Class Of RNAs Research Articles

CircHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA

Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses. Expression-coupled motif analyses identify an 11-mer motif within circHIPK3, which also becomes enriched in genes that are downregulated upon circHIPK3 depletion. By mining eCLIP datasets and combined with RNA immunoprecipitation assays, we demonstrate that the 11-mer motif constitutes a strong binding site for IGF2BP2 in bladder cancer cell lines. Our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-STAT3 mRNA binding and, thereby, STAT3 mRNA levels. Surprisingly, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Our results support a model where a few cellular circHIPK3 molecules can induce IGF2BP2 condensation, thereby regulating key factors for cell proliferation.

CircHIPK3 nucleates IGF2BP2 and functions as a competing endogenous RNA.

Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses. Expression-coupled motif analyses identify an 11-mer motif within circHIPK3, which also becomes enriched in genes that are downregulated upon circHIPK3 depletion. By mining eCLIP datasets and combined with RNA immunoprecipitation assays, we demonstrate that the 11-mer motif constitutes a strong binding site for IGF2BP2 in bladder cancer cell lines. Our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-STAT3 mRNA binding and, thereby, STAT3 mRNA levels. Surprisingly, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Our results support a model where a few cellular circHIPK3 molecules can induce IGF2BP2 condensation, thereby regulating key factors for cell proliferation.

MicroRNA-26a deficiency attenuates the severity of frozen shoulder in a mouse immobilization model.

The main pathogenesis of the frozen shoulder is thought to be the inflammation of the intra-articular synovium and subsequent fibrosis of the shoulder joint capsule. However, the molecular pathogenesis of the frozen shoulder is still unknown. A class of noncoding RNAs, microRNAs contribute to various diseases including musculoskeletal diseases. MicroRNA-26a (miR-26a) has been reported to be associated with fibrosis in several organs. This study aims to reveal the role of miR-26a on fibrosis in the shoulder capsule using a frozen shoulder model in miR-26a deficient (miR-26a KO) mice. MiR-26a KO and wild-type (WT) mice were investigated using a frozen shoulder model. The range of motion (ROM) of the shoulder, histopathological changes such as synovitis, and fibrosis-related gene expression in the model mice were evaluated to determine the role of miR-26a. In WT mice, both inflammatory cell infiltration and thickening of the inferior shoulder joint capsule were observed after 1 week of immobilization, and this thickening further progressed over the subsequent 6 weeks. However, the immobilized shoulder in miR-26a KO mice consistently exhibited significantly better ROM compared with WT mice at 1 and 6 weeks, and histological changes were significantly less severe. The expression of inflammation- and fibrosis-related genes was decreased in the miR-26a KO mice compared with WT mice at 1 and 6 weeks. Together, miR-26a deficiency attenuated the severity of frozen shoulder in the immobilization model mouse. The present study suggests that miR-26a has the potential to be a target miRNA for therapeutic approach to frozen shoulder.

Identification and functional analysis of circular RNA expression profiles associated with ammonia exposure in chicken lungs

Ammonia acts as a detrimental atmospheric pollutant, posing a sever threat to respiratory tract health and causing lung injury in humans and animals. Circular RNAs (circRNAs) are a distinctive class of non-coding RNA generated by back-splicing of linear RNA, implicated in various biological processes. However, their role in the immune response of chicken lungs to ammonia exposure remains unclear. In this study, we examined the expression profiles of circRNAs in chicken lungs under ammonia stimulation. In total, 61 differentially expressed (DE) circRNAs were identified between the ammonia exposure and control groups, including 17 up-regulated and 44 down-regulated circRNAs. The source genes of these DE circRNAs were predominantly enriched in Influenza A, SNARE interactions in vesicular transport, and Notch signaling pathway. Notably, nine DE circRNAs (circNBAS, circMTIF2, circXPO1, circSNX24, circRAB11A, circARID3B, circUSP54, circPPARA, and circERG) were selected for validation the reliability and authenticity of RNA-seq data. Results showed the back-splicing circular structure, as well as the reliability and accuracy of RNA-seq data in quantifying circRNA expression, as the RT-qPCR results were in agreement with the RNA-seq data. Moreover, we constructed the circRNA-miRNA-mRNA regulatory networks and identified several regulatory networks in chicken lungs under ammonia stimulation, including circRAB11A-gga-miR-191b-3p-BRD2 and circARID3B-gga-miR-1696-CKS2. Taken together, our study delineates the circRNA expression profile and their potential roles in the immune response of chicken lungs to ammonia exposure. These findings offer insights into molecular mechanisms that may mitigate diseases associated with ammonia induced respiratory tract pollution in humans and animals.

