DNA methylation-mediated repression of exosomal miR-652-5p expression promotes oesophageal squamous cell carcinoma aggressiveness by targeting PARG and VEGF pathways

• Published in: PLoS genetics Vol. 16; no. 4; p. e1008592
• Main Authors: Gao, Peng, Wang, Dan, Liu, Meiyue, Chen, Siyuan, Yang, Zhao, Zhang, Jie, Wang, Huan, Niu, Yi, Wang, Wei, Yang, Jilong, Sun, Guogui
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-04-2020; Public Library of Science (PLoS)
• Subjects: Animals; Authorship; Biology and life sciences; Biomarkers; Cancer therapies; Cell cycle; Cell Movement; Cell proliferation; Cell Proliferation - genetics; CpG islands; Disease prevention; Disease Progression; DNA Methylation; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; Exosomes - genetics; Gene Expression Regulation, Neoplastic; Glycoside Hydrolases - metabolism; Humans; Laboratories; Lymph nodes; Lymphatic system; Medical prognosis; Medicine and Health Sciences; Metastases; Metastasis; Mice; MicroRNAs; MicroRNAs - genetics; miRNA; Neoplasm Metastasis - genetics; Oncology; Research and Analysis Methods; Ribose; Serum - cytology; Signal Transduction; Squamous cell carcinoma; Supervision; Survival Rate; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Visualization; China
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008592

Exosomal microRNAs (miRNAs) have been recently shown to play vital regulatory and communication roles in cancers. In this study, we showed that the expression levels of miR-652-5p in tumour tissues and serum samples of oesophageal squamous cell carcinoma (OSCC) patients were lower compared to non-tumorous tissues and serum samples from healthy subjects, respectively. Decreased expression of miR-652-5p was correlated with TNM stages, lymph node metastasis, and short overall survival (OS). More frequent CpG sites hypermethylation in the upstream of miR-652-5p was found in OSCC tissues compared to adjacent normal tissues. Subsequently, miR-652-5p downregulation promoted the proliferation and metastasis of OSCC, and regulated cell cycle both in cells and in vivo. The dual-luciferase reporter assay confirmed that poly (ADP-ribose) glycohydrolase (PARG) and vascular endothelial growth factor A (VEGFA) were the direct targets of miR-652-5p. Moreover, the delivery of miR-652-5p agomir suppressed tumour growth and metastasis, and inhibited the protein expressions of PARG and VEGFA in nude mice. Taken together, our findings provide novel insight into the molecular mechanism underlying OSCC pathogenesis.