosomal-long-non-coding-rna-cebpa-as1-inhibits-tumor-apoptosis-and-fu-peer-reviewed-article-OTT

Hai-yan Piao,1 Shuai Guo,2 Yue Wang,2 Jun Zhang2 1Medical Oncology Department of Gastrointestinal Cancer, Liaoning Province Cancer Hospital and Institute (Cancer Hospital of China Medical University), Shenyang City, Liaoning Province 110042, People’s Republic of China; 2Gastric Cancer Department, Liaoning Province Cancer Hospital and Institute (Cancer Hospital of China Medical University), Shenyang City, Liaoning Province 110042, People’s Republic of ChinaCorrespondence: Jun ZhangGastric Cancer Department, Liaoning Province Cancer Hospital and Institute (Cancer Hospital of China Medical University), No. 44 Xiaoheyan Road, Dadong District, Shenyang City, Liaoning Province 110042, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]: 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.Keywords: gastric cancer, exosome, lncRNAs, CEBPA-AS1, diagnosis