Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November-2025 Volume 56 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2025 Volume 56 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.xlsx
    • Supplementary_Data3.xlsx
    • Supplementary_Data4.xlsx
    • Supplementary_Data5.xlsx
    • Supplementary_Data6.xlsx
Article Open Access

miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration

  • Authors:
    • Qiuwei Li
    • Chenhao Zhao
    • Peilin Jin
    • Cailiang Shen
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics and Spine Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Institute of Health and medicine, Hefei Comprehensive National Science Center, Economic and Technological Development Zone, Hefei, Anhui 230022, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 193
    |
    Published online on: September 11, 2025
       https://doi.org/10.3892/ijmm.2025.5634
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Intervertebral disc degeneration (IVDD) is a major cause of chronic back pain, yet its molecular mechanisms remain poorly understood despite its high prevalence. In the present study, the significant role of microRNA (miR)‑27b‑3p in regulating 731 immune cell types was systematically uncovered utilizing Mendelian randomization (MR) and single‑cell RNA sequencing, with a particular focus on CD4+CD39+ regulatory T cells (Tregs); and its critical impact on immune‑mediated IVDD progression was highlighted. A total of 76 miRs were screened and, through MR analysis, a significant causal relationship between miR‑27b‑3p and IVDD was identified. Subsequent in vivo and in vitro experiments demonstrated that miR‑27b‑3p overexpression not only promoted apoptosis of nucleus pulposus cells but also accelerated IVDD by modulating the immune functions of CD4+CD39+ Tregs. Single‑cell RNA sequencing further revealed a marked upregulation of immune‑related genes in degenerated discs, particularly those involved in immune cell migration, inflammation and apoptotic regulation pathways. These findings suggest that miR‑27b‑3p plays a pivotal role in IVDD by influencing various immune cells, especially CD4+CD39+ Tregs, underscoring its potential as a therapeutic target with significant clinical implications. Further research into the mechanisms of miR‑27b‑3p could open new avenues for IVDD treatment strategies, offering promising possibilities for future clinical applications.
View Figures

Figure 1

MR analysis of the effect of
miR-27a-3P on IVDD. (A) A forest map of 5 MR analysis methods. (B)
MR analysis of miR-27a-3P and IVDD with the leave-one-out approach.
(C) Scatter plots of the genetic association between miR-27a-3P and
risk of IVDD. (D) Funnel plots of the instrumental variables for
each significant causal relationship between miR-27a-3P and IVDD.
MR, Mendelian randomization; miR, microRNA; IVDD, intervertebral
disc degeneration.

Figure 2

Correlation and association analysis
of immune cells and their relationship with IVDD. (A) Heatmap
showing the P-values of the association between different immune
cell types and various parameters. (B) Forest plot depicting the
correlation between immune cell types and key variables related to
IVDD using the IVW method. IVDD, intervertebral disc degeneration;
IVW, Inverse variance weighting.

Figure 3

MR analysis of the effect of
miR-27a-3p on CD4 of CD4+CD39+ Tregs. (A)
Forest map of five MR analysis methods. (B) MR analysis of the
causal relationship between miR-27a-3P and CD4 on
CD4+CD39+ Tregs with the leave-one-out
method. (C) Scatter plots showing genetic association between
miR-27a-3P and CD4 on CD4+CD39+ Treg cells.
(D) Funnel plots of the instrumental variables for each significant
causal relationship between miR-27a-3P and CD4 on
CD4+CD39+ Treg cells. MR, Mendelian
randomization; miR, microRNA; Tregs, regulatory T cells; SNPs,
single nucleotide polymorphisms.

Figure 4

MR analysis of the effect of
miR-27a-3p on CD4 on CD4+CD39+ Tregs. (A)
Forest map of five MR analysis methods. (B) MR analysis of
miR-27a-3P and CD4 on CD4+CD39+ Tregs with
the leave-one-out method. (C) Scatter plots showing the genetic
association between miR-27a-3P and CD4 on
CD39+CD4+ Tregs. (D) Funnel plots of the
instrumental variables for each significant causal relationship
between miR-27a-3P and CD4 on CD4+CD39+
Tregs. MR, Mendelian randomization; miR, microRNA; Tregs,
regulatory T cells; IVW, Inverse variance weighting; SNPs, single
nucleotide polymorphisms.

