The mechanistic role of non-coding RNAs in febrile seizures in children: their potential as biomarkers and therapeutic targets—a systematic review

Introduction

Febrile seizures (FSs) are characterized by convulsions, occurring in infants and young children, typically between the ages of 6 months and 5 years, and are associated with an elevated body temperature. They are the most common type of seizure in this age group, affecting approximately 2–5% of children globally (1). The epidemiology of FSs indicates a higher prevalence in men and those with a family history of seizures, highlighting a potential genetic predisposition (2). FSs can be classified into two main categories: simple and complex. Simple FSs are characterized by generalized tonic-clonic activity lasting less than 15 min and occurring only once within a 24-h period. In contrast, complex FSs may be focal, lasting longer, or recurring within the same febrile episode (3). Clinically, FSs can manifest with symptoms, such as loss of consciousness, jerking movements, and postictal confusion, which may vary depending on the type and duration of the seizure (4).

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not encode proteins, while they play notable roles in gene regulation and cellular processes. They include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and small interfering RNAs (siRNAs). These molecules are essential for various biological functions, including transcriptional regulation, chromatin remodeling, and post-transcriptional modifications, thereby influencing cellular behavior and development (5). Recent research highlighted the significant impact of ncRNAs on neurological disorders, demonstrating that they may play a role in the pathophysiology of FSs (6).

Despite the absence of specific studies in the PubMed database directly linking ncRNAs to pediatric FSs, the broader involvement of ncRNAs in various neurological disorders highlights the need for further research in this area. Recent studies have highlighted the involvement of various ncRNAs, including microRNAs and long non-coding RNAs, in the regulation of gene expression related to neuronal excitability and synaptic plasticity, both of which are crucial in the pathophysiology of seizures (7,8). For instance, alterations in the expression levels of specific microRNAs have been linked to increased seizure susceptibility and altered neuronal function (9). Additionally, long non-coding RNAs have exhibited to play roles in modulating inflammatory responses in the brain, which may further influence seizure activity. Understanding these mechanisms may unveil novel pathways that contribute to FSs, paving the way for innovative therapeutic strategies.

The decision to concentrate this review on ncRNAs, rather than the well-established roles of cytokines or ion channels, is on the basis of their unique function as master regulators. While cytokines and ion channel dysfunction are recognized as direct contributors to FS pathogenesis, emerging evidence demonstrates that ncRNAs can modulate these processes. Specific miRNAs can post-transcriptionally regulate the expression levels of multiple cytokine genes and ion channel subunits simultaneously (10). This integrative regulatory capacity positions ncRNAs as upstream of these traditional factors, potentially providing a more holistic understanding of FS pathophysiology. Thus, investigating ncRNAs may uncover unifying molecular mechanisms and novel therapeutic targets that address entire dysregulated networks, rather than concentrating on single proteins.

Moreover, the potential of ncRNAs as biomarkers for FSs cannot be overlooked. Their stability in biological fluids makes them attractive candidates for non-invasive diagnostic tools. Future studies should concentrate on profiling ncRNA expression in pediatric patients with FSs compared with healthy controls to identify specific ncRNAs, correlating with seizure frequency, duration, and response to treatment. We present this article in accordance with the PRISMA reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-15/rc).

Methods

Literature search and selection strategy

The literature search methodology employed for this review was systematically outlined, including the specified date range of the search. A detailed list of the electronic databases utilized, including PubMed, Web of Science, and Embase, was provided. A systematically constructed set of keyword combinations was employed to ensure thorough coverage of literature related to “Febrile Seizures” and “non-coding RNA”. The stepwise process for literature screening was clearly outlined, involving stages of initial screening, full-text assessment, and final inclusion, with justifications for exclusions at each stage (Figure 1).

Figure 1 Flow diagram of the literature search and study selection process. FS, febrile seizure; ncRNA, non-coding RNAs.

