Circular RNAs in laryngeal cancer.

Laryngeal cancer remains a significant global health concern, with poor prognosis for advanced-stage disease highlighting the need for novel diagnostic, prognostic, and therapeutic approaches. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, have emerged as important regulators of gene expression and cellular processes in various cancers, including laryngeal cancer. This review summarizes the current understanding of circRNAs in laryngeal cancer, covering their biogenesis, regulatory mechanisms, and potential clinical applications. We explore the diverse functions of circRNAs, including their roles as miRNA sponges, protein interactors, and direct mRNA regulators, and their influence on key cellular processes such as proliferation, invasion, and metastasis. The review highlights promising circRNAs as diagnostic and prognostic biomarkers, as well as potential therapeutic targets. We also outline current strategies for circRNA modulation, including suppression techniques like RNA interference and CRISPR/Cas systems, and overexpression methods using vectors and synthetic circRNAs.

Emerging roles of CircRNA-miRNA networks in cancer development and therapeutic response.

The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.

Comparative transcriptome of normal and cancer-associated fibroblasts.

BACKGROUND: The characteristics of a tumor are largely determined by its interaction with the surrounding micro-environment (TME). TME consists of both cellular and non-cellular components. Cancer-associated fibroblasts (CAFs) are a major component of the TME. They are a source of many secreted factors that influence the survival and progression of tumors as well as their response to drugs. Identification of markers either overexpressed in CAFs or unique to CAFs would pave the way for novel therapeutic strategies that in combination with conventional chemotherapy are likely to have better patient outcome. METHODS: Fibroblasts have been derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer. RNA from these has been used to perform a transcriptome analysis in order to get a comparative profile of normal and cancer-associated fibroblasts. RESULTS: The study has identified 818 differentially expressed mRNAs and 17 lincRNAs between normal and cancer-associated fibroblasts. Also, 15 potential lincRNA-miRNA-mRNA combinations have been identified which may be potential biomarkers. CONCLUSIONS: This study identified differentially expressed markers between normal and cancer-associated fibroblasts that would help in targeted therapy against CAFs/derived factors, in combination with conventional therapy. However, this would in future need more experimental validation.

Potential therapies for non-coding RNAs in breast cancer.

Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer.

Representation of non-coding RNA-mediated regulation of gene expression using the Gene Ontology.

Regulatory non-coding RNAs (ncRNAs) are increasingly recognized as integral to the control of biological processes. This is often through the targeted regulation of mRNA expression, but this is by no means the only mechanism through which regulatory ncRNAs act. The Gene Ontology (GO) has long been used for the systematic annotation of protein-coding and ncRNA gene function, but rapid progress in the understanding of ncRNAs meant that the ontology needed to be revised to accurately reflect current knowledge. Here, a targeted effort to revise GO terms used for the annotation of regulatory ncRNAs is described, focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). This paper provides guidance to biocurators annotating ncRNA-mediated processes using the GO and serves as background for researchers wishing to make use of the GO in their studies of ncRNAs and the biological processes they regulate.

Advancing prognostic understanding in hepatocellular carcinoma through the integration of genomic instability and lncRNA signatures: GILncSig model.

The recently published study by Duan et al introduces a promising method that combines genomic instability and long non-coding RNAs to improve the prognostic evaluation of hepatocellular carcinoma (HCC), a deadly cancer associated with considerable morbidity and mortality. This editorial aims to analyze the methodology, key findings, and broader implications of the study within the fields of gastroenterology and oncological surgery, highlighting the shift towards precision medicine in the management of HCC.

Circular RNA expression in turkey skeletal muscle satellite cells is significantly altered by thermal challenge.