Figure 5

Apoptosis of NP cells is induced by
miR-27a-3p. (A) TUNEL analysis of cells in the NC, LPS, miR-27a-3p,
LPS + miR-27a-3p, miR-27a-3p, inhibition, and LPS + miR-27a-3p
inhibition groups. (B-E) Expression levels of apoptosis-related
proteins and IVDD-related proteins of cells in the NC, LPS,
miR-27a-3p, and LPS + miR-27a-3p groups. (F-I) Expression levels of
apoptosis-related proteins and IVDD-related proteins of cells in
the NC, LPS, miR-27a-3p inhibition and LPS + miR-27a-3p inhibition
groups. *P<0.05, **P<0.01,
***P<0.001 and ****P<0.0001. NP,
nucleus pulposus; miR, microRNA; NC, negative control; LPS,
lipopolysaccharide; IVDD, intervertebral disc degeneration; ns, not
significant.

Figure 6

miR-27a-3p promotes NP cell apoptosis
through CD4+CD39+ Tregs. (A) Flow cytometry
of apoptosis in CD4+CD39+ Tregs after
addition of miR-27b-3p. (B) two groups of
CD4+CD39+ Tregs' apoptosis rate of bar chart.
(C) Flow cytometry of apoptosis of NP cells after adding
miR-27b-3p, CD4+CD39+ Tregs and miR-27b-3p +
CD4+CD39+ Tregs. (D) Bar chart demonstrating
the apoptotic rate of NP cells. (E) Flow cytometry of blood
CD4+CD39+ Tregs from normal and IVDD rats.
(F) Flow cytometry of CD4+CD39+ Tregs in NP
tissues from normal rats and IVDD rats. **P<0.01 and
****P<0.0001. miRNA or miR, microRNA; NP, nucleus
pulposus; Tregs, regulatory T cells.

Figure 7

Intervertebral disc degeneration in
rats is promoted by miR-27a-3p. (A) H&E and saffron green
staining of each group. (B) MRI of the tail vertebral body of rats
after relevant treatment. (C) Degeneration grading of the tail
vertebral disc of rats. (D) Histological grading of degeneration of
the rat tail vertebral disc. (E) Degeneration grading of the tail
vertebral disc of rats. (F) Fluorescence staining of Aggrecan and
Col2A in intervertebral disc tissue across different groups. Red
indicates positive signals, while blue represents background. (G
and H) Immunofluorescence intensity of Aggrecan and COL2A was
quantified, showing significant changes in expression levels
between groups. *P<0.05 and **P<0.01
(n=3). miR, microRNA; MRI, magnetic resonance imaging; NC, negative
control; LPS, lipopolysaccharide.

Figure 8

UMAP and functional analysis of
CD4+CD39+ Tregs in normal and degenerated
intervertebral discs. (A and B) UMAP plots showing the distribution
of CD4+CD39+ Tregs in Normal_NP) and
Degenerate_NP intervertebral disc samples. The cells are clustered
according to their gene expression profiles, revealing distinct
populations in each condition. Normal_NP samples exhibit a more
compact and uniform distribution of Tregs, while Degenerate_NP
samples show a more dispersed distribution, suggesting a shift in
Treg cell composition during disc degeneration. (C and D) Feature
plots highlight the expression of CD4 and ENTPD1 (CD39), used to
identify Tregs. (E) Distribution of CD4+CD39+
Tregs across different conditions. (F) Results of Gene Ontology
enrichment analysis, showing significant involvement of these cells
in biological processes such as monocyte activation and zinc ion
response. (G) Pseudotime trajectory analysis demonstrating dynamic
state transitions of CD4+CD39+ Tregs. (H)
Pseudotime-associated gene expression trends of ACAN,
BAX, BCL2, and COL2A1, illustrating altered
regulation of extracellular matrix and apoptosis pathways during
degeneration. Tregs, regulatory T cells; NP, nucleus pulposus.