Results

Pathophysiological mechanisms of pediatric FSs

Developmental characteristics of the nervous system

The nervous system of children is characterized by ongoing development and maturation, playing a crucial role in the incidence and characteristics of FSs. During early childhood, the brain undergoes significant changes, including synaptogenesis, myelination, and establishment of neural circuits. This developmental plasticity can make the immature brain more susceptible to seizures during febrile episodes. Studies have demonstrated that the excitability of neural networks in young children is heightened, which may contribute to the increased incidence of FSs in this population compared with adults (11,12). Additionally, the balance between excitatory and inhibitory neurotransmission is still developing in young children, making them more susceptible to seizure activity in response to fever, which frequently arises from infections. This unique developmental framework is essential for understanding why FSs are more common in younger children, particularly those aging under 5 years old, and highlights the importance of age-related neurophysiological factors in the pathophysiology of FSs (13).

Relationship between immune response and FSs

The immune response plays a significant role in the occurrence of FSs. Fever, a common response to infection, is mainly accompanied by an inflammatory response that can affect neural excitability. Studies demonstrated that pro-inflammatory cytokines released during infections can influence neuronal activity and potentially lower the seizure threshold (14,15). Notably, the expression levels of these key cytokines are themselves tightly regulated by specific ncRNAs. For instance, miR-146a serves as a critical negative feedback regulator that attenuates the IL-1β-driven inflammatory response, while miR-155 promotes the production of TNF-α and IL-6. Dysregulation of these miRNAs may, therefore, exacerbate neuroinflammation and lower the seizure threshold during febrile episodes. Furthermore, the interaction between the immune system and the central nervous system (CNS) is critical, as neuroinflammation can lead to alterations in neural circuits that predispose children to seizures during febrile episodes. Understanding these immunological mechanisms provides insights into potential therapeutic targets for preventing recurrent FSs, particularly in children with a history of FSs (16).

Impact of genetic factors

Genetic factors significantly influence the susceptibility to FSs in children. Various studies have identified specific genetic variants associated with an increased risk of FS, particularly those affecting ion channels and neurotransmitter systems. Beyond direct gene mutations, the post-transcriptional regulation of ion channel genes, such as SCN1A by ncRNAs represents another layer of control over neuronal excitability. Studies have demonstrated that miRNAs, such as miR-134 can target SCN1A mRNA, potentially fine-tuning sodium channel density at the membrane. Similarly, the lncRNA BDNF-AS has been implicated in regulating synaptic excitability through mechanisms that may involve ion channel expression. This ncRNA-mediated regulation may contribute to the variable penetrance and expressivity of genetic predispositions to FSs (17,18). Additionally, family history of epilepsy or FSs is a recognized risk factor, suggesting a heritable component to the condition. The interaction between genetic predispositions and environmental factors, such as infections, underscores the complexity of FS pathophysiology. Identifying genetic markers can aid in predicting which children are at a higher risk of recurrent FSs and guide clinical management strategies (19,20). This genetic perspective is essential for a comprehensive understanding of FSs and their recurrence in pediatric populations.

Classification and functions of ncRNAs

Notably, ncRNAs are a diverse group of RNA molecules that do not encode proteins, while they play crucial roles in regulating various biological processes. They are classified into several categories based on their size, structure, and function. Understanding these classifications is therefore essential to elucidate their roles in health and disease.

miRNAs

miRNAs are small non-coding RNA molecules, typically 21-25 nucleotides in length, regulating gene expression post-transcriptionally. They bind to complementary sequences on target messenger RNAs (mRNAs), leading to mRNA degradation or inhibition of translation. MiRNAs are involved in numerous biological processes, including cell proliferation, differentiation, and apoptosis. Dysregulation of miRNA expression is associated with various diseases, particularly diverse cancer types. For instance, certain miRNAs have been identified as potential biomarkers for lung cancer, where their expression profiles can help classify patients and predict outcomes (21). Additionally, prior research demonstrated that specific circulating miRNAs can serve as biomarkers for hepatocellular carcinoma, highlighting their potential in cancer diagnostics (22). The exploration of miRNA-target interactions continues to reveal their complex roles in pathophysiology, making them as a significant concentration of contemporary research in molecular biology and oncology (23).

