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Review Open Access

Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review)

  • Authors:
    • Ruth Ruiz Esparza‑Garrido
    • Miguel Ángel Velázquez‑Flores
  • View Affiliations / Copyright

    Affiliations: Non‑coding RNAs Laboratory, Medical Research Unit in Human Genetics, Children's Hospital ‘Dr. Silvestre Frenk Freund’, National Medical Center XXI Century, Mexican Institute of Social Security, Mexico City 06720, Mexico
    Copyright: © Esparza‑Garrido et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 285
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    Published online on: August 11, 2025
       https://doi.org/10.3892/mmr.2025.13650
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Abstract

Non‑coding RNAs are a diverse group of RNAs that are generally not translated into proteins, and control gene expression and other cellular processes through a myriad of mechanisms. Non‑coding RNAs are fragmented to regulate cellular processes such as ribosomal RNA maturation, reverse transcription and degradation of nascent transcripts, among other functions. Non‑coding RNAs and their fragments interact with Toll‑like receptors (TLRs) to induce the activation of the innate and adaptative immune system, which are important for counteracting viral and bacterial infections as well as for triggering ischemia‑related cytotoxic effects in the brain. As the study of these interactions progresses, novel functions are being elucidated, such as their participation in viral reactivation in the brain. Due to their importance as pattern recognition receptor families, TLRs may be potential therapeutic targets for the treatment of autoimmune diseases, viral diseases and cancer. TLR activators are currently used for the treatment of different types of cancer and several other biomolecules are still under investigation to progress towards clinical use. The ncRNAs and their fragments also function as ligands for TLRs, but further study of non‑coding RNAs and their action on TLRs will allow the elucidation of new TLR agonists and antagonists to establish successful immunotherapies. The aim of the present review is to show the existing evidence on TLR activation by ncRNAs and their fragments, with special emphasis on the diseases in which they are involved and on the potential of the study of these interactions for the identification of therapeutic targets and development of therapies. 
View Figures

Figure 1

miRNAs secreted by cortical neurons
activate TLRs 7 and 8 and induced neuronal damage (6,89).
(A) Apoptotic cortical neurons induce the secretion of specific
miRNAs, which activate particular TLRs in vitro. (B)
Incubation of microglia and macrophage cell cultures with miRNAs
secreted by cortical neurons have a neurotoxic effect. (C) The
miRs-100-5p, −298-5p and let-7g-5p are secreted by cortical neurons
and internalized by microglia. These miRNAs activate endosomal
TLR8, induce apoptosis and decrease cell viability. (D) The miRNAs
secreted by cortical neurons act on neuronal TLRs 7 and 8 to
decrease neuronal viability by increasing apoptosis. This effect
was markedly greater in the presence of microglia. (E) In
vivo, intrathecally injected miRNAs increase apoptosis of
cortical neurons and consequently cause a decrease in neuronal
number. TLR, toll-like receptor; miRNA, microRNA; SEAP, secreted
embryonic alkaline phosphatase.

Figure 2

Circulating RNY expression in
pilocytic and diffuse astrocytoma. (A) Pilocytic vs. control
samples. (B) Diffuse vs. control samples. (C) Pilocytic vs. diffuse
samples. RNYs are a class of non-coding RNAs that are components of
the Ro60 ribonucleoprotein particle. Data obtained from
Rodríguez-Corona et al (10).

Figure 3

Predicted functions for circulating
RNYs in pediatric patients with astrocytoma. Differential
expression of the four human RNYs was detected in exosomes of
pediatric patients with astrocytoma. Bioinformatic analyses
indicate that RNYs potentially interact with various protein
receptors. The establishment of protein-protein interaction
networks for these receptors [HIPPIE database
(cbdm-01.zdv.uni-mainz.de/~mschaefer/hippie)] and subsequent
analysis with the PANTHER database (pantherdb.org) showed the
potential involvement of RNYs-receptors in the control of
apoptosis, angiogenesis, cholecystokinin receptor and p53 signaling
pathways, and in Parkinson's disease. RNYs are a class of
non-coding RNAs that are components of the Ro60 ribonucleoprotein
particle. Data obtained from Rodríguez-Corona et al
(10). The data were analyzed with
the Hippie and Panther databases. Interactome images were obtained
from the Hippie database.
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Copy and paste a formatted citation
Spandidos Publications style
Esparza‑Garrido RR and Velázquez‑Flores MÁ: Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review). Mol Med Rep 32: 285, 2025.
APA
Esparza‑Garrido, R.R., & Velázquez‑Flores, M.Á. (2025). Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review). Molecular Medicine Reports, 32, 285. https://doi.org/10.3892/mmr.2025.13650
MLA
Esparza‑Garrido, R. R., Velázquez‑Flores, M. Á."Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review)". Molecular Medicine Reports 32.4 (2025): 285.
Chicago
Esparza‑Garrido, R. R., Velázquez‑Flores, M. Á."Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review)". Molecular Medicine Reports 32, no. 4 (2025): 285. https://doi.org/10.3892/mmr.2025.13650
Copy and paste a formatted citation
x
Spandidos Publications style
Esparza‑Garrido RR and Velázquez‑Flores MÁ: Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review). Mol Med Rep 32: 285, 2025.
APA
Esparza‑Garrido, R.R., & Velázquez‑Flores, M.Á. (2025). Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review). Molecular Medicine Reports, 32, 285. https://doi.org/10.3892/mmr.2025.13650
MLA
Esparza‑Garrido, R. R., Velázquez‑Flores, M. Á."Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review)". Molecular Medicine Reports 32.4 (2025): 285.
Chicago
Esparza‑Garrido, R. R., Velázquez‑Flores, M. Á."Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review)". Molecular Medicine Reports 32, no. 4 (2025): 285. https://doi.org/10.3892/mmr.2025.13650
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