Systematic assessment of serum i-tRF-AsnGTT in gastric cancer: a potential clinical biomarker.

Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.

Roles and mechanisms of circular RNA in respiratory system cancers.

Circular RNAs (circRNAs) constitute a class of endogenous non-coding RNAs (ncRNAs) that lack a 5'-ended cap and 3'-ended poly (A) tail and form a closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant to Exonuclease R (RNaseR), making its distribution in the cytoplasm quite rich. Advanced high-throughput sequencing and bioinformatics methods have revealed that circRNA is highly conserved, stable, and disease- and tissue-specific. Furthermore, increasing research has confirmed that circRNA, as a driver or suppressor, regulates cancer onset and progression by modulating a series of pathophysiological mechanisms. As a result, circRNA has emerged as a clinical biomarker and therapeutic intervention target. This article reviews the biological functions and regulatory mechanisms of circRNA in the context of respiratory cancer onset and progression.

Novel Long Noncoding RNA HEAT4 Affects Monocyte Subtypes, Reducing Inflammation and Promoting Vascular Healing.

Activation of the immune system contributes to cardiovascular diseases. The role of human-specific long noncoding RNAs in cardioimmunology is poorly understood. Single-cell sequencing in peripheral blood mononuclear cells revealed a novel human-specific long noncoding RNA called HEAT4 (heart failure-associated transcript 4). HEAT4 expression was assessed in several in vitro and ex vivo models of immune cell activation, as well as in the blood of patients with heart failure (HF), acute myocardial infarction, or cardiogenic shock. The transcriptional regulation of HEAT4 was verified through cytokine treatment and single-cell sequencing. Loss-of-function and gain-of-function studies and multiple RNA-protein interaction assays uncovered a mechanistic role of HEAT4 in the monocyte anti-inflammatory gene program. HEAT4 expression and function was characterized in a vascular injury model in NOD.CB17-Prkdc scid/Rj mice. HEAT4 expression was increased in the blood of patients with HF, acute myocardial infarction, or cardiogenic shock. HEAT4 levels distinguished patients with HF from people without HF and predicted all-cause mortality in a cohort of patients with HF over 7 years of follow-up. Monocytes, particularly anti-inflammatory CD16+ monocytes, which are increased in patients with HF, are the primary source of HEAT4 expression in the blood. HEAT4 is transcriptionally activated by treatment with anti-inflammatory interleukin-10. HEAT4 activates anti-inflammatory and inhibits proinflammatory gene expression. Increased HEAT4 levels result in a shift toward more CD16+ monocytes. HEAT4 binds to S100A9, causing a monocyte subtype switch, thereby reducing inflammation. As a result, HEAT4 improves endothelial barrier integrity during inflammation and promotes vascular healing after injury in mice. These results characterize a novel endogenous anti-inflammatory pathway that involves the conversion of monocyte subtypes into anti-inflammatory CD16+ monocytes. The data identify a novel function for the class of long noncoding RNAs by preventing protein secretion and suggest long noncoding RNAs as potential targets for interventions in the field of cardioimmunology.

The roles of circular RNAs in nerve injury and repair.

