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Noncoding RNAs in periodontitis: Progress and perspectives (Review)

  • Authors:
    • Yuanyi Feng
    • Xiaolan Guo
    • Yumeng Yang
    • Wei Qiu
    • Zhao Chen
    • Fuchun Fang
  • View Affiliations / Copyright

    Affiliations: Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
    Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 166
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    Published online on: August 11, 2025
       https://doi.org/10.3892/ijmm.2025.5607
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Abstract

Periodontitis is the sixth most common chronic non‑infectious disease in the world. It mainly leads to the inflammatory destruction of periodontal supporting tissue, which has become the main cause of tooth loss in adults. Periodontitis is also a risk factor for various systemic diseases. Noncoding ribonucleic acids (ncRNAs) are important regulators of normal biological processes and their abnormal expression has been shown to be important to the pathogenesis of inflammatory diseases, including periodontitis. Biologically, they can regulate immune inflammation, bone homeostasis and cell proliferation in periodontitis. Clinically, they are promising diagnostic markers and therapeutic targets. Recent advances in technology have opened up new directions for the study of ncRNAs, including RNA secondary structures, RNA protein interactions, ncRNA‑encoded peptides or proteins and single‑cell RNA sequencing. Therefore, the present study summarized the function and mechanisms of ncRNAs in periodontitis, as well as their clinical potential for diagnosis and treatment and highlight these exciting areas of research.
View Figures

Figure 1

Graphical Abstract. Brief overview of
ncRNAs in periodontitis. NcRNAs not only regulate immune
inflammation, bone homeostasis and cell proliferation in
periodontitis, but also serve as diagnostic marker and nucleic acid
drug. nc, noncoding; GCF, gingival crevicular fluid.

Figure 2

Brief overview of ncRNAs regulate
immune inflammation in periodontitis. LncRNA PTCSC3 can
downregulate TLR4 and lncRNA MFG-AS1 was found to upregulate
TLR4. LncRNA NEAT1, lncRNA ZFY-AS1, lncRNA MALAT1,
Linc01126, Circ_0138959, CircPVT1, Linc00616 and
Circ_0099630 are markedly increased in the pathogenesis of
periodontitis, which targeting miRNA and upregulating target
proteins and then which promoting the occurrence and development of
periodontal disease. LncRNA LOXL1-AS1, LncRNA SNHG5,
Circ_0003948, Circ_0062491, Circ_0085289 are
down-regulated in the pathogenesis of periodontitis and play a
protective role in periodontitis. The black arrowheads indicate
promotion and the red T indicate inhibition. nc, noncoding; lnc,
long noncoding; linc, long intergenic noncoding; circ, circular;
mi, micro; TLR4, Toll-like receptor 4; TRAF6, TNF
receptor-associated factor 6; Bax, Bcl-2-associated X protein;
Bcl-2, B-cell lymphoma 2; DDX3X, DEAD-box helicase 3 X-linked;
NF-κB, nuclear factor kappa-B; HIF-1α, hypoxia inducible factor 1
alpha; MAPK, mitogen-activated protein kinase; JAK2, Janus kinase
2; STAT3, signal transducer and activator of transcription 3;
NR2F2, nuclear receptor subfamily 2 group F member 2; PTEN,
phosphatase and tensin homolog; NRF-2, nuclear factor
(erythroid-derived 2)-like 2; HO-1, heme oxygenase-1; TFRC,
transferrin receptor; LfR, lactoferrin receptor; SOCS6, suppressor
of cytokine signaling 6.

Figure 3

NcRNAs regulate bone homeostasis in
periodontitis. LncRNAs and circRNAs promote the osteogenic
differentiation of PDLSCs and bone resorption of osteoclasts by
adsorbing miRNAs as ceRNAs. The black arrowheads indicate promotion
and the red T indicate inhibition. nc, noncoding; lnc, long
noncoding; Linc, long intergenic noncoding; circ, circular; PDLSCs,
periodontal ligament stem cells; mi, micro; ce, competing
endogenous; SMAD6, mothers against decapentaplegic homolog 6;
IGF-1R, insulin-like growth factor 1 receptor; HIF-1α, hypoxia
inducible factor 1 alpha; MAPK, mitogen-activated protein kinase;
HES1, hes family BHLH transcription factor 1; PLAP-1,
periodontal-ligament–associated protein-1; ETS1, erythroblast
transformation specific 1; FOXO1, forkhead box O1; RO60, Y RNA
binding protein; BGLAP, bone gamma-carboxyglutamate protein; FGFR1,
fibroblast growth factor receptor 1; IGF1, insulin-like growth
factor 1; AKT, protein kinase B; IKK, inhibitor of NF-κB kinase;
NF-κB, nuclear factor kappa-B; C/EBP-β, CCAAT-enhancer-binding
protein-β; NLRP3, NLR family pyrin domain containing 3; CHRDL1,
chordin like 1; BMP7, bone morphogenetic protein 7; SMAD5, mothers
against decapentaplegic homolog 5; RUNX2, runt-related
transcription factor 2; Zeb2, zinc finger E-box binding homeobox 2;
TRAF6, TNF receptor-associated factor 6.

