ncRNA Expression Research Articles

Non-Coding RNA as Biomarkers and Their Role in the Pathogenesis of Gastric Cancer—A Narrative Review

Non-coding RNAs (ncRNAs) represent a broad family of molecules that regulate gene expression, including microRNAs, long non-coding RNAs and circular RNAs, amongst others. Dysregulated expression of ncRNAs alters gene expression, which is implicated in the pathogenesis of several malignancies and inflammatory diseases. Gastric cancer is the fifth most frequently diagnosed cancer and the fourth most common cause of cancer-related death. Studies have found that altered expression of ncRNAs may contribute to tumourigenesis through regulating proliferation, apoptosis, drug resistance and metastasis. This review describes the potential use of ncRNAs as diagnostic and prognostic biomarkers. Moreover, we discuss the involvement of ncRNAs in the pathogenesis of gastric cancer, including their interactions with the members of major signalling pathways.

Role of non‑coding RNAs in UV‑induced radiation effects (Review).

Ultraviolet (UV) is divided into UVA (long-wave, 320-400 nm), UVB (middle-wave, 280-320 nm) and UVC (short-wave, 100-280 nm) based on wavelength. UV radiation (UVR) from sunlight (UVA + UVB) is a major cause of skin photodamage including skin inflammation, aging and pigmentation. Accidental exposure to UVC burns the skin and induces skin cancer. In addition to the skin, UV radiation can also impair visual function. Non-coding RNAs (ncRNAs) are a class of functional RNAs that do not have coding activity but can control cellular processes at the post-transcriptional level, including microRNA (miRNA), long non-coding RNA (lncRNA) and circulatory RNA (circRNA). Through a review of the literature, it was determined that UVR can affect the expression of various ncRNAs, and that this regulation may be wavelength specific. Functionally, ncRNAs participate in the regulation of photodamage through various pathways and play pathogenic or protective regulatory roles. In addition, ncRNAs that are upregulated or downregulated by UVR can serve as biomarkers for UV-induced diseases, aiding in diagnosis and prognosis assessment. Therapeutic strategies targeting ncRNAs, including the use of natural drugs and their extracts, have shown protective effects against UV-induced photodamage. In the present review, an extensive summarization of previous studies was performed and the role and mechanism of ncRNAs in UV-induced radiation effects was reviewed to aid in the diagnosis and treatment of UV-related diseases.

DNA Framework-Based Programmable Atom-Like Nanoparticles for Non-Coding RNA Recognition and Differentiation of Cancer Cells.

The cooperative diagnosis of non-coding RNAs (ncRNAs) can accurately reflect the state of cell differentiation and classification, laying the foundation of precision medicine. However, there are still challenges in simultaneous analyses of multiple ncRNAs and the integration of biomarker data for cell typing. In this study, DNA framework-based programmable atom-like nanoparticles (PANs) are designed to develop molecular classifiers for intra-cellular imaging of multiple ncRNAs associated with cell differentiation. The PANs-based molecular classifier facilitates signal amplification through the catalytic hairpin assembly. The interaction between PAN reporters and ncRNAs enables high-fidelity conversion of ncRNAs expression level into binding events, and the assessment of in situ ncRNAs levels via measurement of the fluorescent signal changes of PAN reporters. Compared to non-amplified methods, the detection limits of PANs are reduced by four orders of magnitude. Using human gastric cancer cell lines as a model system, the PANs-based molecular classifier demonstrates its capacity to measure multiple ncRNAs in living cells and assesses the degree of cell differentiation. This approach can serve as a universal strategy for the classification of cancer cells during malignant transformation and tumor progression.

Диагностический потенциал регуляторных не кодирующих белок РНК при хроническом лимфоцитарном лейкозе

This paper reviews current knowledge about regulatory non-coding protein RNAs (ncRNAs) involved in the pathogenesis of chronic lymphocytic leukemia (CLL) and their potential capabilities as diagnostic markers. Diversity of clinical course as well as absence of detectable chromosomal aberrations and somatic mutations in 20 % of patients increase the interest to study the epigenetic aspects of pathogenesis. In this context, ncRNAs are believed to be promising diagnostic markers since their expression is commonly tissue-specific and they are quite stable in body fluids. Among the regulatory ncRNAs involved in the CLL pathogenesis, microRNAs and long (lncRNAs) have been most studied, whereas ring-like, or circulatory, ncRNAs (circRNAs) require further analysis. Aberrant expression of ncRNAs may account for the resistance to treatment in CLL patients without detected genomic abnormalities. Bioinformatics analysis of RNA sequencing databases allows to isolate novel candidate ncRNA molecules, including those associated with RNA-mediated suppression of the Piwi protein-interacting transposons. This paper proposes new independent predictive models based on the expression of 2 (LNC-KIA1755-4, LNC-IRF2-32-LNCRNA), 4 (miR-125b, miR-15b, miR-181c, miR-412), and 6 (PRKCQ, TRG.AS1, LNC00467, LNC01096, PCAT6, SBF2.AS1) simultaneously assessed different ncRNAs. Since risk- and stage classification of hematological malignancies is performed not only on the basis of clinical but also molecular genetic markers, the monitoring of regulatory ncRNA expression can provide an additional tool for more effective stratification of patients. The present review is concerned with the methodology issues in analytical procedures which impede widespread use of laboratory ncRNA tests.

Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application.

