MicroRNA‑25 protects nucleus pulposus cells against apoptosis via targeting SUMO2 in intervertebral disc degeneration Retraction in /10.3892/mmr.2024.13212

Lei,Changbin; Li,Jian; Tang,Guang; Wang,Jiong

doi:10.3892/mmr.2021.12363

MicroRNA‑25 protects nucleus pulposus cells against apoptosis via targeting SUMO2 in intervertebral disc degeneration

Retraction in: /10.3892/mmr.2024.13212

Authors:
- Changbin Lei
- Jian Li
- Guang Tang
- Jiong Wang
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Affiliations: Department of Clinical Medical Research Center, Affiliated Hospital of Xiangnan University (Clinical College), Chenzhou, Hunan 423000, P.R. China, Department of Heavy Metal Pollution and Cancer Prevention Technology Research Center, Affiliated Hospital of Xiangnan University (Clinical College), Chenzhou, Hunan 423000, P.R. China
Published online on: August 11, 2021 https://doi.org/10.3892/mmr.2021.12363
Article Number: 724

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Abstract

It has been reported that microRNA (miRNA/miR)‑25 is downregulated in patients with intervertebral disc degeneration (IVDD). However, the potential role of miR‑25 in IVDD remains unclear. Therefore, the present study aimed to investigate the effects of miR‑25 on human intervertebral disc nucleus pulposus cells (NPCs). The expression levels of miR‑25 and those of small ubiquitin‑related modifier 2 (SUMO2) were determined in human nucleus pulposus (NP) tissues by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analyses. Subsequently, the potential interaction between miR‑25 and SUMO2 was validated via dual‑luciferase reporter assay and RNA pull‑down assay with biotinylated miRNA. The effects of miR‑25 on NPC proliferation and apoptosis were evaluated using Cell Counting Kit‑8 assay, 5‑ethynyl‑2'‑deoxyuridine incorporation assay, and flow cytometry. The results showed that miR‑25 was downregulated in patients with IVDD. In addition, miR‑25 increased the proliferation of NPCs and inhibited their apoptosis. Furthermore, the current study verified that miR‑25 could directly target SUMO2 and regulate its expression via the p53 signaling pathway. Additionally, the effects of miR‑25 on NPCs were abrogated following SUMO2 overexpression. Overall, the results of the present study demonstrated that miR‑25 could promote the proliferation and inhibit the apoptosis of NPCs via targeting SUMO2, suggesting that miR‑25 may be a potential target in the treatment of IVDD.

