Regulatory Roles Of Non-coding RNAs Research Articles

Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

Whole-transcriptome sequencing revealed the ceRNA regulatory network during the proliferation and differentiation of goose myoblast

The Shitou goose, the largest meat-type goose breed, is an ideal model for offering insights into enhancing meat production efficiency through understanding its genetic regulation of muscle development. Here, through whole-transcriptomic analysis of embryonic leg muscles, we identified 847 differentially expressed genes (DEG), 244 differentially expressed lncRNAs (DEL), 37 differentially expressed circRNAs (DEC), and 84 differentially expressed miRNAs (DEM). Gene ontology (GO) analysis highlighted the significant enrichment of differentially expressed RNAs in muscle structure development, actin filament-based processes, and the actin cytoskeleton pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified pathways associated with the FoxO signaling pathway, AMPK signaling pathway, Wnt signaling pathway and calcium signaling pathway. Furthermore, we utilized Miranda, TargetScan, and miRDB to identify regulatory networks that involve interactions between lncRNA-mRNA, circRNA-mRNA, miRNA-mRNA, lncRNA-miRNA-mRNA, and circRNA-miRNA-mRNA, which regulated the growth and development of skeletal muscle. Notably, differentially expressed genes within the ceRNA network were most significantly enriched in the regulation of actin cytoskeletal organization. Additionally, a lncRNA/circRNA-miRNA-mRNA ceRNA network related to muscle growth and development was constructed based on protein-protein interaction (PPI) analysis and hub genes selection using Cytoscape. This further elucidated the regulatory roles of noncoding RNAs (ncRNA) in the formation of muscle fibers in Shitou goose. In summary, this study provides a valuable transcriptional regulatory network for goose muscle development laying the groundwork for further exploration of the molecular regulatory mechanisms underlying the excellent meat production performance of Shitou goose.

Emerging roles of non-coding RNAs in fibroblast to myofibroblast transition and fibrotic diseases.

The transition of fibroblasts to myofibroblasts (FMT) represents a pivotal process in wound healing, tissue repair, and fibrotic diseases. This intricate transformation involves dynamic changes in cellular morphology, gene expression, and extracellular matrix remodeling. While extensively studied at the molecular level, recent research has illuminated the regulatory roles of non-coding RNAs (ncRNAs) in orchestrating FMT. This review explores the emerging roles of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating this intricate process. NcRNAs interface with key signaling pathways, transcription factors, and epigenetic mechanisms to fine-tune gene expression during FMT. Their functions are critical in maintaining tissue homeostasis, and disruptions in these regulatory networks have been linked to pathological fibrosis across various tissues. Understanding the dynamic roles of ncRNAs in FMT bears therapeutic promise. Targeting specific ncRNAs holds potential to mitigate exaggerated myofibroblast activation and tissue fibrosis. However, challenges in delivery and specificity of ncRNA-based therapies remain. In summary, ncRNAs emerge as integral regulators in the symphony of FMT, orchestrating the balance between quiescent fibroblasts and activated myofibroblasts. As research advances, these ncRNAs appear to be prospects for innovative therapeutic strategies, offering hope in taming the complexities of fibrosis and restoring tissue equilibrium.

Revealing the dynamic whole transcriptome landscape of Clonorchis sinensis: Insights into the regulatory roles of noncoding RNAs and microtubule-related genes in development.