Figure 9

miR-27b-3p target gene analysis and
functional impact on CD4+CD39+ regulatory T
cells. (A) Predicted target genes of miR-27b-3p, including genes
such as PPARG, CYP1B1 and WEE1. (B) Differential expression of
these target genes in normal and degenerated intervertebral disc
samples, with notable changes in genes such as PPARG, WEE1 and
MMP13. (C) Gene Ontology functional enrichment analysis of
miR-27b-3p target genes, highlighting their involvement in immune
cell migration, immune response regulation and cholesterol
metabolism. (D) Volcano plot of the differentially expressed
miR-27b-3p target genes, revealing both upregulated and
downregulated genes in degenerated discs. miR, microRNA.
View References

1 

Saberi M, Zhang X and Mobasheri A: Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration. Geroscience. 43:517–537. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Wang F, Cai F, Shi R, Wang XH and Wu XT: Aging and age related stresses: A senescence mechanism of intervertebral disc degeneration. Osteoarthritis Cartilage. 24:398–408. 2016. View Article : Google Scholar

3 

Wang Y, Cheng H, Wang T, Zhang K, Zhang Y and Kang X: Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment. Cell Prolif. 56:e134482023. View Article : Google Scholar : PubMed/NCBI

4 

Xiang Q, Zhao Y and Li W: Identification and validation of ferroptosis-related gene signature in intervertebral disc degeneration. Front Endocrinol (Lausanne). 14:10897962023. View Article : Google Scholar : PubMed/NCBI

5 

Yi J, Zhou Q, Huang J, Niu S, Ji G and Zheng T: Lipid metabolism disorder promotes the development of intervertebral disc degeneration. Biomed Pharmacother. 166:1154012023. View Article : Google Scholar : PubMed/NCBI

6 

Koroth J, Buko EO, Abbott R, Johnson CP, Ogle BM, Stone LS, Ellingson AM and Bradley EW: Macrophages and intervertebral disc degeneration. Int J Mol Sci. 24:13672023. View Article : Google Scholar : PubMed/NCBI

7 

Samanta A, Lufkin T and Kraus P: Intervertebral disc degeneration: Current therapeutic options and challenges. Front Public Health. 11:11567492023. View Article : Google Scholar

8 

Silwal P, Nguyen-Thai AM, Mohammad HA, Wang Y, Robbins PD, Lee JY and Vo NV: Cellular senescence in intervertebral disc aging and degeneration: Molecular mechanisms and potential therapeutic opportunities. Biomolecules. 13:6862023. View Article : Google Scholar : PubMed/NCBI

9 

Wang HS, Lin S and Yu HM: Exosome-mediated repair of intervertebral disc degeneration: The potential role of miRNAs. Curr Stem Cell Res Ther. 19:798–808. 2024. View Article : Google Scholar

10 

Sharma Y, Saini AK, Kashyap S, Chandan G, Kaur N, Gupta VK, Thakur VK, Saini V and Saini RV: Host miRNA and immune cell interactions: Relevance in nano-therapeutics for human health. Immunol Res. 70:1–18. 2022. View Article : Google Scholar

11 

Schell SL and Rahman ZSM: miRNA-mediated control of B cell responses in immunity and SLE. Front Immunol. 12:6837102021. View Article : Google Scholar : PubMed/NCBI

12 

Bronevetsky Y and Ansel KM: Regulation of miRNA biogenesis and turnover in the immune system. Immunol Rev. 253:304–316. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Wythe SE, Nicolaidou V and Horwood NJ: Cells of the immune system orchestrate changes in bone cell function. Calcif Tissue Int. 94:98–111. 2014. View Article : Google Scholar

14 

Sun K, Jiang J, Wang Y, Sun X, Zhu J, Xu X, Sun J and Shi J: The role of nerve fibers and their neurotransmitters in regulating intervertebral disc degeneration. Ageing Res Rev. 81:1017332022. View Article : Google Scholar : PubMed/NCBI

15 

Xu H, Li J, Fei Q and Jiang L: Contribution of immune cells to intervertebral disc degeneration and the potential of immunotherapy. Connect Tissue Res. 64:413–427. 2023. View Article : Google Scholar : PubMed/NCBI

16 

Song C, Zhou Y, Cheng K, Liu F, Cai W, Zhou D, Chen R, Shi H, Fu Z, Chen J and Liu Z: Cellular senescence-molecular mechanisms of intervertebral disc degeneration from an immune perspective. Biomed Pharmacother. 162:1147112023. View Article : Google Scholar

17 

Risbud MV and Shapiro IM: Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nat Rev Rheumatol. 10:44–56. 2014. View Article : Google Scholar

18 

Sun Z, Liu ZH, Chen YF, Zhang YZ, Wan ZY, Zhang WL, Che L, Liu X, Wang HQ and Luo ZJ: Molecular immunotherapy might shed a light on the treatment strategies for disc degeneration and herniation. Med Hypotheses. 81:477–480. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Tang T, He Z, Zhu Z, Wang F, Chen H, Zhang F, Zhou J, Wang J, Li B, Liu X, et al: Identification of novel gene signatures and immune cell infiltration in intervertebral disc degeneration using bioinformatics analysis. Front Mol Biosci. 10:11697182023. View Article : Google Scholar : PubMed/NCBI

