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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
  • View Affiliations / Copyright

    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
    Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 646
    |
    Published online on: April 18, 2021
       https://doi.org/10.3892/etm.2021.10078
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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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1 

Ji ML, Jiang H, Zhang XJ, Shi PL, Li C, Wu H, Wu XT, Wang YT, Wang C and Lu J: Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Nat Commun. 9(5051)2018.PubMed/NCBI View Article : Google Scholar

2 

Sloan SR Jr, Wipplinger C, Kirnaz S, Navarro-Ramirez R, Schmidt F, McCloskey D, Pannellini T, Schiavinato A, Härtl R and Bonassar LJ: Combined nucleus pulposus augmentation and annulus fibrosus repair prevents acute intervertebral disc degeneration after discectomy. Sci Transl Med. 12(eaay2380)2020.PubMed/NCBI View Article : Google Scholar

3 

Madhu V, Boneski PK, Silagi E, Qiu Y, Kurland I, Guntur AR, Shapiro IM and Risbud MV: Hypoxic regulation of mitochondrial metabolism and mitophagy in nucleus pulposus cells is dependent on HIF-1α-BNIP3 Axis. J Bone Miner Res. 35:1504–1524. 2020.PubMed/NCBI View Article : Google Scholar

4 

Hamid AA, Gray KP, Shaw G, MacConaill LE, Evan C, Bernard B, Loda M, Corcoran NM, Van Allen EM, Choudhury AD and Sweeney CJ: Compound genomic alterations of TP53, PTEN, and RB1 tumor suppressors in localized and metastatic prostate cancer. Eur Urol. 76:89–97. 2019.PubMed/NCBI View Article : Google Scholar

5 

Meng J, Zhang W, Wang C, Zhang W, Zhou C, Jiang G, Hong J, Yan S and Yan W: Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity. Biochem Pharmacol. 171(113715)2020.PubMed/NCBI View Article : Google Scholar

6 

Liu H, Huang X, Liu X, Xiao S, Zhang Y, Xiang T, Shen X, Wang G and Sheng B: miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci. 15:4007–4018. 2014.PubMed/NCBI View Article : Google Scholar

7 

Lin Y, Guo W, Chen KW and Xiao ZM: VO-OHpic attenuates intervertebral disc degeneration via PTEN/Akt pathway. Eur Rev Med Pharmacol Sci. 24:2811–2819. 2020.PubMed/NCBI View Article : Google Scholar

8 

Wang M, Sun Y, Xu J, Lu J, Wang K, Yang DR, Yang G, Li G and Chang C: Preclinical studies using miR-32-5p to suppress clear cell renal cell carcinoma metastasis via altering the miR-32-5p/TR4/HGF/Met signaling. Int J Cancer. 143:100–112. 2018.PubMed/NCBI View Article : Google Scholar

9 

Zhao L, Han T, Li Y, Sun J, Zhang S, Liu Y, Shan B, Zheng D and Shi J: The lncRNA SNHG5/miR-32 axis regulates gastric cancer cell proliferation and migration by targeting KLF4. FASEB J. 31:893–903. 2017.PubMed/NCBI View Article : Google Scholar

10 

Wu W, Yang J, Feng X, Wang H, Ye S, Yang P, Tan W, Wei G and Zhou Y: MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells. Mol Cancer. 12(30)2013.PubMed/NCBI View Article : Google Scholar

11 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

12 

Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KS, et al: Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun. 3(1264)2012.PubMed/NCBI View Article : Google Scholar

13 

Smith LJ, Silverman L, Sakai D, Le Maitre CL, Mauck RL, Malhotra NR, Lotz JC and Buckley CT: Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section. JOR Spine. 1(e1036)2018.PubMed/NCBI View Article : Google Scholar

14 

Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, Xu C, McKenzie JA, Zhang C, Liang X, et al: Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 6:202–216. 2016.PubMed/NCBI View Article : Google Scholar