LncRNAs

LncRNAs are defined as RNA molecules longer than 200 nucleotides that do not encode proteins. They are known to participate in various cellular functions, including chromatin remodeling, transcriptional regulation, and post-transcriptional processing. LncRNAs can modulate gene expression by interacting with DNA, RNA, and proteins, thereby influencing cellular pathways and processes. Their involvement in diseases, particularly in cancer, is of great significance. For instance, lncRNAs have been implicated in the regulation of oncogenes and tumor suppressor genes, affecting cancer progression and metastasis (24). Recent research highlighted the role of lncRNAs in autoimmune diseases and neurological disorders, indicating their widespread impact on human health (25). The complexity of lncRNA interactions and their regulatory mechanisms remains an active area of research, with important implications for therapeutic strategies (26).

Other types of ncRNAs

In addition to miRNAs and lncRNAs, the roles of several other types of ncRNAs, each with distinct functions, are noteworthy. These include small nucleolar RNAs (snoRNAs), which are involved in the chemical modifications of rRNA; siRNAs, playing a role in RNA interference; and enhancer RNAs (eRNAs), which are associated with the regulation of gene transcription at enhancer regions. Emerging research suggests that eRNAs are crucial in mediating transcriptional regulation and may be implicated in various diseases, including cancer (27). Furthermore, ncRNAs are increasingly recognized for their functions in the epigenetic regulation of gene expression, contributing to the understanding of complex diseases (28). The classification and functional analysis of the ncRNAs are essential to unravel their contributions to cellular homeostasis and disease pathology, providing a basis for novel therapeutic approaches (29).

ncRNAs implicated in seizure biology

Beyond their general biological roles, several specific ncRNAs have emerged as key regulators in seizure pathophysiology, forming a critical link to FSs. Among microRNAs, miR-134 has been extensively studied for its role in limiting dendritic spine growth and promoting neuronal hyperexcitability, and its inhibition has shown to suppress seizures in experimental models (30). Concurrently, miR-146a functions as a vital negative feedback regulator of neuroinflammation by targeting adapter proteins in the IL-1β signaling pathway (e.g., IRAK1, TRAF6), while the pro-inflammatory miR-155 amplifies cytokine production and may compromise blood-brain barrier integrity (31). In the context of circular RNAs, circHIPK2 has been identified as a competitive endogenous RNA that sequesters miR-124-3p, thereby regulating astrocyte activation and contributing to an inflammatory microenvironment conducive to seizure generation. The roles of these ncRNAs in core seizure mechanisms, involving synaptic plasticity, neuroinflammation, and glial dysfunction, highlight their potential as prime molecular candidates for elucidating the specific pathogenesis of FS.

Research progress of ncRNAs in FSs

Role of ncRNAs in neurodevelopment

Notably, ncRNAs play a pivotal role in neurodevelopment, influencing various processes, such as neuronal differentiation, synaptic plasticity, and overall brain maturation. Recent studies have highlighted the involvement of specific ncRNAs, including miRNAs and lncRNAs, in regulating genes that are essential for neurogenesis and neuronal function. For instance, circRNAs have exhibited to modulate the expression levels of neurodevelopmental genes, impacting cognitive functions and behavior (32). Moreover, dysregulation of ncRNAs has been found to be associated with neurodevelopmental disorders, indicating their potential as biomarkers and therapeutic targets. The correlation between ncRNAs and signaling pathways during brain development highlights their significance in maintaining neural health and preventing neurodevelopmental abnormalities (33). Understanding the specific roles of ncRNAs in neurodevelopment may provide insights into the pathophysiology of FSs, as alterations in neurodevelopmental processes may contribute to seizure susceptibility.

Relationship between ncRNAs and inflammatory responses

Evidence from rodent models of hyperthermia-induced seizures, which closely resemble human FS, has begun to elucidate the dynamic alterations and specific roles of ncRNAs in this context. The relationship between ncRNAs and inflammatory responses has remarkably garnered scholars’ attention, particularly in the context of neurological disorders. Inflammation is a key factor in the pathogenesis of various conditions, including FSs, where it can exacerbate neuronal excitability and lead to seizure activity. NcRNAs, particularly miRNAs, have been implicated in the regulation of inflammatory pathways. For instance, certain miRNAs can modulate the expression levels of pro-inflammatory cytokines, thereby influencing the neuroinflammatory response (34). Additionally, lncRNAs have exhibited to interact with inflammatory mediators, contributing to the regulation of immune responses in the CNS (35). The dysregulation of ncRNAs in response to inflammatory stimuli may play a pivotal role in the pathogenesis of FSs, highlighting the need for further exploration of their potential as therapeutic targets in managing inflammation-related seizure disorders. While these hyperthermia models provide the most direct evidence, research on other seizure models may provide complementary insights into the conserved functions of these ncRNAs across different forms of seizure activities.