20 

Zhang Y, Zhang J, Sun Z, Wang H, Ning R, Xu L, Zhao Y, Yang K, Xi X and Tian J: MAPK8 and CAPN1 as potential biomarkers of intervertebral disc degeneration overlapping immune infiltration, autophagy, and ceRNA. Front Immunol. 14:11887742023. View Article : Google Scholar : PubMed/NCBI

21 

Chen LG, Tubbs JD, Liu Z, Thach TQ and Sham PC: Mendelian randomization: Causal inference leveraging genetic data. Psychol Med. 54:1461–1474. 2024. View Article : Google Scholar : PubMed/NCBI

22 

Fang A, Zhao Y, Yang P, Zhang X and Giovannucci EL: Vitamin D and human health: Evidence from Mendelian randomization studies. Eur J Epidemiol. 39:467–490. 2024. View Article : Google Scholar : PubMed/NCBI

23 

Swanson SA, Labrecque J and Hernán MA: Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable? Eur J Epidemiol. 33:723–728. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Evans DM and Davey Smith G: Mendelian randomization: New applications in the coming age of hypothesis-free causality. Annu Rev Genomics Hum Genet. 16:327–350. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Wang P, Li Z and Ye D: Single-cell RNA-seq analysis reveals the Wnt/Ca2+ signaling pathway with inflammation, apoptosis in nucleus pulposus degeneration. BMC Musculoskelet Disord. 25:3212024. View Article : Google Scholar

26 

Huan T, Rong J, Liu C, Zhang X, Tanriverdi K, Joehanes R, Chen BH, Murabito JM, Yao C, Courchesne P, et al: Genome-wide identification of microRNA expression quantitative trait loci. Nat Commun. 6:66012015. View Article : Google Scholar : PubMed/NCBI

27 

Orrù V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, Sole G, Lai S, Dei M, Mulas A, et al: Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 52:1036–1045. 2020. View Article : Google Scholar : PubMed/NCBI

28 

Burgess S and Thompson SG; CRP CHD Genetics Collaboration: Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 40:755–764. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Bowden J, Del Greco MF, Minelli C, Zhao Q, Lawlor DA, Sheehan NA, Thompson J and Davey Smith G: Improving the accuracy of two-sample summary-data Mendelian randomization: Moving beyond the NOME assumption. Int J Epidemiol. 48:728–742. 2019. View Article : Google Scholar :

30 

Glickman ME, Rao SR and Schultz MR: False discovery rate control is a recommended alternative to Bonferroni-type adjustments in health studies. J Clin Epidemiol. 67:850–857. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Dudbridge F: Polygenic Mendelian randomization. Cold Spring Harb Perspect Med. 11:a0395862021. View Article : Google Scholar

32 

Greco MFD, Minelli C, Sheehan NA and Thompson JR: Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med. 34:2926–2940. 2015. View Article : Google Scholar

33 

Fan C, Wang W, Yu Z, Wang J, Xu W, Ji Z, He W, Hua D, Wang W, Yao L, et al: M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis. J Nanobiotechnology. 22:3012024. View Article : Google Scholar

34 

Lin Z, Xu G, Lu X, Liu S, Zou F, Ma X, Jiang J, Wang H and Song J: Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission. J Nanobiotechnology. 22:2812024. View Article : Google Scholar : PubMed/NCBI

35 

Dai J, Liu J, Shen Y, Zhang B, Li C and Liu Z: Regulation of endoplasmic reticulum stress on autophagy and apoptosis of nucleus pulposus cells in intervertebral disc degeneration and its related mechanisms. PeerJ. 12:e172122024. View Article : Google Scholar : PubMed/NCBI

36 

Gao W, Bao J, Zhang Y, He D, Zhang L, Zhang J, Pan H and Wang D: Injectable kaempferol-loaded fibrin glue regulates the metabolic balance and inhibits inflammation in intervertebral disc degeneration. Sci Rep. 13:200012023. View Article : Google Scholar : PubMed/NCBI

37 

Chen X, Zhang A, Zhao K, Gao H, Shi P, Chen Y, Cheng Z, Zhou W and Zhang Y: The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications. Ageing Res Rev. 98:1023232024. View Article : Google Scholar : PubMed/NCBI