Clonorchis sinensis is a significant zoonotic food-borne parasite that causes a range of hepatobiliary diseases, which in severe cases can even lead to cholangiocarcinoma. To explore new diagnostic and treatment strategies, the dynamic RNA regulatory processes across different developmental stages of C. sinensis were analyzed by using whole-transcriptome sequencing. The chromosomal-level genome of C. sinensis was used for sequence alignment and annotation. In this study, we identified a total of 59,103 RNAs in the whole genome, including 2,384 miRNAs, 25,459 mRNAs, 27,564 lncRNAs and 3,696 circRNAs. Differential expression analysis identified 6,556 differentially expressed mRNAs, 2,231 lncRNAs, 877 miRNAs and 20 circRNAs at different developmental stages. Functional enrichment analysis highlighted the critical role of microtubule-related biological processes in the growth and development of C. sinensis. And coexpression analysis revealed 97 lncRNAs and 85 circRNAs that were coexpressed with 42 differentially expressed mRNAs that associated with microtubules at different developmental stages of C. sinensis. The expression of the microtubule-related genes dynein light chain 2 (DLC2) and dynein light chain 4 (DLC4) increased with C. sinensis development, and DLC2/4 could be inhibited by albendazole. Finally, by constructing competing endogenous RNA (ceRNA) networks, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA regulatory relationships were constructed, and the ceRNA networks of MSTRG.14258.5-novel_miR_2287-newGene_28215 and MSTRG.14258.5-novel_miR_2216-CSKR_109340 were verified. This study suggests, through whole transcriptome sequencing, that the context of microtubule regulation may play an essential role in the development and growth of C. sinensis.

Non-coding RNAs in Precursor Lesions of Colorectal Cancer: Their Role in Cancer Initiation and Formation.

Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions.

Exploring the regulatory role of non-coding RNAs in fiber development and direct regulation of GhKCR2 in the fatty acid metabolic pathway in upland cotton

Cotton fiber holds immense importance as the primary raw material for the textile industry. Consequently, comprehending the regulatory mechanisms governing fiber development is pivotal for enhancing fiber quality. Our study aimed to construct a regulatory network of competing endogenous RNAs (ceRNAs) and assess the impact of non-coding RNAs on gene expression throughout fiber development. Through whole transcriptome data analysis, we identified differentially expressed genes (DEGs) regulated by non-coding RNA (ncRNA) that were predominantly enriched in phenylpropanoid biosynthesis and the fatty acid elongation pathway. This analysis involved two contrasting phenotypic materials (J02-508 and ZRI015) at five stages of fiber development. Additionally, we conducted a detailed analysis of genes involved in fatty acid elongation, including KCS, KCR, HACD, ECR, and ACOT, to unveil the factors contributing to the variation in fatty acid elongation between J02-508 and ZRI015. Through the integration of histochemical GUS staining, dual luciferase assay experiments, and correlation analysis of expression levels during fiber development stages for lncRNA MSTRG.44818.23 (MST23) and GhKCR2, we elucidated that MST23 positively regulates GhKCR2 expression in the fatty acid elongation pathway. This identification provides valuable insights into the molecular mechanisms underlying fiber development, emphasizing the intricate interplay between non-coding RNAs and protein-coding genes.

Role of regulatory non-coding RNAs in traumatic brain injury

Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates. The prompt and accurate diagnosis of TBI in clinical contexts, coupled with the implementation of effective therapeutic strategies, remains an arduous challenge. However, a deeper understanding of changes in gene expression and the underlying molecular regulatory processes may alleviate this pressing issue. In recent years, the study of regulatory non-coding RNAs (ncRNAs), a diverse class of RNA molecules with regulatory functions, has been a potential game changer in TBI research. Notably, the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs has revealed their potential as novel diagnostic biomarkers and therapeutic targets for TBI, owing to their ability to regulate the expression of numerous genes. In this review, we seek to provide a comprehensive overview of the functions of regulatory ncRNAs in TBI. We also summarize regulatory ncRNAs used for treatment in animal models, as well as miRNAs, lncRNAs, and circRNAs that served as biomarkers for TBI diagnosis and prognosis. Finally, we discuss future challenges and prospects in diagnosing and treating TBI patients in the clinical settings.