Expression changes of ncRNAs in FS models

Research has demonstrated that the expression of ncRNAs undergoes significant changes in various FS models. These alterations can provide insights into the molecular mechanisms underlying seizure susceptibility and neurodevelopmental outcomes. For instance, prior research reported upregulation of specific miRNAs during FS episodes, which may be associated with neuronal stress and excitotoxicity (36). Furthermore, lncRNAs have been identified as critical regulators of gene expression in response to FSs, potentially influencing neuronal survival and function (37). The characterization of ncRNA expression profiles in FS models not only enhances our understanding of the pathophysiological mechanisms, but also provides novel directions for the development of targeted therapeutic strategies aimed at modulating ncRNA activity to mitigate seizure effects. Ongoing research in this area is essential for elucidating the complex role of ncRNAs in FSs and their potential as biomarkers for seizure prediction and management.

Discussion

The potential of ncRNAs as biomarkers

Stability and detection methods of ncRNAs

Importantly, ncRNAs have emerged as promising biomarkers owing to their stability in various biological fluids, including blood, saliva, and urine. This stability is critical for their potential as diagnostic tools, as it allows for reliable detection and quantification. Various detection methods have been developed to identify and analyze ncRNAs, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), microarrays, and next-generation sequencing (NGS). Each method possesses its advantages and limitations. For instance, qRT-PCR is highly sensitive and specific, while may not capture the full spectrum of ncRNAs present in a sample. The NGS provides comprehensive profiling, whereas requires more complex data analysis and bioinformatics capabilities. Recent advancements in exosomal ncRNA research highlighted the potential of these vesicles as carriers of stable ncRNAs, making them promising candidates for non-invasive diagnostics in diseases, such as cancer and cardiovascular conditions (38,39). Furthermore, the development of novel extraction methods, including the dextran sulfate-based approach, has remarkably improved RNA recovery from biological samples, thereby enhancing the reliability of ncRNA detection (40).

Summary and analysis of related research findings

The growing body of research on ncRNAs has revealed their involvement in various pathological processes, making them potential biomarkers for several diseases. For instance, studies have demonstrated that specific circulating ncRNAs are associated with diabetic nephropathy and cardiovascular diseases, indicating their role in disease progression and response to treatment (41,42). Additionally, ncRNAs, such as miRNAs and lncRNAs, have been implicated in cancer, with distinct expression profiles found in diverse cancer types, including colorectal cancer and prostate cancer (43,44). The ability of ncRNAs to reflect the physiological and pathological states of tissues makes them valuable for the early diagnostic and prognostic assessments. However, the heterogeneity of ncRNA expression and the influence of external factors, such as diet and environment, pose challenges in standardizing their use as biomarkers. Comprehensive studies that correlate ncRNA profiles with clinical outcomes are essential to validate their utility in clinical settings (45,46). Although direct clinical data on circulating ncRNAs in children with FS are currently lacking, a set of promising candidate biomarkers can be proposed based on ncRNAs that play roles in key pathogenic pathways, as elucidated through FS animal models and mechanistic studies (Table 1).

