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MicroRNA-488-3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma
Authors:Yi Yang  He Li  Zhifeng He  Deyao Xie  Jiangwei Ni  Xiaoming Lin
Institution:1. Department of Clinical Skills Center, Wenzhou Medical University, Wenzhou, Zhejiang, China;2. Department of Otolaryngoloy-Head and Neck Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China;3. Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
Abstract:Esophageal squamous cell carcinoma (ESCC) is the eighth most prevalent cancer and the sixth leading cause for cancer-associated mortality. MicroRNAs (miRNAs) are increasingly reported to exert important regulatory functions in human cancers by regulating certain gene expression. miR-488-3p has been identified to be a tumor suppressor in multiple cancers, but its role in ESCC is yet to be investigated. The present study aimed to uncover the biological role and modulatory mechanism of miR-488-3p in ESCC. We first revealed the downregulation of miR-488-3p in ESCC tissues and cell lines. Gain-of-function assays confirmed that miR-488-3p overexpression abrogated proliferation and accelerated apoptosis. Mechanistically, we identified via bioinformatics tool and confirmed that zinc finger and BTB domain containing 2 (ZBTB2) was a target for miR-488-3p. Moreover, miR-488-3p activated the p53 pathway through suppressing ZBTB2. Finally, rescue assays proved that ZBTB2 was involved in the regulation of miR-488-3p on proliferation and apoptosis in ESCC. Additionally, we verified that miR-488-3p had alternate targets in ESCC by confirming the involvement of protein kinase, DNA-activated, catalytic subunit (PRKDC), a known target for miR-488-3p, in miR-488-3p-mediated regulation on ESCC. In sum, this study revealed that miR-488-3p inhibited proliferation and induced apoptosis by targeting ZBTB2 and activating p53 pathway in esophageal squamous cell carcinoma, providing a novel biological target for ESCC.
Keywords:esophageal squamous cell carcinoma  miR-488-3p  tumor progression  zinc finger and BTB domain containing 2
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