Nerve injuries significantly impact the quality of life for patients, with severe cases posing life-threatening risks. A comprehensive understanding of the pathophysiological mechanisms underlying nerve injury is crucial to the development of effective strategies to promote nerve regeneration. Circular RNAs (circRNAs), a recently characterized class of RNAs distinguished by their covalently closed-loop structures, have been shown to play an important role in various biological processes. Numerous studies have highlighted the pivotal role of circRNAs in nerve regeneration, identifying them as potential therapeutic targets. This review aims to succinctly outline the latest advances in the role of circRNAs related to nerve injury repair and the underlying mechanisms, including peripheral nerve injury, traumatic brain injury, spinal cord injury, and neuropathic pain. Finally, we discuss the potential applications of circRNAs in drug development and consider the potential directions for future research in this field to provide insights into circRNAs in nerve injury repair.

Spherical nucleic acid nanoprobes for in situ and multiplex detection of exosomal PIWI-interacting RNAs

PIWI-interacting RNAs (piRNAs) are a novel class of non-coding RNAs that bind specifically to the PIWI subfamily of Argonaut proteins. It has been increasingly demonstrated that piRNAs encased in circulating exosomes could be an ample source of potential tumor markers for cancer diagnostics. However, methods on exosomal piRNAs detections are limited, and most of them need extraction of piRNAs from the sample which is laborious and disadvantage to clinical applications. Herein, we developed two kinds of dual-targeted spherical nucleic acid nanoprobes for in situ and multiplex detection of exosomal piRNAs. The detection scheme was rationally designed for the large sized targets of PIWI-interacting RNA complex which could generate steric hindrance in the detection reaction. The probes were synthesized by modifying 13-nm gold particles with high-density double stranded anchor-report DNA through butanol dehydration method. The key synthesis condition of molar ratio between the two kinds of anchor-report DNA chains were optimized for preparing probes with good structural reproducibility. The probes can perform in situ and multiplex detection of piRNAs in exosomes after simple incubation. In the clinical assays of plasma from breast cancer patients and normal control groups, the probes can differentiate the expression levels of 3 types of piRNAs and their combinations in high specificity and sensitivity. These new piRNA probes are potentially to perform simple and accurate liquid biopsy for cancer diagnostics.

The Role of microRNA in Schizophrenia: A Scoping Review.

Schizophrenia is a serious mental disease that is regulated by multiple genes and influenced by multiple factors. Due to the complexity of its etiology, the pathogenesis is still unclear. MicroRNAs belong to a class of small non-coding RNAs that are highly conserved in endogenous evolution and play critical roles in multiple biological pathways. In recent years, aberrant miRNA expression has been implicated in schizophrenia, with certain miRNAs emerging as potential diagnostic and prognostic biomarkers for this disorder. In this review, our objective is to investigate the differential expression of miRNAs in schizophrenia, elucidate their potential mechanisms of action, and assess their feasibility as biomarkers. The PubMed electronic database and Google Scholar were searched for the years 2003 to 2024. The study focused on schizophrenia and miRNA as the research topic, encompassing articles related to biomarkers, etiology, action mechanisms, and differentially expressed genes associated with schizophrenia and miRNA. A total of 1488 articles were retrieved, out of which 49 were included in this scope review. This study reviewed 49 articles and identified abnormal expression of miRNA in different tissues of both schizophrenia patients and healthy controls, suggesting its potential role in the pathogenesis and progression of schizophrenia. Notably, several specific miRNAs, including miR-34a, miR-130b, miR-193-3p, miR-675-3p, miR-1262, and miR-218-5p, may serve as promising biological markers for diagnosing schizophrenia. Furthermore, this study summarized potential mechanisms through which miRNAs may contribute to the development of schizophrenia. The studies within the field of miRNA's role in schizophrenia encompass a broad spectrum of focus. Several selected studies have identified dysregulated miRNAs associated with schizophrenia across various tissues, thereby highlighting the potential utility of specific miRNAs as diagnostic biomarkers for this disorder. Various mechanisms underlying dysregulated miRNAs in schizophrenia have been explored; however, further investigations are needed to determine the exact mechanisms by which these dysregulated miRNAs contribute to the pathogenesis of this condition. The exploration of miRNA's involvement in the etiology and identification of biomarkers for schizophrenia holds significant promise in informing future clinical trials and advancing our understanding in this area.