15 

Yang D, Ma M, Zhou W, Yang B and Xiao C: Inhibition of miR-32 activity promoted EMT induced by PM2.5 exposure through the modulation of the Smad1-mediated signaling pathways in lung cancer cells. Chemosphere. 184:289–298. 2017.PubMed/NCBI View Article : Google Scholar

16 

Li H, Jia Y and Wang Y: Targeting HIF-1α signaling pathway for gastric cancer treatment. Pharmazie. 74:3–7. 2019.PubMed/NCBI View Article : Google Scholar

17 

Ling S, Shan Q, Zhan Q, Ye Q, Liu P, Xu S, He X, Ma J, Xiang J, Jiang G, et al: USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation. Gut. 69:1322–1334. 2020.PubMed/NCBI View Article : Google Scholar

18 

Liu J, Zhang X, Chen K, Cheng Y, Liu S, Xia M, Chen Y, Zhu H, Li Z and Cao X: CCR7 Chemokine receptor-inducible inc-Dpf3 restrains dendritic cell migration by inhibiting HIF-1α-mediated glycolysis. Immunity. 50:600–615.e15. 2019.PubMed/NCBI View Article : Google Scholar

19 

Stegen S, Laperre K, Eelen G, Rinaldi G, Fraisl P, Torrekens S, Van Looveren R, Loopmans S, Bultynck G, Vinckier S, et al: HIF-1α metabolically controls collagen synthesis and modification in chondrocytes. Nature. 565:511–515. 2019.PubMed/NCBI View Article : Google Scholar

20 

Wu FQ, Fang T, Yu LX, Lv GS, Lv HW, Liang D, Li T, Wang CZ, Tan YX, Ding J, et al: ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α. J Hepatol. 65:314–324. 2016.PubMed/NCBI View Article : Google Scholar

21 

Chen J and Steidl U: Inhibition of HIF1α Signaling: A grand slam for MDS therapy? Cancer Discov. 8:1355–1357. 2018.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Zhan D, Lin M, Chen J, Cai W, Liu J, Fang Y, Li Y, Wu B and Wang G: Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis. Exp Ther Med 21: 646, 2021.
APA
Zhan, D., Lin, M., Chen, J., Cai, W., Liu, J., Fang, Y. ... Wang, G. (2021). Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis. Experimental and Therapeutic Medicine, 21, 646. https://doi.org/10.3892/etm.2021.10078
MLA
Zhan, D., Lin, M., Chen, J., Cai, W., Liu, J., Fang, Y., Li, Y., Wu, B., Wang, G."Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis". Experimental and Therapeutic Medicine 21.6 (2021): 646.
Chicago
Zhan, D., Lin, M., Chen, J., Cai, W., Liu, J., Fang, Y., Li, Y., Wu, B., Wang, G."Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis". Experimental and Therapeutic Medicine 21, no. 6 (2021): 646. https://doi.org/10.3892/etm.2021.10078
Copy and paste a formatted citation
x
Spandidos Publications style
Zhan D, Lin M, Chen J, Cai W, Liu J, Fang Y, Li Y, Wu B and Wang G: Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis. Exp Ther Med 21: 646, 2021.
APA
Zhan, D., Lin, M., Chen, J., Cai, W., Liu, J., Fang, Y. ... Wang, G. (2021). Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis. Experimental and Therapeutic Medicine, 21, 646. https://doi.org/10.3892/etm.2021.10078
MLA
Zhan, D., Lin, M., Chen, J., Cai, W., Liu, J., Fang, Y., Li, Y., Wu, B., Wang, G."Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis". Experimental and Therapeutic Medicine 21.6 (2021): 646.
Chicago
Zhan, D., Lin, M., Chen, J., Cai, W., Liu, J., Fang, Y., Li, Y., Wu, B., Wang, G."Hypoxia‑inducible factor‑1α regulates PI3K/AKT signaling through microRNA‑32‑5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis". Experimental and Therapeutic Medicine 21, no. 6 (2021): 646. https://doi.org/10.3892/etm.2021.10078
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