Regulation of cashmere fineness traits by noncoding RNA in Jiangnan cashmere goats

BackgroundCashmere has long been used as the raw material for wool textiles. The diameter of the cashmere fibre determines its quality and economic value. However, the regulatory role of noncoding RNAs (ncRNAs) in cashmere fineness remains unclear, especially regarding the interaction between ncRNAs and coding RNAs.ResultsTranscriptome sequencing was used to identify the expression profiles of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in the skin tissues of Jiangnan cashmere goats with different cashmere fineness levels. Integration analysis of ncRNA and coding RNA was performed in combination with previous research results. The results showed that 16,437 lncRNAs, 2234 circRNAs, and 1322 miRNAs were identified in 8 skin samples of cashmere goats. A total of 403 differentially expressed (DE) lncRNAs, 62 DE circRNAs and 30 DE miRNAs were identified in the skin tissues of the fine groups (Fe) and coarse groups (Ce). We predicted the target gene of DE lncRNA, the target gene of DE miRNA and the host gene of DE circRNA. Based on functional annotation and enrichment analysis of target genes, we found that DE lncRNAs could be involved in regulating the fineness traits of cashmere. The most potential lncRNAs were MSTRG.42054.1, MSTRG.18602.3, and MSTRG.2199.13.ConclusionsThe data from this study enriched the cashmere goat noncoding RNA database and helped to supplement the annotation of the goat genome. The results provided a new direction for the breeding of cashmere characters.

Cancer quiescence: non-coding RNAs in the spotlight.

Cancer quiescence reflects the ability of cancer cells to enter a reversible slow-cycling or mitotically dormant state and represents a powerful self-protecting mechanism preventing cancer cell 'damage' from hypoxic conditions, nutrient deprivation, immune surveillance, and (chemo)therapy. When stress conditions are restrained, and tumor microenvironment becomes beneficial, quiescent cancer cells re-enter cell cycle to facilitate tumor spread and cancer progression/metastasis. Recent studies have highlighted the dynamic role of regulatory non-coding RNAs (ncRNAs) in orchestrating cancer quiescence. The elucidation of regulatory ncRNA networks will shed light on the quiescence-proliferation equilibrium and, ultimately, pave the way for new treatment options. Herein, we have summarized the ever-growing role of ncRNAs upon cancer quiescence regulation and their impact on treatment resistance and modern cancer therapeutics.

Regulatory role of circular RNAs in oral squamous cell carcinoma.

OSCC is a genomically complicated disease and advancements in the modern era of molecular oncology have enabled researchers to portray near-to-complete resolution of signaling landscape. Over the last two decades, overwhelming proof-of-concept has established mechanistic regulatory role of non-coding RNAs in carcinogenesis, including OSCC. Circular RNAs demonstrate a burgeoning facet of oncology research and molecular biologists are only beginning to appreciate and recognize the significance of circRNAs in the pathogenesis of OSCC. Regulatory roles of non-coding RNAs in the re-shaping of signaling pathways offer plausible strategies for prevention/inhibition of OSCC. Circular RNAs have mechanistic roles in OSCC and "sponge effects" mediated by a wider variety of circRNAs need to be rationally targeted for effective cancer prevention. Phenomenal and cutting-edge research works in different types of animal models will further refine our knowledge for selection of most promising circRNAs as pharmacologically valuable targets.

Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models.

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the "ubiquitinome" is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.

PiRNA hsa_piR_019914 Promoted Chondrocyte Anabolic Metabolism By Inhibiting LDHA-Dependent ROS Production.

