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

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.