The expression profile and clinical relevance of miR-125a-5p in individuals with chronic periodontitis
DOI:
https://doi.org/10.2340/aos.v85.45028Keywords:
Chronic periodontitis, miR-125a-5p, BTG2, oxidative stress, inflammationAbstract
Background: Chronic periodontitis is a prevalent inflammatory disease, and miR-125a-5p’s role in its pathogenesis remains unclear.
Objective: We examined the clinical significance and mechanisms of miR-125a-5p in chronic periodontitis by testing two hypotheses: (1) miR-125a-5p expression is altered in chronic periodontitis and correlates with clinical indicators; (2) miR-125a-5p regulates periodontal ligament fibroblast (PDLF) functions by targeting specific genes, contributing to disease pathogenesis.
Method: Pearson correlation analysis assessed the association between miR-125a-5p expression and key clinical indicators. Receiver operating characteristic (ROC) curve analysis evaluated its diagnostic performance in chronic periodontitis. Periodontal ligament fibroblasts were treated with lipopolysaccharide (LPS) to establish an inflammatory model. miR-125a-5p and B-cell translocation gene 2 (BTG2) expression levels were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell count kit-8 (CCK-8) assay and enzyme-linked immunosorbent assay (ELISA) assessed miR-125a-5p’s effects on cell proliferation, oxidative stress, and inflammation. The direct interaction between miR-125a-5p and BTG2 was confirmed using a dual-luciferase reporter assay.
Results: The expression level of miR-125a-5p in the gingival crevicular fluid of patients with chronic periodontitis was significantly upregulated and positively correlated with the severity of periodontal tissue damage. In the LPS-induced PDLFs model, miR-125a-5p expression was upregulated, cell proliferation capacity was suppressed, oxidative stress was induced, and levels of inflammation-related factors were increased. Notably, transfection with a miR-125a-5p inhibitor effectively reversed these effects. Moreover, the study confirmed that BTG2 is a direct target gene of miR-125a-5p, and that miR-125a-5p exerts its regulatory effects on cellular functions through targeting BTG2.
Conclusion: miR-125a-5p is potentially associated with chronic periodontitis, and may serve as a therapeutic target.
Downloads
References
Petersen PE, Baehni PC. Periodontal health and global public health. Periodontol 2000. 2012;60:7–14. https://doi.org/10.1111/j.1600-0757.2012.00452.x DOI: https://doi.org/10.1111/j.1600-0757.2012.00452.x
Yucel-Lindberg T, Bage T. Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med. 2013;15:e7. https://doi.org/10.1017/erm.2013.8 DOI: https://doi.org/10.1017/erm.2013.8
Jensen A, Ladegaard Gronkjaer L, Holmstrup P, Vilstrup H, Kilian M. Unique subgingival microbiota associated with periodontitis in cirrhosis patients. Sci Rep. 2018;8:10718. https://doi.org/10.1038/s41598-018-28905-w DOI: https://doi.org/10.1038/s41598-018-28905-w
Tonetti MS, Sanz M. Implementation of the new classification of periodontal diseases: decision-making algorithms for clinical practice and education. J Clin Periodontol. 2019;46:398–405. https://doi.org/10.1111/jcpe.13104 DOI: https://doi.org/10.1111/jcpe.13104
Heitz-Mayfield LJA. Conventional diagnostic criteria for periodontal diseases (plaque-induced gingivitis and periodontitis). Periodontol 2000. 2024;95:10–9. https://doi.org/10.1111/prd.12579 DOI: https://doi.org/10.1111/prd.12579
Jiang F, Zhou Y, Zhang R, Wen Y. miR-205 and HMGB1 expressions in chronic periodontitis patients and their associations with the inflammatory factors. Am J Transl Res. 2021;13:9224–32.
Wang L, Li Y, Hong F, Ning H. Circ_0062491 alleviates LPS-induced apoptosis and inflammation in periodontitis by regulating miR-498/SOCS6 axis. Innate Immun. 2022;28:174–84. https://doi.org/10.1177/17534259211072302 DOI: https://doi.org/10.1177/17534259211072302
Yao D, Zhou Z, Wang P, Zheng L, Huang Y, Duan Y, et al. MiR-125-5p/IL-6R axis regulates macrophage inflammatory response and intestinal epithelial cell apoptosis in ulcerative colitis through JAK1/STAT3 and NF-kappaB pathway. Cell Cycle. 2021;20:2547–64. https://doi.org/10.1080/15384101.2021.1995128 DOI: https://doi.org/10.1080/15384101.2021.1995128
Sun L, Lian JX, Meng S. MiR-125a-5p promotes osteoclastogenesis by targeting TNFRSF1B. Cell Mol Biol Lett. 2019;24:23. https://doi.org/10.1186/s11658-019-0146-0 DOI: https://doi.org/10.1186/s11658-019-0146-0
Li JQ, Hu SY, Wang ZY, Lin J, Jian S, Dong YC, et al. MicroRNA-125-5p targeted CXCL13: a potential biomarker associated with immune thrombocytopenia. Am J Transl Res. 2015;7:772–80.