Osteoarthritis (OA) is the most common joint disease. The occurrence and progression of OA are regulated by epigenetics. A large number of studies have shown the important regulatory role of noncoding RNAs in joint diseases. As the largest class of noncoding small RNAs, the importance of piRNAs in many diseases, especially cancer, has been increasingly recognized. However, few studies have explored the role of piRNAs in OA. Our study showed that hsa_piR_019914 decreased significantly in OA. This study aimed to demonstrate the role of hsa_piR_019914 as a potential biological target of OA in chondrocytes. The GEO database and bioinformatics analysis were used for a series of screenings, and the OA model using human articular chondrocytes (C28/I2 cells), SW1353 cells under inflammatory factor stimulation was used to determine that hsa_piR_019914 was significantly downregulated in OA. Overexpression or inhibition of hsa_piR_019914 in C28/I2 cells was achieved by transfecting mimics or inhibitors. The effect of hsa_piR_019914 on the biological function of chondrocytes was verified by qPCR, flow cytometry, and colony formation assays in vitro. The target gene of hsa_piR_019914, lactate dehydrogenase A (LDHA), was screened by small RNA sequencing and quantitative polymerase chain reaction (qPCR), LDHA was knocked out in C28/I2 cells by the transfection of siRNA LDHA, and the relationship between hsa_piR_019914, LDHA, and reactive oxygen species (ROS) production was verified by flow cytometry. The piRNA hsa-piR-019914 was significantly downregulated in osteoarthritis (OA). Hsa-piR-019914 reduced inflammation-mediated chondrocyte apoptosis and maintained cell proliferation and clone formation in vitro. Hsa-piR-019914 reduced the production of LDHA-dependent ROS through targeted regulation of LDHA expression, maintained chondrocyte-specific gene expression of ACAN and COL2, and inhibited the gene expression of MMP3 and MMP13. Collectively, this study showed that hsa_piR_019914 was negatively correlated with the expression of LDHA, which mediates ROS production. Under the stimulation of inflammatory factors, overexpression of hsa_piR_019914 had a protective effect on chondrocytes in vitro, and the absence of hsa_piR_019914 exacerbated the negative effect of inflammation on chondrocytes. Studies on piRNAs provide new therapeutic interventions for OA.

Pyroptosis-related noncoding RNAs and cancer involvement

Abstract Cell pyroptosis, an inflammatory and programmed cell necrosis, is also an important cause of multiple organ damage and immunosuppression. Pyroptosis, a new kind of programmed cell death, leads to cleavage of the pyroptotic protein Gasdermin family and ultimately to membrane pore formation, cell shrinkage, plasma membrane cleavage, chromatin disruption and release of pro-inflammatory components. Various studies found that pyroptosis had a key role in cancer and inflammatory diseases. Gasdermin family is key protein in pyrotopsis. Non-coding RNAs have a potential role in cell pyrotosis which regulate immunity and cell death. This article reviews cell pyroptosis, GSDM family and the regulatory role of non-coding RNAs.

Non-Coding RNAs and Adipogenesis.

Adipogenesis is regarded as an intricate network in which multiple transcription factors and signal pathways are involved. Recently, big efforts have focused on understanding the epigenetic mechanisms and their involvement in the regulation of adipocyte development. Multiple studies investigating the regulatory role of non-coding RNAs (ncRNAs) in adipogenesis have been reported so far, especially lncRNA, miRNA, and circRNA. They regulate gene expression at multiple levels through interactions with proteins, DNA, and RNA. Exploring the mechanism of adipogenesis and developments in the field of non-coding RNA may provide a new insight to identify therapeutic targets for obesity and related diseases. Therefore, this article outlines the process of adipogenesis, and discusses updated roles and mechanisms of ncRNAs in the development of adipocytes.

Novel regulatory role of non-coding RNAs in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a type of arthritis that primarily affects the spine and involves disorders of the immune and skeletal systems. However, the exact pathogenesis of AS is not fully understood. Non-coding RNAs (ncRNAs), particularly, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs) and their interactions have been shown to influence many biological processes such as inflammatory responses, osteogenic differentiation and apoptosis, pyroptosis, and proliferation. In addition, ncRNAs reflect the disease activity of AS. In this review, we discuss the regulatory roles of ncRNAs in AS cell functions (inflammatory responses, cellular osteogenic differentiation and apoptosis, pyroptosis, and proliferation) and their potential applications in AS diagnosis and treatment. Understanding the role of ncRNAs in the pathogenesis of AS will lay the foundation for exploring potential new therapeutic approaches for AS.

Regulatory roles of noncoding RNAs in callus induction and plant cell dedifferentiation.