Direct testing of natural twister ribozymes from over a thousand organisms reveals a broad tolerance for structural imperfections.

ABSTRACTTwister ribozymes are an extensively studied class of nucleolytic RNAs. Thousands of natural twisters have been proposed using sequence homology and structural descriptors. Yet, most of these candidates have not been validated experimentally. To address this gap, we developed CHiTA (Cleavage High-Throughput Assay), a high-throughput pipeline utilizing massively parallel oligonucleotide synthesis and next-generation sequencing to test putative ribozymesen massein a scarless fashion. As proof of principle, we applied CHiTA to a small set of known active and mutant ribozymes. We then used CHiTA to test two large sets of naturally occurring twister ribozymes: over 1, 600 previously reported putative twisters and ∼1, 000 new candidate twisters. The new candidates were identified computationally in ∼1, 000 organisms, representing a massive increase in the number of ribozyme-harboring organisms. Approximately 94% of the twisters we tested were active and cleaved site-specifically. Analysis of their structural features revealed that many substitutions and helical imperfections can be tolerated. We repeated our computational search with structural descriptors updated from this analysis, whereupon we identified and confirmed the first intrinsically active twister ribozyme in mammals. CHiTA broadly expands the number of active twister ribozymes found in nature and provides a powerful method for functional analyses of other RNAs.GRAPHICAL ABSTRACT

Germ granule compartments coordinate specialized small RNA production

Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C. elegans germ granule is compartmentalized into multiple subcompartments whose biological functions are largely unknown. Here, we identify an uncharted subcompartment of the C. elegans germ granule, which we term the E granule. The E granule is nonrandomly positioned within the germ granule. We identify five proteins that localize to the E granule, including the RNA-dependent RNA polymerase (RdRP) EGO-1, the Dicer-related helicase DRH-3, the Tudor domain-containing protein EKL-1, and two intrinsically disordered proteins, EGC-1 and ELLI-1. Localization of EGO-1 to the E granule enables synthesis of a specialized class of 22G RNAs, which derive exclusively from 5’ regions of a subset of germline-expressed mRNAs. Defects in E granule assembly elicit disordered production of endogenous siRNAs, which disturbs fertility and the RNAi response. Our results define a distinct subcompartment of the C. elegans germ granule and suggest that one function of germ granule compartmentalization is to facilitate the localized production of specialized classes of small regulatory RNAs.

Unraveling the modulatory manner and function of circRNAs in the Asian honey bee larval guts.

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that can participate in biological processes such as gene expression, growth, and development. However, little has been explored about the function of circRNAs in the development of Apis cerana larval guts. By using our previously gained deep sequencing data from the guts of A. cerana worker larvae at 4-, 5-, and 6-day-old (Ac4, Ac5, and Ac6 groups), the expression pattern and regulatory role of circular RNAs (circRNAs) during the development process was comprehensively investigated, with a focus on differentially expressed circRNAs (DEcircRNAs) relevant to immunity pathways and developmental signaling pathways, followed by validation of the binding relationships among a key competing endogenous RNA (ceRNA) axis. Here, 224 (158) DEcircRNAs were detected in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group. It's suggested that 172 (123) parental genes of DEcircRNAs were involved in 26 (20) GO terms such as developmental process and metabolic process and 138 (136) KEGG pathways like Hippo and Wnt signaling pathways. Additionally, ceRNA network analysis indicated that 21 (11) DEcircRNAs could target seven (three) DEmiRNAs, further targeting 324 (198) DEmRNAs. These DEmRNAs can be annotated to 33 (26) GO terms and 168 (200) KEGG pathways, including 12 (16) cellular and humoral immune pathways (endocytosis, lysosome, Jak-STAT, etc.) and 10 (nine) developmental signaling pathways (Hippo, mTOR, Hedgehog, etc.). Interestingly, DEcircRNAs in these two comparison groups could target the same ace-miR-6001-y, forming complex sub-networks. The results of PCR and Sanger sequencing confirmed the back-splicing sites within four randomly selected DEcircRNAs. RT-qPCR detection of these four DEcircRNAs verified the reliability of the used transcriptome data. The results of dual-luciferase reporter assay verified the binding relationships between novel_circ_001627 and ace-miR-6001-y and between ace-miR-6001-y and apterous-like. Our data demonstrated that DEcircRNAs were likely to modulate the developmental process of the A. cerana worker larval guts via regulation of parental gene transcription and ceRNA network, and novel_circ_001627/ace-miR-6001-y/apterous-like was a potential regulatory axis in the larval gut development. Findings from this work offer a basis and a candidate ceRNA axis for illustrating the circRNA-modulated mechanisms underlying the A. cerana larval guts.

Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome.

Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.

An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases.

Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5' single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4+ T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type-specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type-resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.

TRNA-derived fragments in T lymphocyte-beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice.

tRNAs play a central role in protein synthesis. Besides this canonical function, they were recently found to generate non-coding RNA fragments (tRFs) regulating different cellular activities. The aim of this study was to assess the involvement of tRFs in the crosstalk between immune cells and beta cells and to investigate their contribution to the development of type 1 diabetes. Global profiling of the tRFs present in pancreatic islets of 4- and 8-week-old NOD mice and in extracellular vesicles released by activated CD4+ T lymphocytes was performed by small RNA-seq. Changes in the level of specific fragments were confirmed by quantitative PCR. The transfer of tRFs from immune cells to beta cells occurring during insulitis was assessed using an RNA-tagging approach. The functional role of tRFs increasing in beta cells during the initial phases of type 1 diabetes was determined by overexpressing them in dissociated islet cells and by determining the impact on gene expression and beta cell apoptosis. We found that the tRF pool was altered in the islets of NOD mice during the initial phases of type 1 diabetes. Part of these changes were triggered by prolonged exposure of beta cells to proinflammatory cytokines (IL-1β, TNF-α and IFN-γ) while others resulted from the delivery of tRFs produced by CD4+ T lymphocytes infiltrating the islets. Indeed, we identified several tRFs that were enriched in extracellular vesicles from CD4+/CD25- T cells and were transferred to beta cells upon adoptive transfer of these immune cells in NOD.SCID mice. The tRFs delivered to beta cells during the autoimmune reaction triggered gene expression changes that affected the immune regulatory capacity of insulin-secreting cells and rendered the cells more prone to apoptosis. Our data point to tRFs as novel players in the crosstalk between the immune system and insulin-secreting cells and suggest a potential involvement of this novel class of non-coding RNAs in type 1 diabetes pathogenesis. Sequences are available from the Gene Expression Omnibus (GEO) with accession numbers GSE242568 and GSE256343.

Exploring the role of microRNAs as diagnostic and prognostic biomarkers in canine mammary tumors.

Canine mammary tumors (CMTs) represent a significant health concern in dogs, with a high incidence among intact female dogs. CMTs are a promising comparative model for human breast cancer, due to sharing several pathophysiological features. Additionally, CMTs have a strong genetic correlation with their human counterpart, including the expression of microRNAs (miRNAs). MiRNAs are a class of non-coding RNAs that play important roles in post-translational regulation of gene expression, being implicated in carcinogenesis, tumor progression, and metastasis. Moreover, miRNAs hold promise as diagnostic, prognostic, and metastatic biomarkers. Understanding the molecular mechanisms underlying CMTs is crucial for improving diagnosis, prognosis, and monitoring of treatments. Herein, we provide a comprehensive overview of the current knowledge on miRNAs in CMTs, highlighting their roles in carcinogenesis and their potential as biomarkers. Additionally, we highlight the current limitations and critically discuss the overarching challenges in this field, emphasizing the need for future research to translate miRNA findings into veterinary clinical practice.

Exosomal microRNAs in lung cancer: a narrative review.