Figure 4

NcRNAs regulate the proliferation of
PDLSCs/PDLCs. From left to right of figure shows PDLSCs/PDLCs
proliferation. The gray area is the ncRNA that promotes the
proliferation of PDLSCs/PDLCs and the yellow area is the ncRNA that
inhibits the proliferation of PDLSCs/PDLCs. The black arrowheads
indicate promotion and the red T indicate inhibition. Bold red
arrowheads indicate the molecules with increased/decreased
expression of ncRNA in the process of promoting/inhibiting cell
proliferation. nc, noncoding; PDLSCs, periodontal ligament stem
cells; PDLCs, periodontal ligament cells; YAP1, yes-associated
protein 1; FGF2, fibroblast growth factor 2; TLR4, Toll-like
receptor 4; PLAP-1, periodontal-ligament-associated protein-1;
CDK4, cyclin-dependent kinase 4; CDK6, cyclin-dependent kinase 6;
CCND-1, cyclin D1; SPRY1, sprouty RTK signaling antagonist 1; ERK,
extracellular signal-regulated kinase.

Figure 5

ROC curve was used to screen
biomarkers for early diagnosis of the disease. Firstly, the
predicted ncRNA biomarkers were obtained by RNA-seq or database
analysis. ROC curve was used to evaluate the reliability of
diagnostic biomarkers. The biomarker can be verified clinically to
evaluate its diagnostic efficacy. If the biomarker is reliable, it
can be prepared as a drug for disease diagnosis. ROC, receiver
operating characteristic; nc, noncoding; RNA-seq, RNA-sequences;
GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes;
GCF, gingival crevicular fluid; RT-qPCR, reverse transcription
quantitative PCR.

Figure 6

Diagnostic potential of ncRNA in
periodontitis. NcRNAs in human tissues or various types of body
fluids (including serum and urine) can be used as diagnostic
markers for systemic diseases. Similarly, different samples such as
serum, saliva and GCF can also be used as sources of ncRNAs, which
could be used as potential biomarkers. nc, noncoding; GCF, gingival
crevicular fluid.

Figure 7

Therapeutic potential of ncRNAs. (A)
Nucleic acid delivery systems deliver ncRNA for the treatment of
digestive, respiratory and circulatory system diseases. (B) Animal
researches on ncRNA as nucleic acid drugs for disease treatment.
(C) The advantages of ncRNA carriers (exosomes, lipid
nanoparticles, polymer nanoparticles). nc, noncoding.
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Copy and paste a formatted citation
Spandidos Publications style
Feng Y, Guo X, Yang Y, Qiu W, Chen Z and Fang F: Noncoding RNAs in periodontitis: Progress and perspectives (Review). Int J Mol Med 56: 166, 2025.
APA
Feng, Y., Guo, X., Yang, Y., Qiu, W., Chen, Z., & Fang, F. (2025). Noncoding RNAs in periodontitis: Progress and perspectives (Review). International Journal of Molecular Medicine, 56, 166. https://doi.org/10.3892/ijmm.2025.5607
MLA
Feng, Y., Guo, X., Yang, Y., Qiu, W., Chen, Z., Fang, F."Noncoding RNAs in periodontitis: Progress and perspectives (Review)". International Journal of Molecular Medicine 56.5 (2025): 166.
Chicago
Feng, Y., Guo, X., Yang, Y., Qiu, W., Chen, Z., Fang, F."Noncoding RNAs in periodontitis: Progress and perspectives (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 166. https://doi.org/10.3892/ijmm.2025.5607
Copy and paste a formatted citation
x
Spandidos Publications style
Feng Y, Guo X, Yang Y, Qiu W, Chen Z and Fang F: Noncoding RNAs in periodontitis: Progress and perspectives (Review). Int J Mol Med 56: 166, 2025.
APA
Feng, Y., Guo, X., Yang, Y., Qiu, W., Chen, Z., & Fang, F. (2025). Noncoding RNAs in periodontitis: Progress and perspectives (Review). International Journal of Molecular Medicine, 56, 166. https://doi.org/10.3892/ijmm.2025.5607
MLA
Feng, Y., Guo, X., Yang, Y., Qiu, W., Chen, Z., Fang, F."Noncoding RNAs in periodontitis: Progress and perspectives (Review)". International Journal of Molecular Medicine 56.5 (2025): 166.
Chicago
Feng, Y., Guo, X., Yang, Y., Qiu, W., Chen, Z., Fang, F."Noncoding RNAs in periodontitis: Progress and perspectives (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 166. https://doi.org/10.3892/ijmm.2025.5607
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