Future research directions and challenges

Despite the promising potential of ncRNAs as biomarkers, several challenges remain that need to be addressed to facilitate their clinical application. One major challenge is the need for standardization in ncRNA detection and quantification methods to ensure reproducibility and comparability across studies. Additionally, further research is essential to elucidate the functional roles of ncRNAs in various diseases, as understanding their mechanisms of action may enhance their biomarker potential (47,48). Another important area to explore is the investigation of ncRNA interactions with other molecular entities, including proteins and other RNAs, which may influence their stability and functionality (49). Furthermore, the integration of ncRNA profiling with other omics technologies, such as genomics and proteomics, could provide a more comprehensive understanding of disease mechanisms and lead to the identification of novel therapeutic targets (50). As the field progresses, overcoming these challenges will be essential for translating ncRNA research into clinical practice, ultimately improving patient outcomes through personalized medicine approaches. However, translating these candidates into clinically useful biomarkers faces significant hurdles, concentrating on issues of sensitivity and specificity. Regarding sensitivity, the abundance, spatiotemporal release dynamics, and half-life of ncRNAs in blood could lead to false negatives. A more critical challenge is specificity: determining whether the alteration patterns of these candidates in circulation can robustly distinguish febrile illness with seizures from febrile illness without seizures, which is essential for the differential diagnosis of FS. Future studies must address these issues systematically through rigorous longitudinal cohort designs and multi-omics integration.

Application prospects of RNAs in the treatment of FSs

The potential of ncRNA as a therapeutic target

Notably, ncRNAs have emerged as crucial regulators in various biological processes, including the pathophysiology of FSs. Their ability to modulate gene expression at the transcriptional and post-transcriptional levels positions them as promising therapeutic targets. Research indicated that specific ncRNAs, such as miRNAs and lncRNAs, play significant roles in neuronal excitability and synaptic plasticity, which are critical in seizure activity. For instance, alterations in miRNA expression profiles have been found to be associated with increased seizure susceptibility, suggesting that targeting these ncRNAs could potentially mitigate seizure activity and improve clinical outcomes in patients with FSs (51,52), providing a basis for more personalized treatment approaches. The modulation of ncRNA expression through pharmacological agents or gene therapy provides a novel strategy for effectively managing FSs, especially in cases where conventional treatments are ineffective or lead to adverse effects (53,54). As summarized in Table 2, a promising strategy involves the inhibition of pro-epileptogenic miRNAs, such as miR-134 using antisense oligonucleotides encapsulated in lipid nanoparticles. This approach directly addresses the mechanism of neuronal hyperexcitability and has shown efficacy in preclinical seizure models. Similarly, the augmentation of miR-146a, a key inflammation checkpoint regulator, using mimic-loaded dendrimers, represents a strategy to enhance the brain’s innate anti-inflammatory response during a febrile episode, potentially preventing the initiation of seizures.

Current status and future prospects for clinical applications

The clinical application of ncRNA therapeutics in the management of FSs is still in its infancy, however, recent advancements indicate a promising future. Current research is centered on elucidating the specific roles of various ncRNAs in seizure mechanisms and identifying their potential as therapeutic agents. Preliminary studies have demonstrated that manipulating the expression levels of certain ncRNAs can influence seizure thresholds and neuronal survival, providing novel directions for targeted therapies (38,55). However, challenges remain, including the efficient delivery of ncRNA-based therapeutics to the CNS, and the need for robust clinical trials to assess efficacy and safety profiles. Future prospects involve the development of nanocarrier systems to enhance the delivery of ncRNA therapeutics, as well as the integration of ncRNA modulation with existing treatment regimens to optimize patient outcomes (56,57). As understanding of the ncRNA landscape in FSs deepens, these molecules are expected to be instrumental in developing treatment strategies, potentially revolutionizing the management of this prevalent pediatric condition.

Conclusions

In conclusion, the complex pathophysiology of pediatric FS involves numerous biological pathways where ncRNAs may play a potential regulatory role. Current evidence demonstrates that ncRNAs may act as dynamic regulators rather than passive elements, potentially influencing seizure susceptibility and severity. While these findings provide a foundation for exploring novel diagnostic and therapeutic approaches, several key research priorities deserve emphasis: (I) the need for mechanistic studies to establish causal relationships between specific ncRNAs and FS pathogenesis using appropriate experimental models; (II) clinical validation of proposed biomarker candidates with particular attention to specificity challenges in differentiating FS from other febrile conditions; and (III) addressing the translational hurdles in developing ncRNA-based therapeutics for pediatric populations. Future research should concentrate on bridging the gap between correlative findings and functional validation to advance this promising field.

