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.102618
How to Cite
Copyright © 2020 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
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.