Plant regulatory noncoding RNAs (ncRNAs) have emerged as key modulators of gene expression during callus induction. Their further study may promote the design of innovative plant tissue culture protocols. The use of plants by humans has recently taken on a new and expanding insight due to the advent of genetic engineering technologies. In this context, callus cultures have shown remarkable potential for synthesizing valuable biomolecules, crop improvement, plant micropropagation, and biodiversity preservation. A crucial stage in callus production is the conversion of somatic cells into totipotent cells; compelling evidence indicates that stress factors, transcriptional regulators, and plant hormones can trigger this biological event. Besides, posttranscriptional regulators of gene expression might be essential participants in callus induction. However, research related to the analysis of noncoding RNAs (ncRNAs) that modulate callogenesis and plant cell dedifferentiation in vitro is still at an early stage. During the last decade, some relevant studies have enlightened the fact that different classes of ncRNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and long noncoding RNAs (lncRNAs) are implicated in plant cell dedifferentiation through regulating the expression levels of diverse gene targets. Hence, understanding the molecular relevance of these ncRNAs in the aforesaid biological processes might represent a promising source of new biotechnological approaches for callus culture and plant improvement. In this current work, we review the experimental evidence regarding the prospective roles of ncRNAs in callus induction and plant cell dedifferentiation to promote this field of study.

Regulatory roles of noncoding RNAs in intervertebral disc degeneration as potential therapeutic targets (Review).

Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, which is one of the primary factors that lead to disability and pose a serious economic burden. The key pathological processes involved are extracellular matrix degradation, autophagy, apoptosis, and inflammation of nucleus pulposus cells. Non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs and circular RNAs, are key regulators of the aforementioned processes. ncRNAs are differentially expressed in tissues of the intervertebral disc between healthy individuals and patients and participate in the pathological progression of IDD via a complex pattern of gene regulation. However, the regulatory mechanisms of ncRNAs in IDD remain unclear. The present review summarizes the latest insights into the regulatory role of ncRNAs in IDD and sheds light on potentially novel therapeutic strategies for IDD that may be implemented in the future.

The gene regulatory role of non-coding RNAs in non-obstructive azoospermia

Non-coding RNAs are classified as small non-coding RNAs, long non-coding RNAs and circular RNAs, which are involved in a variety of biological processes, including cell differentiation, proliferation, apoptosis and pathological conditions of various diseases. Many studies have shown that non-coding RNAs are related to spermatogenesis, maturation, apoptosis, function, etc. In addition, the expression of non-coding RNAs in testicular tissue and semen of patients with non-obstructive azoospermia was different. However, the role of non-coding RNAs in the pathogenesis of non-obstructive azoospermia has not been fully elucidated, and the role of non-coding RNAs in non-obstructive azoospermia is rarely reviewed. Here we summarize the research progress of non-coding RNAs in the pathogenesis of non-obstructive azoospermia.

Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities.

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.

Advances in the Immune Regulatory Role of Non-Coding RNAs (miRNAs and lncRNAs) in Insect-Pathogen Interactions.

Insects are by far the most abundant and diverse living organisms on earth and are frequently prone to microbial attacks. In other to counteract and overcome microbial invasions, insects have in an evolutionary way conserved and developed immune defense mechanisms such as Toll, immune deficiency (Imd), and JAK/STAT signaling pathways leading to the expression of antimicrobial peptides. These pathways have accessory immune effector mechanisms, such as phagocytosis, encapsulation, melanization, nodulation, RNA interference (RNAi), lysis, autophagy, and apoptosis. However, pathogens evolved strategies that circumvent host immune response following infections, which may have helped insects further sophisticate their immune response mechanisms. The involvement of ncRNAs in insect immunity is undeniable, and several excellent studies or reviews have investigated and described their roles in various insects. However, the functional analyses of ncRNAs in insects upon pathogen attacks are not exhaustive as novel ncRNAs are being increasingly discovered in those organisms. This article gives an overview of the main insect signaling pathways and effector mechanisms activated by pathogen invaders and summarizes the latest findings of the immune modulation role of both insect- and pathogen-encoded ncRNAs, especially miRNAs and lncRNAs during insect–pathogen crosstalk.