Exosomes are nanoscale extracellular vesicles secreted by cells, which can release bioactive macromolecules, such as microRNA (miRNA) to receptor cells. Exosomes can efficiently penetrate various biological barriers which mediate intercellular communication. MiRNA are a class of non-coding RNA that primarily regulate messenger RNA (mRNA) at the post-transcriptional level. MiRNA is abundant in exosomes, which plays an important role by being transported and released through exosomes secreted by lung cancer cells. This review aims to elucidate the roles of exosome-derived miRNAs in lung cancer. We focused on the roles of exosome-derived miRNAs in cancer occurrence and development, including angiogenesis, cell proliferation, invasion, metastasis, immune escape, drug resistance, and their clinical value as new diagnostic and prognostic markers for lung cancer. Exosomal miRNA can not only affect angiogenesis of lung cancer, induce epithelial-mesenchymal transformation, and promote reprogramming of tumor microenvironment, but also affect immune regulation and drug resistance transmission and participate in regulating lung cancer cell proliferation. Therefore, understanding the regulatory roles of exosomal miRNAs in tumor invasion and metastasis can provide new ideas for the treatment of lung cancer. Exosomal miRNA can provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future. Targeting tumor-specific exosomal miRNA represents a new strategy for clinical treatment of lung cancer, which can provide potential non-invasive biomarkers in the early diagnosis of lung cancer. Investigation of the involvement of exosomal miRNAs in the occurrence and progression of tumors can yield new opportunities for the clinical diagnosis and treatment of lung cancer.

SNORA28 Promotes Proliferation and Radioresistance in Colorectal Cancer Cells through the STAT3 Pathway by Increasing H3K9 Acetylation in the LIFR Promoter.

Radiotherapy is essential for treating colorectal cancer (CRC), especially in advanced rectal cancer. However, the low radiosensitivity of CRC cells greatly limits radiotherapy efficacy. Small nucleolar RNAs (snoRNAs) are a class of noncoding RNA that primarily direct post-transcriptional modifications of ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and other cellular RNAs. While snoRNAs are involved in tumor progression and chemoresistance, their association with radiosensitivity remains largely unknown. Herein, SNORA28 is shown highly expressed in CRC and is positively associated with poor prognosis. Furthermore, SNORA28 overexpression enhances the growth and radioresistance of CRC cells in vitro and in vivo. Mechanistically, SNORA28 acts as a molecular decoy that recruits bromodomain-containing protein 4 (BRD4), which increases the level of H3K9 acetylation at the LIFR promoter region. This stimulates LIFR transcription, which in turn triggers the JAK1/STAT3 pathway, enhancing the proliferation and radioresistance of CRC cells. Overall, these results highlight the ability of snoRNAs to regulate radiosensitivity in tumor cells and affect histone acetylation modification in the promoter region of target genes, thus broadening the current knowledge of snoRNA biological functions and the mechanism underlying target gene regulation.

The emerging roles of circHECTD1 in human diseases and the specific underlying regulatory mechanisms

Circular RNAs (circRNAs) are a class of single-stranded closed-loop RNAs that have become a popular research subject in biology. Compared to linear RNAs, they are more stable, more conserved, and more widely distributed, and they play crucial biological functions in many diseases. CircHECTD1, a newly identified member of the circRNA family, is widely distributed in humans. Recent studies have shown that circHECTD1 is abnormally expressed in various human diseases, including glioma, hepatocellular carcinoma, gastric cancer, acute ischaemic stroke, silicosis, acute lung injury, ulcerative colitis, atherosclerosis, and hypertrophic scarring. In malignant tumours, circHECTD1 is thought to be an oncogene that promotes malignant tumour behaviours and influences tumour prognosis. In nontumour diseases, it plays a dual role, promoting disease in silicosis, stroke, and other diseases, while alleviating the disease process in ulcerative colitis, acute lung injury, and atherosclerosis. This article provides a review of the regulatory roles and mechanisms of action of circHECTD1 in different diseases. We also discuss and prospectively evaluate the clinical potential of circHECTD1 as a diagnostic biomarker and a therapeutic target for related diseases, providing new insights for developing new therapeutic strategies.