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Research Paper|Volume 12, Issue 14|pp 14174—14188

LncRNA NEAT1/miR-129/Bcl-2 signaling axis contributes to HDAC inhibitor tolerance in nasopharyngeal cancer

Fei Xue1, You Cheng1, Li Xu1, Chuan Tian2, Hongye Jiao1, Rui Wang2, Xia Gao3
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu, China
  • 2Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu, China
  • 3Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
* Equal contribution and Co-first authors
Received: December 13, 2019Accepted: May 25, 2020Published: July 21, 2020
https://doi.org/10.18632/aging.103427

Copyright: © 2020 Xue 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.

Abstract

Histone deacetylase inhibitors (HDACis) - based therapeutic drug tolerance is one of the principal factors of poor prognosis of patients with nasopharyngeal cancer (NPC). Mechanisms of tolerance to HDACis are not well understood. Nowadays, dysregulation of long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) has been reported to provide beneficial or inhibitory effects in drug-tolerance in various cancers. Herein, we established the HDAC inhibitor (SAHA)-tolerant NPC cell sublines, which had decreased apoptosis in response to SAHA treatment. We observed that the expression of miR-129 was significantly reduced in SAHA-tolerant NPC cells. Manipulating the expression of miR-129 overcame SAHA tolerance, and enhanced the SAHA-induced apoptosis. In terms of miR-129 downregulation, we identified that NEAT1 suppresses miR-129 expression. NEAT1 was found to be upregulated in SAHA tolerance cells. The depletion of NEAT1 phenocopied the effect of miR-129 overexpression, which also enhanced SAHA-induced apoptosis. Bcl-2 was the downstream target of miR-129 and contributed to SAHA tolerance in NPC. Our in vivo xenograft experiment confirmed that the administration of miR-129 or inhibition of Bcl-2 overcame the SAHA tolerance in NPC. In conclusion, NEAT1 increases in NPC tissues and manages to facilitate SAHA tolerance by modulating the miR-129/Bcl-2 axis, providing novel therapeutic targets for NPC treatment.