Research Paper Volume 12, Issue 1 pp 340—358
Downregulation of ABI2 expression by EBV-miR-BART13-3p induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells through upregulation of c-JUN/SLUG signaling
- 1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Received: September 4, 2019 Accepted: December 5, 2019 Published: January 6, 2020
https://doi.org/10.18632/aging.102618How to Cite
Abstract
Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells in vitro and causes tumor metastasis in vivo. Furthermore, we find that EBV-miR-BART13-3p directly targets ABI2, known as a tumor suppressor and a cell migration inhibitor, drives epithelial-mesenchymal transition (EMT) by activating c-JUN/SLUG signaling pathway. Silencing ABI2 shows similar effects to overexpression of EBV-miR-BART13-3p, whereas reconstitution of ABI2 resulted in a phenotypic reversion, highlighting the role of ABI2 in EBV-miR-BART13-3p-driven metastasis in NPC. Besides, expression levels of ABI2 in NPC tissue samples correlate with N stages of NPC patients. Taken together, these results suggest a novel mechanism by which ABI2 downregulation by EBV-miR-BART13-3p promotes EMT and metastasis of NPC via upregulating c-JUN/SLUG signaling pathway.
Abbreviations
EBV: Epstein-Barr virus; NPC: Nasopharyngeal carcinoma; ABI2: Abl interactor 2; EMT: Epithelial-mesenchymal transition; IMRT: Intensity-modulated radiotherapy; BARTs: BamH I-A rightward transcripts; miRNA: MicroRNA; siRNA: Small interfering RNA; qRT-PCR: Quantitative real-time polymerase chain reaction; BSA: Bovine serum albumin; IHC: Immunohistochemistry; H&E: Hematoxylin and eosin; SEM: standard error of the mean; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.