38 

Guo W, Mu K, Geng JC, Xing HY, Dong Y, Liu WD, Wang SC, Shi JX, Xing BR, Zhao JY and Li XM: ATF1 and miR-27b-3p drive intervertebral disc degeneration through the PPARG/NF-κB signaling axis. Commun Biol. 8:7512025. View Article : Google Scholar

39 

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

40 

Rouas R, Merimi M, Najar M, El Zein N, Fayyad-Kazan M, Berehab M, Agha D, Bron D, Burny A, Rachidi W, et al: Human CD8+ CD25+ CD127low regulatory T cells: microRNA signature and impact on TGF-β and IL-10 expression. J Cell Physiol. 234:17459–17472. 2019. View Article : Google Scholar : PubMed/NCBI

41 

Diener C, Keller A and Meese E: Emerging concepts of miRNA therapeutics: From cells to clinic. Trends Genet. 38:613–626. 2022. View Article : Google Scholar : PubMed/NCBI

42 

Ferragut Cardoso AP, Banerjee M, Nail AN, Lykoudi A and States JC: miRNA dysregulation is an emerging modulator of genomic instability. Semin Cancer Biol. 76:120–131. 2021. View Article : Google Scholar : PubMed/NCBI

43 

Vafadar A, Shirazi-Tehrani E, Vosough P, Khalili Alashti S, Kargar Jahromi H, Bagheri Lankarani K, Savardashtaki A and Ehtiati S: Non-coding RNAs in celiac disease. Clin Chim Acta. 576:1204172025. View Article : Google Scholar : PubMed/NCBI

44 

Wang Y, Kang J, Guo X, Zhu D, Liu M, Yang L, Zhang G and Kang X: Intervertebral disc degeneration models for pathophysiology and regenerative therapy-benefits and limitations. J Invest Surg. 35:935–952. 2022. View Article : Google Scholar

45 

Hu A, Xing R, Jiang L, Li Z, Liu P, Wang H, Li X and Dong J: Thermosensitive hydrogels loaded with human-induced pluripotent stem cells overexpressing growth differentiation factor-5 ameliorate intervertebral disc degeneration in rats. J Biomed Mater Res B Appl Biomater. 108:2005–2016. 2020. View Article : Google Scholar : PubMed/NCBI

46 

Kilkenny C, Browne WJ, Cuthill IC, Emerson M and Altman DG: Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol. 8:e10004122010. View Article : Google Scholar : PubMed/NCBI

47 

Griffith JF, Wang YXJ, Antonio GE, Choi KC, Yu A, Ahuja AT and Leung PC: Modified Pfirrmann grading system for lumbar intervertebral disc degeneration. Spine (Phila Pa 1976). 32:E708–E712. 2007. View Article : Google Scholar : PubMed/NCBI

48 

Genedy HH, Humbert P, Laoulaou B, Le Moal B, Fusellier M, Passirani C, Le Visage C, Guicheux J, Lepeltier É and Clouet J: MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration. Adv Drug Deliv Rev. 207:1152142024. View Article : Google Scholar : PubMed/NCBI

49 

Wang Y, Deng M, Wu Y, Zheng C, Zhang F, Guo C, Zhang B, Hu C, Kong Q and Wang Y: A multifunctional mitochondria-protective gene delivery platform promote intervertebral disc regeneration. Biomaterials. 317:1230672025. View Article : Google Scholar : PubMed/NCBI

50 

Xu YQ, Zhang ZH, Zheng YF and Feng SQ: Dysregulated miR-133a mediates loss of type II collagen by directly targeting matrix metalloproteinase 9 (MMP9) in human intervertebral disc degeneration. Spine (Phila Pa 1976). 41:E717–E724. 2016. View Article : Google Scholar

51 

Li X, Xu M, Ding L and Tang J: MiR-27a: A novel biomarker and potential therapeutic target in tumors. J Cancer. 10:2836–2848. 2019. View Article : Google Scholar : PubMed/NCBI

52 

Zhang J, Cao Z, Yang G, You L, Zhang T and Zhao Y: MicroRNA-27a (miR-27a) in solid tumors: A review based on mechanisms and clinical observations. Front Oncol. 9:8932019. View Article : Google Scholar : PubMed/NCBI

