Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis

Zhan,Daolu; Lin,Mingxia; Chen,Jian; Cai,Wentao; Liu,Jian; Fang,Yehan; Li,Yibo; Wu,Bin; Wang,Guangji

doi:10.3892/etm.2021.10078

Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis

Authors:
- Daolu Zhan
- Mingxia Lin
- Jian Chen
- Wentao Cai
- Jian Liu
- Yehan Fang
- Yibo Li
- Bin Wu
- Guangji Wang
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Affiliations: Department of Spine Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Xiuying, Haikou, Hainan 570311, P.R. China, Department of Sports Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Xiuying, Haikou, Hainan 570311, P.R. China
Published online on: April 18, 2021 https://doi.org/10.3892/etm.2021.10078
Article Number: 646
Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intervertebral disc degeneration and resulting low back pain arises from the programmed apoptosis of nucleus pulposus cells (NPCs). Recent studies show that hypoxia‑inducible factor‑1α plays a vital role in the etiology and pathogenesis of disc degeneration. However, the underlying mechanism of HIF‑1α in NPCs is unclear. The present study identified 994 significant differentially expressed miRNAs by analyzing microarray data downloaded from the Gene Expression Omnibus database. MicroRNA(miR)‑32‑5p expression was 2.81‑fold upregulated in NPCs compared with that of the healthy control tissues (P<0.05). A total of 331 significant differentially expressed mRNAs were identified, and PTEN was downregulated in NPCs of non‑degenerative disc tissues from young patients. miR‑32‑5p was predicted to target the PTEN 3'‑untranslated region (UTR). To confirm these results, in‑vitro experiments investigating the molecular function of miR‑32‑5p and PTEN were performed. Furthermore, hypoxia induced miR‑32‑5p and PTEN expression. HIF‑1α inhibited NPC proliferation and promoted cell apoptosis by regulating miR‑32‑5p and PTEN. miR‑32‑5p promoted NPC proliferation and decreased cell apoptosis. Next, it was verified whether miR‑32‑5p targeted the PTEN 3'‑UTR using dual‑luciferase reporter assays. Finally, it was observed that PI3K/AKT/mTOR signaling pathway was upregulated by a miR‑32‑5p mimic, which improved cell proliferation and decreased apoptosis. Importantly, PTEN was downregulated in these experiments; and inhibition of miR‑32‑5p had the opposite effect. Overall, these results demonstrate that HIF‑1α regulates cell proliferation and apoptosis by controlling the miR‑32‑5p/PTEN/PI3K/AKT/mTOR axis in NPCs.

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