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1	Vergroesen PP, Kingma I, Emanuel KS, Hoogendoorn RJ, Welting TJ, van Royen BJ, van Dieën JH and Smit TH: Mechanics and biology in intervertebral disc degeneration: A vicious circle. Osteoarthritis Cartilage. 23:1057–1070. 2015. View Article : Google Scholar : PubMed/NCBI
2	Sampara P, Banala RR, Vemuri SK, Av GR and Gpv S: Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: A review. Gene Ther. 25:67–82. 2018. View Article : Google Scholar : PubMed/NCBI
3	Cui S and Zhang L: circ_001653 silencing promotes the proliferation and ECM synthesis of NPCs in IDD by downregulating miR-486-3p-mediated CEMIP. Mol Ther Nucleic Acids. 20:385–399. 2020. View Article : Google Scholar : PubMed/NCBI
4	Zhan S, Wang K, Xiang Q, Song Y, Li S, Liang H, Luo R, Wang B, Liao Z, Zhang Y and Yang C: lncRNA HOTAIR upregulates autophagy to promote apoptosis and senescence of nucleus pulposus cells. J Cell Physiol. 235:2195–2208. 2020. View Article : Google Scholar : PubMed/NCBI
5	Sheppard JJ, Malandraki GA, Pifer P, Cuff J, Troche M, Hemsley B, Balandin S, Mishra A and Hochman R: Validation of the choking risk assessment and pneumonia risk assessment for adults with intellectual and developmental disability (IDD). Res Dev Disabil. 69:61–76. 2017. View Article : Google Scholar : PubMed/NCBI
6	Li Z, Li X, Chen C, Li S, Shen J, Tse G, Chan MTV and Wu WKK: Long non-coding RNAs in nucleus pulposus cell function and intervertebral disc degeneration. Cell Prolif. 51:e124832018. View Article : Google Scholar : PubMed/NCBI
7	Zhu J, Zhang X, Gao W, Hu H, Wang X and Hao D: lncRNA/circRNA-miRNA-mRNA ceRNA network in lumbar intervertebral disc degeneration. Mol Med Rep. 20:3160–3174. 2019.PubMed/NCBI
8	Kim DY and Sung JH: Regulatory role of microRNAs in the proliferation and differentiation of adipose-derived stem cells. Histol Histopathol. 32:1–10. 2017.PubMed/NCBI
9	Zhou X, Chen L, Grad S, Alini M, Pan H, Yang D, Zhen W, Li Z, Huang S and Peng S: The roles and perspectives of microRNAs as biomarkers for intervertebral disc degeneration. J Tissue Eng Regen Med. 11:3481–3487. 2017. View Article : Google Scholar : PubMed/NCBI
10	Zhang CY, Chen CY, Wen HX, Song ZF and Hu PP: miR-182-5p enhances cisplatin resistance in epithelial ovarian cancer by downregulating GRB2. Eur J Gynaecol Oncol. 42:353–359. 2021. View Article : Google Scholar
11	Yang B, Li S, Zhu J, Huang S, Zhang A, Jia Z, Ding G and Zhang Y: miR-214 protects against uric acid-induced endothelial cell apoptosis. Front Med (Lausanne). 7:4112020. View Article : Google Scholar : PubMed/NCBI
12	Wu L, Cheng S, Meng Y and Huang Y: miR-194 regulates cisplatin resistance in colorectal cancer cells through targeting yes-associated protein. J Biomater Tissue Eng. 10:157–162. 2020. View Article : Google Scholar
13	Zhou J and Zhan Y: microRNA-221 (Mir-221) influences ovarian cancer cell proliferation and apoptosis through regulating suppressors of cytokine signaling 3-janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. J Biomater Tissue Eng. 10:889–894. 2020. View Article : Google Scholar
14	Chen H, Pan H, Qian Y, Zhou W and Liu X: MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Mol Cancer. 17:42018. View Article : Google Scholar : PubMed/NCBI
15	Wan W, Wan W, Long Y, Li Q, Jin X, Wan G, Zhang F, Lv Y, Zheng G, Li Z and Zhu Y: MiR-25-3p promotes malignant phenotypes of retinoblastoma by regulating PTEN/Akt pathway. Biomed Pharmacother. 118:1091112019. View Article : Google Scholar : PubMed/NCBI
16	Liu B and Sun X: miR-25 promotes invasion of human non-small cell lung cancer via CDH1. Bioengineered. 10:271–281. 2019. View Article : Google Scholar : PubMed/NCBI
17	Zhao B, Yu Q, Li H, Guo X and He X: Characterization of microRNA expression profiles in patients with intervertebral disc degeneration. Int J Mol Med. 33:43–50. 2014. View Article : Google Scholar : PubMed/NCBI
18	Liang Q, Deng H, Li X, Wu X, Tang Q, Chang TH, Peng H, Rauscher FJ III, Ozato K and Zhu F: Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7. J Immunol. 187:4754–4763. 2011. View Article : Google Scholar : PubMed/NCBI
19	Agbor TA, Cheong A, Comerford KM, Scholz CC, Bruning U, Clarke A, Cummins EP, Cagney G and Taylor CT: Small ubiquitin-related modifier (SUMO)-1 promotes glycolysis in hypoxia. J Biol Chem. 286:4718–4726. 2011. View Article : Google Scholar : PubMed/NCBI