Introduction: Understanding the genetic mechanisms behind muscle growth and development is crucial for improving the efficiency of animal protein production. Recent poultry studies have identified genes related to muscle development and explored how environmental stressors, such as temperature extremes, affect protein production and meat quality. Non-coding RNAs, including circular RNAs (circRNAs), play crucial roles in modulating gene expression and regulating the translation of mRNAs into proteins. This study examined circRNA expression in turkey skeletal muscle stem cells under thermal stress. The objectives were to identify and quantify circRNAs, assess circRNA abundance following RNAse R depletion, identify differentially expressed circRNAs (DECs), and predict potential microRNA (miRNA) targets for DECs and their associated genes. Materials and methods: Cultured cells from two genetic lines (Nicholas commercial turkey and The Ohio State Random Bred Control 2) under three thermal treatments: cold (33°C), control (38°C), and hot (43°C) were compared at both the proliferation and differentiation stages. CircRNA prediction and differential expression and splicing analyses were conducted using the CIRIquant pipeline for both the untreated and RNase R depletion treated libraries. Predicted interactions between DECs and miRNAs, as well as the potential impact of circRNA secondary structure on these interactions, were investigated. Results: A total of 11,125 circRNAs were predicted within the treatment groups, between both untreated and RNase R treated libraries. Differential expression analyses indicated that circRNA expression was significantly altered by thermal treatments and the genetic background of the stem cells. A total of 140 DECs were identified across the treatment comparisons. In general, more DECs within temperature treatment comparisons were identified in the proliferation stage and more DECs within genetic line comparisons were identified in the differentiation stage. Discussion: This study highlights the significant impact of environmental stressors on non-coding RNAs and their role in gene regulation. Elucidating the role of non-coding RNAs in gene regulation can help further our understanding of muscle development and poultry production, underscoring the broader implications of this research for enhancing animal protein production efficiency.

RNA in axons, dendrites, synapses and beyond.

In neurons, a diverse range of coding and non-coding RNAs localize to axons, dendrites, and synapses, where they facilitate rapid responses to local needs, such as axon and dendrite extension and branching, synapse formation, and synaptic plasticity. Here, we review the extent of our current understanding of RNA subclass diversity in these functionally demanding subcellular compartments. We discuss the similarities and differences identified between axonal, dendritic and synaptic local transcriptomes, and discuss the reported and hypothesized fates and functions of localized RNAs. Furthermore, we outline the RNA composition of exosomes that bud off from neurites, and their implications for the biology of neighboring cells. Finally, we highlight recent advances in third-generation sequencing technologies that will likely provide transformative insights into splice isoform and RNA modification diversity in local transcriptomes.

Genome-wide profiling of long non-coding RNA following ozone exposure: a randomized, controlled exposure trial.

BACKGROUND: Exposure to ambient ozone has been associated with extrapulmonary health, but the underlying mechanisms remain to be understood. LncRNAs are involved in the regulation of gene expression, but their regulatory mechanisms in ozone-related health effects are scarcely explored. OBJECTIVE: To investigate genome-wide lncRNA changes after short-term ozone exposure and their regulatory roles in ozone exposure and gene expression. METHOD: We conducted a randomized, crossover, controlled exposure trial in 32 healthy college students in Shanghai, China. Each participant received both 200-ppb ozone exposure and filtered air exposure for two hours in a random order with a 14-day washout period. Blood samples were collected after each exposure and used for lncRNA sequencing. Differentially expressed lncRNAs between the two exposures were identified using orthogonal partial least squares discriminant analysis and linear regression analysis. LncRNAs-targeted mRNAs were mapped and subjected to enrichment analyses. We also constructed lncRNA-miRNA-mRNA networks. RESULTS: A total of 90 lncRNAs were differentially expressed after exposure to ozone, with 49 up-regulated and 41 down-regulated. Enrichment analyses suggested that these dysregulated lncRNAs were involved in a variety of biological processes, including those related to oxidative stress, inflammation response, and cell proliferation, development, and differentiation. Multiple pathways such as IL-17 signaling, NF-kB signaling, and Rho GTPases signaling were also enriched. Furthermore, the lncRNA-miRNA-mRNA network revealed that specific lncRNAs may regulate the expression of inflammation- and angiogenesis-related genes by interacting with miRNAs, such as NEAT1/hsa-miR-500a-3p/SIGLEC8, NEAT1/hsa-miR-6835-3p/SLC16A14, OIP5-AS1/miR-183-5p/EGR1, and SNHG25/hsa-miR-663a/FOSB axes. CONCLUSION: This study characterized a thorough profile of human lncRNAs following short-term ozone exposure and suggested the regulatory roles of these lncRNAs in ozone-induced inflammatory responses and angiogenesis, providing novel epigenetic insights into the mechanisms of the health effects of ozone exposure.

