Extracellular vesicles promote esophageal cancer progression by delivering lncZEB1-AS1 between cells

Y.-G. Zhang, M.-W. Zhou, L. Bai, R.-Y. Han, K. Lv, Z. Wang

Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China. wangzhe8809@163.com

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• Oncology

OBJECTIVE: To explore the expression of extracellular vesicle-derived lncZEB1-AS1 in esophageal cancer and its role in esophageal cancer progression.

PATIENTS AND METHODS: The extracellular vesicles (EVs) from esophageal cancer patients (n = 26) and normal subjects (n = 26) were isolated by differential centrifugation. The expression of lncZEB1-AS1 in EVs was detected by Real-time PCR (polymerase chain reaction). The clinical data of normal subjects and patients were analyzed. In addition, the concentration of EVs and lncZEB1-AS1 in blood samples from normal subjects and esophageal cancer patients were assessed. After co-culture of esophageal cancer cell line EC109 and EVs with or without lncZEB1-AS1 knockdown, cell proliferation was detected by CCK-8 assay. The possible target microRNAs of lncZEB1-AS1 in cytoplasm were predicted with miRcode, followed by correlation analysis of lncZEB1-AS1 and miR-214. Through literature review, lncZEB1-AS1 positively regulates ZEB1 expression, which was consistent with our result.

RESULTS: Quantitative Real-time PCR showed that the serum levels of EVs and the content of lncZEB1-AS1 in EVs from esophageal cancer patients were significantly higher than those in normal controls. LncZEB1-AS1 was overexpressed in esophageal cancer cells co-cultured with EVs of esophageal cancer patients. CCK-8 results indicated that EC109 cells co-cultured with EVs of esophageal cancer patients had stronger proliferative capacity. miRcode showed that miR-214 ranked the first of microRNAs that lncZEB1-AS1 might target, and miR-214 expression was significantly increased after lncZEB1-AS1 knockdown in EC109. After overexpressing lncZEB1-AS1 in EC109 or co-culturing EVs of esophageal cancer patients with EC109 cells, we found that lncZEB1-AS1 positively regulates ZEB1. In contrast, interfering with the expression of lncZEB1-AS1 in esophageal cancer cell lines can effectively reduce the expression of ZEB1.

CONCLUSIONS: EVs in the peripheral blood from esophageal cancer patients promote esophageal cancer progression by delivering lncZEB1-AS1 to esophageal cancer cells and targeting miR-214.

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