Acknowledgments

We thank Medjaden Inc. for the scientific editing of this manuscript.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-15/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-15/prf

Funding: This work was supported by Scientific Research Project of the Traditional Chinese Medicine Bureau of Guangdong Province (No. 20251284).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-15/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Kaushik JS, Sondhi V, Yoganathan S, et al. Association of Child Neurology (AOCN) Consensus Statement on the Diagnosis and Management of Febrile Seizures. Indian Pediatr 2022;59:300-6.
2. Pokhrel RP, Bhurtel R, Malla KK, et al. Study of Febrile Seizure among Hospitalized Children of a Tertiary Centre of Nepal: A Descriptive Cross-sectional Study. JNMA J Nepal Med Assoc 2021;59:526-30. [Crossref] [PubMed]
3. Varnado S, Price D. Basics of modern epilepsy classification and terminology. Curr Probl Pediatr Adolesc Health Care 2020;50:100891. [Crossref] [PubMed]
4. Falsaperla R, Marino S, Vitaliti G, et al. Simple febrile seizures: new cut off for the duration of the crises. Acta Neurol Belg 2023;123:1339-44. [Crossref] [PubMed]
5. Kleeberger JA, Tomsits PJ, Kääb S, et al. Non-coding RNA and Cardiac Electrophysiological Disorders. Adv Exp Med Biol 2020;1229:301-10. [Crossref] [PubMed]
6. Nitsche A, Arnold C, Ueberham U, et al. Alzheimer-related genes show accelerated evolution. Mol Psychiatry 2021;26:5790-6. [Crossref] [PubMed]
7. Brück M, Berghoff BA, Schindler D. In Silico Design, In Vitro Construction, and In Vivo Application of Synthetic Small Regulatory RNAs in Bacteria. Methods Mol Biol 2024;2760:479-507. [Crossref] [PubMed]
8. Awan HM, Shah A, Rashid F, et al. Primate-specific Long Non-coding RNAs and MicroRNAs. Genomics Proteomics Bioinformatics 2017;15:187-95. [Crossref] [PubMed]
9. Tiwari D, Peariso K, Gross C. MicroRNA-induced silencing in epilepsy: Opportunities and challenges for clinical application. Dev Dyn 2018;247:94-110. [Crossref] [PubMed]
10. Farmanzadeh A, Qujeq D, Yousefi T. The Interaction Network of MicroRNAs with Cytokines and Signaling Pathways in Allergic Asthma. Microrna 2022;11:104-17. [Crossref] [PubMed]
11. Parsons E, Claud K, Petrof EO. The infant microbiome and implications for central nervous system development. Prog Mol Biol Transl Sci 2020;171:1-13. [Crossref] [PubMed]
12. Lago-Baldaia I, Fernandes VM, Ackerman SD. More Than Mortar: Glia as Architects of Nervous System Development and Disease. Front Cell Dev Biol 2020;8:611269. [Crossref] [PubMed]
13. Viljetić B, Blažetić S, Labak I, et al. Lipid Rafts: The Maestros of Normal Brain Development. Biomolecules 2024;14:362. [Crossref] [PubMed]
14. Semple BD, Dill LK, O'Brien TJ. Immune Challenges and Seizures: How Do Early Life Insults Influence Epileptogenesis? Front Pharmacol 2020;11:2. [Crossref] [PubMed]
15. Tan TH, Perucca P, O'Brien TJ, et al. Inflammation, ictogenesis, and epileptogenesis: An exploration through human disease. Epilepsia 2021;62:303-24. [Crossref] [PubMed]
16. Das S, Paramita P, Swain N, et al. Hospital-Based Prevalence, Electroencephalogram (EEG), and Neuroimaging Correlation in Seizures Among Children in Odisha, India. Cureus 2022;14:e21103. [Crossref] [PubMed]
17. Damiano JA, Deng L, Li W, et al. SCN1A Variants in vaccine-related febrile seizures: A prospective study. Ann Neurol 2020;87:281-8. [Crossref] [PubMed]