Variation within the non-coding genome influences genetic and epigenetic regulation of the human leukocyte antigen genes.

Variation within the non-coding genome may influence the regulation and expression of important genes involved in immune control such as the human leukocyte antigen (HLA) system. Class I and Class II HLA molecules are essential for peptide presentation which is required for T lymphocyte activation. Single nucleotide polymorphisms within non-coding regions of HLA Class I and Class II genes may influence the expression of these genes by affecting the binding of transcription factors and chromatin modeling molecules. Furthermore, an interplay between genetic and epigenetic factors may also influence HLA expression. Epigenetic factors such as DNA methylation and non-coding RNA, regulate gene expression without changing the DNA sequence. However, genetic variation may promote or allow genes to escape regulation by epigenetic factors, resulting in altered expression. The HLA system is central to most diseases, therefore, understanding the role of genetics and epigenetics on HLA regulation will tremendously impact healthcare. The knowledge gained from these studies may lead to novel and cost-effective diagnostic approaches and therapeutic interventions. This review discusses the role of non-coding variants on HLA regulation. Furthermore, we discuss the interplay between genetic and epigenetic factors on the regulation of HLA by evaluating literature based on polymorphisms within DNA methylation and miRNA regulatory sites within class I and Class II HLA genes. We also provide insight into the importance of the HLA non-coding genome on disease, discuss ethnic-specific differences across the HLA region and provide guidelines for future HLA studies.

Roles of small peptides encoded by non-coding RNAs in tumor invasion and migration.

Non-coding RNAs (ncRNAs), which are usually considered not to encode proteins, are widely involved in important activities including signal transduction and cell proliferation. However, recent studies have shown that small peptides encoded by ncRNAs (SPENs) have important roles in the development of malignant tumors. Some SPENs participate in the regulation of skeleton reorganization, intercellular adhesion, signaling and other processes of tumor cells, with effects on the invasive and migratory abilities of the cells. Therefore, SPENs have potential applications as therapeutic targets and biomarkers of malignant tumors. Invasion and migration of malignant tumor cells are the main reasons for poor prognosis of cancer patients and represent the most challenging aspects of treatment of malignant tumors. Currently, the main treatments for tumors include surgery, radiotherapy, targeted drug therapy. Surgery, however, is reserved for early stages of cancer and carries risks and costs. Radiotherapy and targeted therapy have serious side effects. This review describes the mechanisms of SPENs and their roles in tumor invasion and migration, with the aim of providing new targets for tumor diagnosis and treatment.

The LINC00319 binding to STAT3 promotes the cell proliferation, migration, invasion and EMT process in oral squamous cell carcinoma.

BACKGROUND: Long non-coding RNA LINC00319 has been implicated in the progression of various cancers, including oral squamous cell carcinoma (OSCC). While our previous work has revealed some aspects of LINC00319's role in OSCC, including its upregulation and involvement in a competing endogenous RNA (ceRNA) mechanism, the full extent of its functions and regulatory mechanisms in OSCC progression remain to be fully elucidated. OBJECTIVE: This study aimed to investigate the function of LINC00319 in OSCC and its potential interaction with the STAT3 signaling pathway, thus uncovering novel regulatory mechanisms and therapeutic targets. METHODS: Bioinformatics analysis was performed using TCGA data to evaluate LINC00319 expression in OSCC tissues and its correlation with STAT3 signaling. The direct binding between LINC00319 and STAT3 was examined by RNA pull-down, FISH, and RIP assays. Functional experiments, including CCK-8, transwell migration and invasion assays, and western blot analysis of EMT markers and STAT3 pathway activation, were conducted to assess the effects of LINC00319 on OSCC cell behaviors and its interaction with the STAT3 signaling pathway. In vivo xenograft models were established to validate the role of LINC00319 in tumor growth and STAT3 activation. RESULTS: LINC00319 expression was significantly upregulated in OSCC tissues compared to normal tissues, and high LINC00319 expression correlated with STAT3 signaling activation. Mechanistically, LINC00319 directly bound to STAT3 protein and promoted its phosphorylation at Tyr705. LINC00319 overexpression enhanced, while its knockdown suppressed, the proliferation, migration, invasion, and EMT of OSCC cells. These oncogenic effects were mediated through STAT3 activation and could be reversed by the STAT3 inhibitor stattic. In vivo experiments further confirmed that LINC00319 silencing inhibited tumor growth and STAT3 phosphorylation. CONCLUSION: This study uncovers that LINC00319 promotes OSCC tumorigenesis by directly binding to and activating STAT3 signaling. These findings provide new insights into the regulatory mechanisms of STAT3 by long non-coding RNAs and highlight the potential of LINC00319 as a biomarker and therapeutic target in OSCC.

