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Research Paper|Volume 11, Issue 24|pp 12624—12640

Long noncoding RNA NNT-AS1 enhances the malignant phenotype of bladder cancer by acting as a competing endogenous RNA on microRNA-496 thereby increasing HMGB1 expression

Deyao Wu1, Tielong Zhang2, Jie Wang1, Jian Zhou1, Huixing Pan1, Ping Qu1
  • 1Department of Urology, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng People’s Hospital, Yancheng 224001, China
  • 2Department of Urology, Jianhu Hospital Affiliated to Nantong University, Yancheng 224700, China
* Equal contribution
Received: September 20, 2019Accepted: November 26, 2019Published: December 17, 2019
https://doi.org/10.18632/aging.102591

Copyright © 2019 Wu 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

The long noncoding RNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a key malignancy regulator in a variety of human cancers. In this study, we first measured the expression of NNT-AS1 in bladder cancer and examined its role in cancer progression. The mechanisms behind the oncogenic functions of NNT-AS1 in bladder cancer were explored. We found that NNT-AS1 was upregulated in bladder cancer tissues and cell lines. This increased expression demonstrated a significant correlation with advanced clinical stage, lymph node metastasis, and shorter overall survival. NNT-AS1 knockdown suppressed bladder cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro and hindered tumor growth in vivo. NNT-AS1 functioned as a competing endogenous RNA for microRNA-496 (miR-496), and the suppressive effects of NNT-AS1 knockdown on malignant characteristics were abrogated by miR-496 silencing. HMGB1 was identified as a direct target gene of miR-496 in bladder cancer, and HMGB1 expression was enhanced by NNT-AS1 via sponging of miR-496. In conclusion, the NNT-AS1–miR-496–HMGB1 pathway plays a significant role in the aggressive behavior of bladder cancer and may lead to new NNT-AS1–based diagnostics and therapeutics.