Luan X, Zhou X, Naqvi A, Francis M, Foyle D, Nares S, et al. MicroRNAs and immunity in periodontal health and disease. Int J Oral Sci 2018;10:24. https://doi.org/10.1038/s41368-018-0025-y DOI: https://doi.org/10.1038/s41368-018-0025-y
Kim SH, Jung IR, Hwang SS. Emerging role of anti-proliferative protein BTG1 and BTG2. BMB Rep. 2022;55:380–8. https://doi.org/10.5483/BMBRep.2022.55.8.092 DOI: https://doi.org/10.5483/BMBRep.2022.55.8.092
Boiko AD, Porteous S, Razorenova OV, Krivokrysenko VI, Williams BR, Gudkov AV. A systematic search for downstream mediators of tumor suppressor function of p53 reveals a major role of BTG2 in suppression of Ras-induced transformation. Genes Dev. 2006;20:236–52. https://doi.org/10.1101/gad.1372606 DOI: https://doi.org/10.1101/gad.1372606
Kawakubo H, Brachtel E, Hayashida T, Yeo G, Kish J, Muzikansky A, et al. Loss of B-cell translocation gene-2 in estrogen receptor- positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein. Cancer Res. 2006;66:7075–82. https://doi.org/10.1158/0008-5472.CAN-06-0379 DOI: https://doi.org/10.1158/0008-5472.CAN-06-0379
Wang Q, Jiang F, Zhao C, Song J, Hu M, Lv Y, et al. miR-21-5p prevents doxorubicin-induced cardiomyopathy by downregulating BTG2. Heliyon. 2023;9:e15451. https://doi.org/10.1016/j.heliyon.2023.e15451 DOI: https://doi.org/10.1016/j.heliyon.2023.e15451
Pan B, Teng Y, Wang R, Chen D, Chen H. Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease. BMC Med Genomics. 2024;17:152. https://doi.org/10.1186/s12920-024-01915-6 DOI: https://doi.org/10.1186/s12920-024-01915-6
Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, et al. Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018;89(Suppl 1):S173–S82.
Du Y, Qi YS, Chen H, Shen G. The expression and clinical significance of miR-1226 in patients with periodontitis. BMC Oral Health. 2021;21:487. https://doi.org/10.1186/s12903-021-01855-y DOI: https://doi.org/10.1186/s12903-021-01855-y
Bardou P, Mariette J, Escudie F, Djemiel C, Klopp C. jvenn: an interactive Venn diagram viewer. BMC Bioinform. 2014;15:293. https://doi.org/10.1186/s12903-021-01855-y DOI: https://doi.org/10.1186/1471-2105-15-293
Petersen PE, Ogawa H. The global burden of periodontal disease: towards integration with chronic disease prevention and control. Periodontol 2000. 2012;60:15–39. https://doi.org/10.1111/j.1600-0757.2011.00425.x DOI: https://doi.org/10.1111/j.1600-0757.2011.00425.x
Li S, Liu X, Zhou Y, Acharya A, Savkovic V, Xu C, et al. Shared genetic and epigenetic mechanisms between chronic periodontitis and oral squamous cell carcinoma. Oral Oncol. 2018;86:216–24. https://doi.org/10.1016/j.oraloncology.2018.09.029 DOI: https://doi.org/10.1016/j.oraloncology.2018.09.029
Shin YJ, Choung HW, Lee JH, Rhyu IC, Kim HD. Association of periodontitis with oral cancer: a case-control study. J Dent Res. 2019;98:526–33. https://doi.org/10.1177/0022034519827565 DOI: https://doi.org/10.1177/0022034519827565
Wu P, Feng J, Wang W. Expression of miR-155 and miR-146a in the saliva of patients with periodontitis and its clinical value. Am J Transl Res. 2021;13:6670–7. https://doi.org/10.1155/2021/5135278 DOI: https://doi.org/10.1155/2021/5135278
Steigmann L, Maekawa S, Sima C, Travan S, Wang CW, Giannobile WV. Biosensor and lab-on-a-chip biomarker-identifying technologies for oral and periodontal diseases. Front Pharmacol. 2020;11:588480. https://doi.org/10.3389/fphar.2020.588480 DOI: https://doi.org/10.3389/fphar.2020.588480
Agrawal P, Sanikop S, Patil S. New developments in tools for periodontal diagnosis. Int Dent J. 2012;62:57–64. https://doi.org/10.1111/j.1875-595X.2011.00099.x DOI: https://doi.org/10.1111/j.1875-595X.2011.00099.x
Dos Santos MP, Pereira JN, De Labio RW, Carneiro LC, Pontes JC, Barbosa MS, et al. Decrease of miR-125a-5p in gastritis and gastric cancer and its possible association with H. pylori. J Gastrointest Cancer 2021;52:569–74. https://doi.org/10.1007/s12029-020-00432-w DOI: https://doi.org/10.1007/s12029-020-00432-w
Murata K, Furu M, Yoshitomi H, Ishikawa M, Shibuya H, Hashimoto M, et al. Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis. PLoS One. 2013;8:e69118. https://doi.org/10.1371/journal.pone.0069118 DOI: https://doi.org/10.1371/journal.pone.0069118
Liang Y, Ye J, Jiao J, Zhang J, Lu Y, Zhang L, et al. Down-regulation of miR-125a-5p is associated with salivary adenoid cystic carcinoma progression via targeting p38/JNK/ERK signal pathway. Am J Transl Res. 2017;9:1101–13.