Quantitative detection of circular RNA and microRNA at point-of-care using droplet digital CRISPR/Cas13a platform.

Circular RNA (circRNA) and microRNA (miRNA) are both non-coding RNAs (ncRNAs) that serve as biomarkers for cancer diagnosis and prognosis. Quantitative detection of these ncRNAs is of particular importance to elucidate the functional mechanisms and evaluate their potential as biomarkers. However, the inherent structures of circRNA and miRNA are different from the mRNA, conventional qRT-PCR is unsuitable for the detection of these ncRNAs. Here, we propose a sensitive method for quantitative detection of circRNA and miRNA using polydisperse droplet digital CRISPR/Cas13a (PddCas13a). It can achieve limits of detection (LOD) as low as ∼10 aM without polymerase-based amplification. To efficiently detect the circRNA and miRNA in real samples, we use a chemically modified crRNA to enhance the stability of crRNA and improve the performance of Cas13a in complex environments containing contaminants. By integrating an extraction-free procedure with PddCas13a, we experimentally demonstrate the applicability of PddCas13a by testing clinical samples. Furthermore, we develop an automated and portable instrument for PddCas13a and verify its applicability for the detection of circRNA and miRNA from exosomes in point-of-care (POC) setting. This is the first report to detect the circRNA and miRNA simultaneously in POC setting. We envision this platform could promote the research of ncRNAs.

Non-coding RNAs as potential targets in metformin therapy for cancer.

Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

The clinical value of serum long non-coding RNA human leukocyte antigen complex group 11/microRNA-532-3p in the diagnosis and prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Acute myocardial infarction (AMI) is a cardiovascular disease with the highest morbidity and mortality rate in the world. Several studies have suggested that abnormal regulation of non-coding RNAs (ncRNAs) may play a vital role in the occurrence and progress of AMI. OBJECTIVE: The purpose of this study was to investigate the clinical values of human leukocyte antigen complex group 11 (HCG11) or miR-532-3p in the diagnosis and prognosis of patients with AMI after percutaneous coronary intervention (PCI). METHODS: The clinical data of 100 AMI patients who underwent PCI were analyzed retrospectively. According to whether major adverse cardiovascular events (MACE) occurred after PCI, they were divided into MACE group (n = 38) and non-MACE group (n = 62). Basic clinical data and serum HCG11 and miR-532-3p levels were analyzed. Multivariate Cox regression analysis was performed to evaluate the risk factors for MACE, and the receiver operator characteristic (ROC) curve was constructed to assess the clinical predictive value of HCG11 and miR-532-3p for MACE. RESULTS: Compared with the control group, the serum HCG11 level and miR-532-3p in AMI patients were significantly increased or decreased, and the serum levels of HCG11 and miR-532-3p in the MACE group were significantly increased and decreased, compared with those in non-MACE group. Multivariate Cox regression showed that HCG11 and miR-532-3p were risk factors for MACE occurrence. ROC curve investigated that HCG11 combined with miR-532-3p has accurate predictive value for MACE. CONCLUSION: This study showed that serum HCG11 and miR-532-3p have certain predictive value for MACE after PCI in patients with AMI.

Exploration and validation of ceRNA regulatory networks in colorectal cancer based on associations whole transcriptome sequencing.

Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), round RNAs (circRNAs), and microRNAs (miRNAs) using whole-transcriptome sequencing and generated competing endogenous RNA (ceRNA) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mRNAs (DEmRNAs), 77 DE miRNAs (DEmiRNAs). 2852 DE lncRNAs (DElncRNAs) and 1477 DE circRNAs (DEcircRNAs). In addition, utilizing co-DE analysis, we generated the ceRNA axis. Subsequently, we employed the ceRNA axis to identify essential genes and corresponding associations with lncRNAs, circRNAs, and miRNAs in CRC. ceRNA regulatory network including mRNA-miRNA-lncRNA and mRNA-miRNA-circRNA. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of RNA sequencing (RNA-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found siRNA-based KPNA2 depletion reduces bladder cancer cells' viability, migratory, and proliferative activities, which showed that the DEmRNA profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These evidences highlight the ceRNA regulatory mechanisms in CRC and will aid future research into the molecular mechanisms behind colorectal cancer prevention and treatment.

Identification of LINC02454-related key pathways and genes in papillary thyroid cancer by weighted gene coexpression network analysis (WGCNA).

BACKGROUND: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. METHODS: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. RESULTS: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM - receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. CONCLUSIONS: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

Therapeutic Antisense Oligonucleotides in Oncology: From Bench to Bedside.

Advancements in our comprehension of tumor biology and chemoresistance have spurred the development of treatments that precisely target specific molecules within the body. Despite the expanding landscape of therapeutic options, there persists a demand for innovative approaches to address unmet clinical needs. RNA therapeutics have emerged as a promising frontier in this realm, offering novel avenues for intervention such as RNA interference and the utilization of antisense oligonucleotides (ASOs). ASOs represent a versatile class of therapeutics capable of selectively targeting messenger RNAs (mRNAs) and silencing disease-associated proteins, thereby disrupting pathogenic processes at the molecular level. Recent advancements in chemical modification and carrier molecule design have significantly enhanced the stability, biodistribution, and intracellular uptake of ASOs, thereby bolstering their therapeutic potential. While ASO therapy holds promise across various disease domains, including oncology, coronary angioplasty, neurological disorders, viral, and parasitic diseases, our review manuscript focuses specifically on the application of ASOs in targeted cancer therapies. Through a comprehensive examination of the latest research findings and clinical developments, we delve into the intricacies of ASO-based approaches to cancer treatment, shedding light on their mechanisms of action, therapeutic efficacy, and prospects.

RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.

Transcription factors (TFs) regulate gene expression by binding with varying strengths to DNA via their DNA-binding domain. Additionally, some TFs also interact with RNA, which modulates transcription factor binding to chromatin. However, whether RNA-mediated TF binding results in differential transcriptional outcomes remains unknown. In this study, we demonstrate that estrogen receptor α (ERα), a ligand-activated TF, interacts with RNA in a ligand-dependent manner. Defects in RNA binding lead to genome-wide loss of ERα recruitment, particularly at weaker ERα-motifs. Furthermore, ERα mobility in the nucleus increases in the absence of its RNA-binding capacity. Unexpectedly, this increased mobility coincides with robust polymerase loading and transcription of ERα-regulated genes that harbor low-strength motifs. However, highly stable binding of ERα on chromatin negatively impacts ligand-dependent transcription. Collectively, our results suggest that RNA interactions spatially confine ERα on low-affinity sites to fine-tune gene transcription.

The plasma miRNAome in ADNI: Signatures to aid the detection of at-risk individuals.

INTRODUCTION: MicroRNAs are short non-coding RNAs that control proteostasis at the systems level and are emerging as potential prognostic and diagnostic biomarkers for Alzheimer's disease (AD). METHODS: We performed small RNA sequencing on plasma samples from 847 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. RESULTS: We identified microRNA signatures that correlate with AD diagnoses and help predict the conversion from mild cognitive impairment (MCI) to AD. DISCUSSION: Our data demonstrate that plasma microRNA signatures can be used to not only diagnose MCI, but also, critically, predict the conversion from MCI to AD. Moreover, combined with neuropsychological testing, plasma microRNAome evaluation helps predict MCI to AD conversion. These findings are of considerable public interest because they provide a path toward reducing indiscriminate utilization of costly and invasive testing by defining the at-risk segment of the aging population. HIGHLIGHTS: We provide the first analysis of the plasma microRNAome for the ADNI study. The levels of several microRNAs can be used as biomarkers for the prediction of conversion from MCI to AD. Adding the evaluation of plasma microRNA levels to neuropsychological testing in a clinical setting increases the accuracy of MCI to AD conversion prediction.