18. Kuruva UB, Kompally V, Bukkapatnam SB, et al. Etiological and risk factors in recurrent febrile seizures: Insights through EEG analysis. Qatar Med J 2023;2023:32. [Crossref] [PubMed]
19. Kumar N, Midha T, Rao YK. Risk Factors of Recurrence of Febrile Seizures in Children in a Tertiary Care Hospital in Kanpur: A One Year Follow Up Study. Ann Indian Acad Neurol 2019;22:31-6. [Crossref] [PubMed]
20. Shao L, Yu Y. Development of a prediction nomogram model of recurrent febrile seizures in pediatric children. Eur J Pediatr 2023;182:4875-88. [Crossref] [PubMed]
21. Smolander J, Stupnikov A, Glazko G, et al. Comparing biological information contained in mRNA and non-coding RNAs for classification of lung cancer patients. BMC Cancer 2019;19:1176. [Crossref] [PubMed]
22. Youssef SS, Elfiky A, Nabeel MM, et al. Assessment of circulating levels of microRNA-326, microRNA-424, and microRNA-511 as biomarkers for hepatocellular carcinoma in Egyptians. World J Hepatol 2022;14:1562-75. [Crossref] [PubMed]
23. Ghanbarian H, Yıldız MT, Tutar Y. MicroRNA Targeting. Methods Mol Biol 2022;2257:105-30. [Crossref] [PubMed]
24. Staněk D. Long non-coding RNAs and splicing. Essays Biochem 2021;65:723-9. [Crossref] [PubMed]
25. Yoshino Y, Dwivedi Y. Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior. Front Psychiatry 2020;11:543893. [Crossref] [PubMed]
26. He D, Zheng J, Hu J, et al. Long non-coding RNAs and pyroptosis. Clin Chim Acta 2020;504:201-8. [Crossref] [PubMed]
27. Li Q, Liu X, Wen J, et al. Enhancer RNAs: mechanisms in transcriptional regulation and functions in diseases. Cell Commun Signal 2023;21:191. [Crossref] [PubMed]
28. Kumar S, Gonzalez EA, Rameshwar P, et al. Non-Coding RNAs as Mediators of Epigenetic Changes in Malignancies. Cancers (Basel) 2020;12:3657. [Crossref] [PubMed]
29. Kabzinski J, Kucharska-Lusina A, Majsterek I. RNA-Based Liquid Biopsy in Head and Neck Cancer. Cells 2023;12:1916. [Crossref] [PubMed]
30. Jimenez-Mateos EM, Engel T, Merino-Serrais P, et al. Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nat Med 2012;18:1087-94. [Crossref] [PubMed]
31. Chen L, Dong R, Lu Y, et al. MicroRNA-146a protects against cognitive decline induced by surgical trauma by suppressing hippocampal neuroinflammation in mice. Brain Behav Immun 2019;78:188-201. [Crossref] [PubMed]
32. Li J, Sun C, Cui H, et al. Role of circRNAs in neurodevelopment and neurodegenerative diseases. J Mol Neurosci 2021;71:1743-51. [Crossref] [PubMed]
33. Sledziowska M, Winczura K, Jones M, et al. Non-coding RNAs associated with Prader-Willi syndrome regulate transcription of neurodevelopmental genes in human induced pluripotent stem cells. Hum Mol Genet 2023;32:608-20. [Crossref] [PubMed]
34. Schulte LN, Bertrams W, Stielow C, et al. ncRNAs in Inflammatory and Infectious Diseases. Methods Mol Biol 2019;1912:3-32. [Crossref] [PubMed]
35. Liu AR, Yan ZW, Jiang LY, et al. The role of non-coding RNA in the diagnosis and treatment of Helicobacter pylori-related gastric cancer, with a focus on inflammation and immune response. Front Med (Lausanne) 2022;9:1009021. [Crossref] [PubMed]
36. Dayal S, Chaubey D, Joshi DC, et al. Noncoding RNAs: Emerging regulators of behavioral complexity. Wiley Interdiscip Rev RNA 2024;15:e1847. [Crossref] [PubMed]
37. Gu Q, Liu H, Ma J, et al. A Narrative Review of Circular RNAs in Brain Development and Diseases of Preterm Infants. Front Pediatr 2021;9:706012. [Crossref] [PubMed]
