Exp Ther Med. 2021 Jun;21(6):646. doi: 10.3892/etm.2021.10078. Epub 2021 Apr 18.
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 confir m 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.
PMID:33968177 | PMC:PMC8097185 | DOI:10.3892/etm.2021.10078
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