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

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.