HOXA11‑AS induces cisplatin resistance by modulating the microRNA‑98/PBX3 axis in nasopharyngeal carcinoma

Li,Haineng; Huang,Jia; Yu,Sa; Li,Hangbo; Zhou,Yan; Wu,Qingwei

doi:10.3892/ol.2021.12754

HOXA11‑AS induces cisplatin resistance by modulating the microRNA‑98/PBX3 axis in nasopharyngeal carcinoma

Authors:
- Haineng Li
- Jia Huang
- Sa Yu
- Hangbo Li
- Yan Zhou
- Qingwei Wu
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Affiliations: Department of Otolaryngology, Zhuji People's Hospital Affiliated to Shaoxing University, Zhuji, Zhejiang 311800, P.R. China, Department of Neurology, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China, Department of Otolaryngology‑Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
Published online on: April 26, 2021 https://doi.org/10.3892/ol.2021.12754
Article Number: 493
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA homeobox A11‑antisense RNA (HOXA11‑AS) has been implicated in cisplatin (DDP) resistance in multiple types of cancer. The purpose of the present study was to investigate the role of HOXA11‑AS in DDP‑resistant nasopharyngeal carcinoma (NPC) cells. The expression levels of HOXA11‑AS were examined using reverse transcription‑quantitative PCR. Cell viability was measured using a Cell Counting Kit‑8 assay, and a TUNEL assay was utilized to assess cell apoptosis. The expression levels of apoptosis‑related factors (Bax and Bcl‑2) were detected by western blot analysis. The interaction between microRNA‑98 (miR‑98) and HOXA11‑AS or pre‑B‑cell leukemia homeobox 3 (PBX3) was demonstrated using bioinformatics analysis, dual‑luciferase reporter assays and RNA immunoprecipitation assays. HOXA11‑AS and PBX3 expressions levels were upregulated, whereas miR‑98 levels were downregulated in DDP‑resistant NPC tissues. Patients with NPC with high HOXA11‑AS expression had a low survival rate. Knockdown of HOXA11‑AS enhanced the DDP sensitivity of DDP‑resistant NPC (5‑8F/DDP and SUNE1/DDP) cells, which was demonstrated by the accelerated apoptosis. In addition, HOXA11‑AS inhibited the expression levels of miR‑98 through direct interaction. Furthermore, miR‑98 inhibition counteracted the inductive effect of HOXA11‑AS‑knockdown on the DDP sensitivity of NPC cells. PBX3 was a target of miR‑98 and was positively modulated by HOXA11‑AS. Overexpression of PBX3 reversed the suppressive effect of HOXA11‑AS silencing on the DDP resistance of NPC cells. The data demonstrated that HOXA11‑AS enhanced DDP resistance in NPC via the miR‑98/PBX3 axis, providing a potential therapeutic target for patients with DDP‑resistant NPC.

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