Long non‑coding RNA HOXA‑AS2 promotes the expression levels of hypoxia‑inducible factor‑1&alpha; and programmed death‑ligand&nbsp;1, and regulates nasopharyngeal carcinoma progression via miR‑519

Wang,Shuyong; You,Huizeng; Yu,Sa

doi:10.3892/ol.2020.12107

November-2020 Volume 20 Issue 5

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November-2020 Volume 20 Issue 5

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Long non‑coding RNA HOXA‑AS2 promotes the expression levels of hypoxia‑inducible factor‑1α and programmed death‑ligand 1, and regulates nasopharyngeal carcinoma progression via miR‑519

Authors:
- Shuyong Wang
- Huizeng You
- Sa Yu
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Affiliations: Department of Otolaryngology, Weifang Traditional Chinese Medicine Hospital, Weifang, Shandong 261041, P.R. China, Department of Otorhinolaryngology, Head and Neck Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang 311800, P.R. China

Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 245
|
Published online on: September 15, 2020

https://doi.org/10.3892/ol.2020.12107
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Abstract

Nasopharyngeal carcinoma (NPC) is a rare malignancy arising from the nasopharyngeal epithelium and belongs to the group of head and neck cancer types, which are usually associated with viral and/or environmental influences, as well as heredity causes. A recent study reported that the long non‑coding RNA (lncRNA) HOXA cluster antisense RNA 2 (HOXA‑AS2) may be a prognostic biomarker in NPC; however, the specific mechanisms underlying NCP progression are yet to be determined. The aim of the present study was to investigate the biological role of HOXA‑AS2 in NPC. In the present study, the gene expression levels of HOXA‑AS2, miR‑519, hypoxia‑inducible factor (HIF‑1α) and programmed death‑ligand 1 (PD‑L1) were detected using reverse transcription‑quantitative PCR (RT‑qPCR) analysis and western blotting. Bioinformatics analysis and a dual luciferase reporter assay were performed to predict and confirm the direct interactions between HOXA‑AS2 and microRNA (miR)‑519, as well as between miR‑519 and HIF‑1α. A MTT assay was used to detect the cell viability, while cell migratory and invasive abilities were assessed using wound healing and Transwell assays. HOXA‑AS2 and HIF‑1α were found to be significantly upregulated in NPC tumor tissues, as well as in NPC cell lines. The overexpression of HOXA‑AS2 significantly enhanced NPC progression, including the cell proliferative, migratory and invasive abilities. HOXA‑AS2 was identified to directly bind to miR‑519, whereas a miR‑519 inhibitor significantly rescued the HOXA‑AS2 knockdown‑attenuated progression of NPC. Moreover, miR‑519 could bind to HIF‑1α and PD‑L1. Overexpression of HIF‑1α and PD‑L1 significantly promoted NPC progression and partially recovered the phenotype of NPC cells attenuated by HOXA‑AS2 knockdown. In conclusion, the present study demonstrated that HOXA‑AS2/miR‑519/HIF‑1α and/or HOXA‑AS2/miR‑519/PD‑L1 may be a novel mechanism regulating the progression of NPC, which may facilitate the development of targeted clinical therapy.

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