38. Zhao C, Lv Y, Duan Y, et al. Circulating Non-coding RNAs and Cardiovascular Diseases. Adv Exp Med Biol 2020;1229:357-67. [Crossref] [PubMed]
39. Movahedpour A, Khatami SH, Karami N, et al. Exosomal noncoding RNAs in prostate cancer. Clin Chim Acta 2022;537:127-32. [Crossref] [PubMed]
40. Desideri F, D'Ambra E, Laneve P, et al. Advances in endogenous RNA pull-down: A straightforward dextran sulfate-based method enhancing RNA recovery. Front Mol Biosci 2022;9:1004746. [Crossref] [PubMed]
41. Loganathan TS, Sulaiman SA, Abdul Murad NA, et al. Interactions Among Non-Coding RNAs in Diabetic Nephropathy. Front Pharmacol 2020;11:191. [Crossref] [PubMed]
42. Butz H, Patócs A, Igaz P. Circulating non-coding RNA biomarkers of endocrine tumours. Nat Rev Endocrinol 2024;20:600-14. [Crossref] [PubMed]
43. Sarraf JS, Puty TC, da Silva EM, et al. Noncoding RNAs and Colorectal Cancer: A General Overview. Microrna 2020;9:336-45. [Crossref] [PubMed]
44. Rahimian N, Sheida A, Rajabi M, et al. Non-coding RNAs and exosomal non-coding RNAs in pituitary adenoma. Pathol Res Pract 2023;248:154649. [Crossref] [PubMed]
45. Roso-Mares A, Andújar I, Díaz Corpas T, et al. Non-coding RNAs as skin disease biomarkers, molecular signatures, and therapeutic targets. Hum Genet 2024;143:801-12. [Crossref] [PubMed]
46. Kalmatte A, Rekha PD, Ratnacaram CK. Emerging cell cycle related non-coding RNA biomarkers from saliva and blood for oral squamous cell carcinoma. Mol Biol Rep 2023;50:9479-96. [Crossref] [PubMed]
47. Tao M, Zheng M, Xu Y, et al. CircRNAs and their regulatory roles in cancers. Mol Med 2021;27:94. [Crossref] [PubMed]
48. Wang J, Fu G, Wang Q, et al. Differences of circular RNA expression profiles between monozygotic twins' blood, with the forensic application in bloodstain and saliva. Forensic Sci Int Genet 2024;69:103001. [Crossref] [PubMed]
49. Wang D, Ye R, Cai Z, et al. Emerging roles of RNA-RNA interactions in transcriptional regulation. Wiley Interdiscip Rev RNA 2022;13:e1712. [Crossref] [PubMed]
50. Gu J, Su C, Huang F, et al. Past, Present and Future: The Relationship Between Circular RNA and Immunity. Front Immunol 2022;13:894707. [Crossref] [PubMed]
51. Zhang Y, Xie J. Unveiling the role of ferroptosis-associated exosomal non-coding RNAs in cancer pathogenesis. Biomed Pharmacother 2024;172:116235. [Crossref] [PubMed]
52. Hueso M, Mallén A, Suñé-Pou M, et al. ncRNAs in Therapeutics: Challenges and Limitations in Nucleic Acid-Based Drug Delivery. Int J Mol Sci 2021;22:11596. [Crossref] [PubMed]
53. Break MKB, Syed RU, Hussein W, et al. Noncoding RNAs as therapeutic targets in autophagy-related diabetic cardiomyopathy. Pathol Res Pract 2024;256:155225. [Crossref] [PubMed]
54. Seyednejad SA, Sartor GC. Noncoding RNA therapeutics for substance use disorder. Adv Drug Alcohol Res 2022;2:10807. [Crossref] [PubMed]
55. Yang F, Ao X, Ding L, et al. Non-coding RNAs in Kawasaki disease: Molecular mechanisms and clinical implications. Bioessays 2022;44:e2100256. [Crossref] [PubMed]
56. Shao JL, Wang LJ, Xiao J, et al. Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury. World J Gastroenterol 2023;29:4927-41. [Crossref] [PubMed]
57. Sabet Sarvestani F, Afshari A, Azarpira N. The role of non-protein-coding RNAs in ischemic acute kidney injury. Front Immunol 2024;15:1230742. [Crossref] [PubMed]