Cheng L, Fan Y, Cheng J, Wang J, Liu Q, Feng Z. Long non-coding RNA ZFY-AS1 represses periodontitis tissue inflammation and oxidative damage via modulating microRNA-129-5p/DEAD-Box helicase 3 X-linked axis. Bioengineered. 2022;13:12691–705. https://doi.org/10. 1080/21655979.2021.2019876 DOI: https://doi.org/10.1080/21655979.2021.2019876
Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180–3. https://doi.org/10.1016/j.redox.2015.01.002 DOI: https://doi.org/10.1016/j.redox.2015.01.002
Sczepanik FSC, Grossi ML, Casati M, Goldberg M, Glogauer M, Fine N, et al. Periodontitis is an inflammatory disease of oxidative stress: we should treat it that way. Periodontol 2000. 2020;84:45–68. https://doi.org/10.1111/prd.12342 DOI: https://doi.org/10.1111/prd.12342
Mohideen K, Chandrasekar K, Ramsridhar S, Rajkumar C, Ghosh S, Dhungel S. Assessment of oxidative stress by the estimation of lipid peroxidation marker malondialdehyde (MDA) in patients with chronic periodontitis: a systematic review and meta-analysis. Int J Dent. 2023;2023:6014706. https://doi.org/10.1155/2023/6014706 DOI: https://doi.org/10.1155/2023/6014706
Neurath N, Kesting M. Cytokines in gingivitis and periodontitis: from pathogenesis to therapeutic targets. Front Immunol. 2024;15:1435054. https://doi.org/10.3389/fimmu.2024.1435054 DOI: https://doi.org/10.3389/fimmu.2024.1435054
Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci. 2019;11:30. https://doi.org/10.1038/s41368-019-0064-z DOI: https://doi.org/10.1038/s41368-019-0064-z
Zhang Z, Zhang Y, Cai Y, Li D, He J, Feng Z, et al. NAT10 regulates the LPS-induced inflammatory response via the NOX2-ROS-NF-kappaB pathway in macrophages. Biochim Biophys Acta Mol Cell Res. 2023;1870:119521. https://doi.org/10.1016/j.bbamcr.2023.119521 DOI: https://doi.org/10.1016/j.bbamcr.2023.119521
Xu W, Chen X, Wang Y, Fan B, Guo K, Yang C, et al. Chitooligosaccharide inhibits RANKL-induced osteoclastogenesis and ligation-induced periodontitis by suppressing MAPK/ c-fos/NFATC1 signaling. J Cell Physiol. 2020;235:3022–32. https://doi.org/10.1002/jcp.29207 DOI: https://doi.org/10.1002/jcp.29207
Mao B, Zhang Z, Wang G. BTG2: a rising star of tumor suppressors (review). Int J Oncol. 2015;46:459–64. https://doi.org/10.3892/ijo.2014.2765 DOI: https://doi.org/10.3892/ijo.2014.2765
Published
Issue
Section
License
Copyright (c) 2026 Senqiang Li, Baoqing Fang, Qian Sun

This work is licensed under a Creative Commons Attribution 4.0 International License.
Acta Odontologica Scandinavica publishes high quality original research papers as well as critical reviews relevant on diseases of the oral cavity, their treatment, epidemiology and associated biomaterials and their development.