53 

Su L, Li R, Zhang Z, Liu J, Du J and Wei H: Identification of altered exosomal microRNAs and mRNAs in Alzheimer's disease. Ageing Res Rev. 73:1014972022. View Article : Google Scholar

54 

Speiser DE, Chijioke O, Schaeuble K and Münz C: CD4+ T cells in cancer. Nat Cancer. 4:317–329. 2023. View Article : Google Scholar : PubMed/NCBI

55 

Sun L, Su Y, Jiao A, Wang X and Zhang B: T cells in health and disease. Signal Transduct Target Ther. 8:2352023. View Article : Google Scholar : PubMed/NCBI

56 

Zhu J, Yamane H and Paul WE: Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol. 28:445–489. 2010. View Article : Google Scholar : PubMed/NCBI

57 

Borst J, Ahrends T, Bąbała N, Melief CJM and Kastenmüller W: CD4+ T cell help in cancer immunology and immunotherapy. Nat Rev Immunol. 18:635–647. 2018. View Article : Google Scholar : PubMed/NCBI

58 

Thomas R, Qiao S and Yang X: Th17/Treg imbalance: Implications in lung inflammatory diseases. Int J Mol Sci. 24:48652023. View Article : Google Scholar : PubMed/NCBI

59 

Sakaguchi S, Mikami N, Wing JB, Tanaka A, Ichiyama K and Ohkura N: Regulatory T cells and human disease. Annu Rev Immunol. 38:541–566. 2020. View Article : Google Scholar : PubMed/NCBI

60 

Churov AV, Mamashov KY and Novitskaia AV: Homeostasis and the functional roles of CD4+ Treg cells in aging. Immunol Lett. 226:83–89. 2020. View Article : Google Scholar : PubMed/NCBI

61 

Wei B, Zhao Y, Li W, Zhang S, Yan M, Hu Z and Gao B: Innovative immune mechanisms and antioxidative therapies of intervertebral disc degeneration. Front Bioeng Biotechnol. 10:10238772022. View Article : Google Scholar : PubMed/NCBI

62 

Dou Y, Zhang Y, Liu Y, Sun X, Liu X, Li B and Yang Q: Role of macrophage in intervertebral disc degeneration. Bone Res. 13:152025. View Article : Google Scholar : PubMed/NCBI

63 

Lee S and Lee W: A review of Mendelian randomization: Assumptions, methods, and application to obesity-related diseases. J Obes Metab Syndr. 34:14–26. 2025. View Article : Google Scholar : PubMed/NCBI

64 

Chen B, Yan Y, Wang H and Xu J: Association between genetically determined telomere length and health-related outcomes: A systematic review and meta-analysis of Mendelian randomization studies. Aging Cell. 22:e138742023. View Article : Google Scholar

65 

Ni F, Liu X and Wang S: Impact of negative emotions and insomnia on sepsis: A mediation Mendelian randomization study. Comput Biol Med. 180:1088582024. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li Q, Zhao C, Jin P and Shen C: miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration. Int J Mol Med 56: 193, 2025.
APA
Li, Q., Zhao, C., Jin, P., & Shen, C. (2025). miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration. International Journal of Molecular Medicine, 56, 193. https://doi.org/10.3892/ijmm.2025.5634
MLA
Li, Q., Zhao, C., Jin, P., Shen, C."miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration". International Journal of Molecular Medicine 56.5 (2025): 193.
Chicago
Li, Q., Zhao, C., Jin, P., Shen, C."miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration". International Journal of Molecular Medicine 56, no. 5 (2025): 193. https://doi.org/10.3892/ijmm.2025.5634
Copy and paste a formatted citation
x
Spandidos Publications style
Li Q, Zhao C, Jin P and Shen C: miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration. Int J Mol Med 56: 193, 2025.
APA
Li, Q., Zhao, C., Jin, P., & Shen, C. (2025). miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration. International Journal of Molecular Medicine, 56, 193. https://doi.org/10.3892/ijmm.2025.5634
MLA
Li, Q., Zhao, C., Jin, P., Shen, C."miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration". International Journal of Molecular Medicine 56.5 (2025): 193.
Chicago
Li, Q., Zhao, C., Jin, P., Shen, C."miR‑27b‑3p modulates CD4+CD39+ Tregs to drive immune‑mediated intervertebraldisc degeneration". International Journal of Molecular Medicine 56, no. 5 (2025): 193. https://doi.org/10.3892/ijmm.2025.5634
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team