20	Kim YR, Jacobs JS, Li Q, Gaddam RR, Vikram A, Liu J, Kassan M, Irani K and Kumar S: SUMO2 regulates vascular endothelial function and oxidative stress in mice. Am J Physiol Heart Circ Physiol. 317:H1292–H1300. 2019. View Article : Google Scholar : PubMed/NCBI
21	Oh CH, Kim DY, Ji GY, Kim YJ, Yoon SH, Hyun D, Kim EY, Park H and Park HC: Cervical arthroplasty for moderate to severe disc degeneration: Clinical and radiological assessments after a minimum follow-Up of 18 months-pfirrmann grade and cervical arthroplasty 55. Yonsei Med J. 55:1072–1079. 2014. View Article : Google Scholar : PubMed/NCBI
22	Zhang B, Guo W, Sun C, Duan HQ, Yu BB, Mu K, Guan YY, Li Y, Liu S, Liu Y, et al: Dysregulated MiR-3150a-3p promotes lumbar intervertebral disc degeneration by targeting aggrecan. Cell Physiol Biochem. 45:2506–2515. 2018. View Article : Google Scholar : PubMed/NCBI
23	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. View Article : Google Scholar : PubMed/NCBI
24	Sherafatian M, Abdollahpour HR, Ghaffarpasand F, Yaghmaei S, Azadegan M and Heidari M: MicroRNA expression profiles, target genes, and pathways in intervertebral disk degeneration: A meta-analysis of 3 microarray studies. World Neurosurg. 126:389–397. 2019. View Article : Google Scholar : PubMed/NCBI
25	Hu P, Feng B, Wang G, Ning B and Jia T: Microarray based analysis of gene regulation by microRNA in intervertebral disc degeneration. Mol Med Rep. 12:4925–4930. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zhang Z, Huo Y, Zhou Z, Zhang P and Hu J: Role of lncRNA PART1 in intervertebral disc degeneration and associated underlying mechanism. Exp Ther Med. 21:1312021. View Article : Google Scholar : PubMed/NCBI
27	Cheng X, Zhang G, Zhang L, Hu Y, Zhang K, Sun X, Zhao C, Li H, Li YM and Zhao J: Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration. J Cell Mol Med. 22:261–276. 2018. View Article : Google Scholar : PubMed/NCBI
28	Sun Z, Jian Y, Fu H and Li B: MiR-532 downregulation of the Wnt/β-catenin signaling via targeting Bcl-9 and induced human intervertebral disc nucleus pulposus cells apoptosis. J Pharmacol Sci. 138:263–270. 2018. View Article : Google Scholar : PubMed/NCBI
29	Zhang Y, Yang J, Zhou X, Wang N, Li Z, Zhou Y, Feng J, Shen D and Zhao W: Knockdown of miR-222 inhibits inflammation and the apoptosis of LPS-stimulated human intervertebral disc nucleus pulposus cells. Int J Mol Med. 44:1357–1365. 2019.PubMed/NCBI
30	Tafrihi M and Hasheminasab E: MiRNAs: Biology, biogenesis, their web-based tools, and databases. Microrna. 8:4–27. 2019. View Article : Google Scholar : PubMed/NCBI
31	Liu B, Li J and Cairns MJ: Identifying miRNAs, targets and functions. Brief Bioinform. 15:1–19. 2014. View Article : Google Scholar : PubMed/NCBI
32	Zhao X: SUMO-mediated regulation of nuclear functions and signaling processes. Mol Cell. 71:409–418. 2018. View Article : Google Scholar : PubMed/NCBI
33	Mahmud I and Liao D: DAXX in cancer: Phenomena, processes, mechanisms and regulation. Nucleic Acids Res. 47:7734–7752. 2019. View Article : Google Scholar : PubMed/NCBI
34	Choi SG, Kim H, Jeong EI, Lee HJ, Park S, Lee SY, Lee HJ, Lee SW, Chung CH and Jung YK: SUMO-modified FADD recruits cytosolic Drp1 and caspase-10 to mitochondria for regulated necrosis. Mol Cell Biol. 37:e00254–16. 2017. View Article : Google Scholar
35	Ashikari D, Takayama K, Tanaka T, Suzuki Y, Obinata D, Fujimura T, Urano T, Takahashi S and Inoue S: Androgen induces G3BP2 and SUMO-mediated p53 nuclear export in prostate cancer. Oncogene. 36:6272–6281. 2017. View Article : Google Scholar : PubMed/NCBI
36	Wang F, Cai F, Shi R, Wei JN and Wu XT: Hypoxia regulates sumoylation pathways in intervertebral disc cells: Implications for hypoxic adaptations. Osteoarthritis Cartilage. 24:1113–1124. 2016. View Article : Google Scholar : PubMed/NCBI
37	Jin LZ, Lu JS and Gao JW: Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration. Biosci Rep. 38:BSR201715232018. View Article : Google Scholar : PubMed/NCBI
38	Yu S, Galeffi F, Rodriguiz RM, Wang Z, Shen Y, Lyu J, Li R, Bernstock JD, Johnson KR, Liu S, et al: Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice. FASEB J. 34:14750–14767. 2020. View Article : Google Scholar : PubMed/NCBI