Many investigations have evaluated the expression of noncoding RNAs (ncRNAs) as well as their related molecular functions and biological machineries in individuals with alcohol dependence. Alcohol dependence may be one of the most prevailing psychological disorders globally, and its pathogenesis is intricate and inadequately comprehended. There is substantial evidence indicating significant links between multiple genetic factors and the development of alcohol dependence. In particular, the critical roles of ncRNAs have been emphasized in the pathology of mental illnesses, probably including alcohol dependence. In the comprehension of the action of ncRNAs and their machineries of modification, furthermore, they have emerged as therapeutic targets for a variety of psychiatric illnesses, including alcohol dependence. It is worth mentioning that the dysregulated expression of ncRNAs has been regularly detected in individuals with alcohol dependence. An in-depth knowledge of the roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a more profound understanding of the practical roles of ncRNAs might make important contributions to the precise diagnosis and/or actual management of alcohol dependence. Here, in this review, we mostly focused on up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in individuals with alcohol dependence. Then, we present prospects for future research and therapeutic applications with a novel concept of the engram system.

Value of Non-Coding RNA Expression in Biofluids to Identify Patients at Low Risk of Pathologies Associated with Pregnancy.

Pregnancy-related complications (PRC) impact maternal and fetal morbidity and mortality and place a huge burden on healthcare systems. Thus, effective diagnostic screening strategies are crucial. Currently, national and international guidelines define patients at low risk of PRC exclusively based on their history, thus excluding the possibility of identifying patients with de novo risk (patients without a history of disease), which represents most women. In this setting, previous studies have underlined the potential contribution of non-coding RNAs (ncRNAs) to detect patients at risk of PRC. However, placenta biopsies or cord blood samples are required, which are not simple procedures. Our review explores the potential of ncRNAs in biofluids (fluids that are excreted, secreted, or developed because of a physiological or pathological process) as biomarkers for identifying patients with low-risk pregnancies. Beyond the regulatory roles of ncRNAs in placental development and vascular remodeling, we investigated their specific expressions in biofluids to determine favorable pregnancy outcomes as well as the most frequent pathologies of pregnant women. We report distinct ncRNA panels associated with PRC based on omics technologies and subsequently define patients at low risk. We present a comprehensive analysis of ncRNA expression in biofluids, including those using next-generation sequencing, shedding light on their predictive value in clinical practice. In conclusion, this paper underscores the emerging significance of ncRNAs in biofluids as promising biomarkers for risk stratification in PRC. The investigation of ncRNA expression patterns and their potential clinical applications is of diagnostic, prognostic, and theragnostic value and paves the way for innovative approaches to improve prenatal care and maternal and fetal outcomes.

Construction and analysis of a network of exercise-induced mitochondria-related non-coding RNA in the regulation of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a major factor in the development of heart failure. Mitochondria play a crucial role in regulating insulin resistance, oxidative stress, and inflammation, which affect the progression of DCM. Regular exercise can induce altered non-coding RNA (ncRNA) expression, which subsequently affects gene expression and protein function. The mechanism of exercise-induced mitochondrial-related non-coding RNA network in the regulation of DCM remains unclear. This study seeks to construct an innovative exercise-induced mitochondrial-related ncRNA network. Bioinformatic analysis of RNA sequencing data from an exercise rat model identified 144 differentially expressed long non-coding RNA (lncRNA) with cutoff criteria of p< 0.05 and fold change ≥1.0. GSE6880 and GSE4745 were the differentially expressed mRNAs from the left ventricle of DCM rat that downloaded from the GEO database. Combined with the differentially expressed mRNA and MitoCarta 3.0 dataset, the mitochondrial located gene Pdk4 was identified as a target gene. The miRNA prediction analysis using miRanda and TargetScan confirmed that 5 miRNAs have potential to interact with the 144 lncRNA. The novel lncRNA-miRNA-Pdk4 network was constructed for the first time. According to the functional protein association network, the newly created exercise-induced ncRNA network may serve as a promising diagnostic marker and therapeutic target, providing a fresh perspective to understand the molecular mechanism of different exercise types for the prevention and treatment of diabetic cardiomyopathy.

Comprehensive investigation of differentially expressed ncRNAs, mRNAs, and their ceRNA networks in the regulation of shell color formation in clam, Cyclina sinensis

Noncoding RNAs (ncRNAs) have gained significant attention in recent years due to their crucial roles in various biological processes. However, our understanding of the expression and functions of ncRNAs in Cyclina sinensis, an economically important marine bivalve, remains limited. This study aimed to address this knowledge gap by systematically identifying ncRNAs in the mantles of C. sinensis with purple and white shells. Through our analysis, we identified a differential expression of 1244 mRNAs, 196 lncRNAs, 49 circRNAs, and 23 miRNAs between purple- and white-shell clams. Functional enrichment analysis revealed the involvement of these differentially expressed ncRNAs in biomineralization and pigmentation processes. To gain further insights into the regulatory mechanisms underlying shell color formation, we established competitive endogenous RNA (ceRNA) networks. These networks allowed us to identify targeted differentially expressed miRNAs (DEMis) and genes associated with shell color formation. Based on the ceRNA networks, we obtained an up-down-up lncRNA-miRNA-mRNA network consisting of 13 upregulated lncRNAs and a circRNA-miRNA-mRNA network comprising three upregulated circRNAs (novel_circ_0004787, novel_circ_0001165, novel_circ_0000245). Through these networks, we identified and selected an upregulated novel gene (evm.TU.Hic_asm_7.988) and a downregulated sponge miRNA (hru-miR-1985) as potential contributors to shell color regulation. In summary, the present investigation offers a comprehensive analysis of ncRNA catalogs expressed in the clam mantle of C. sinensis. The findings enhance our comprehension of the molecular mechanisms governing shell coloration and offer new perspectives for selective breeding of C. sinensis in the future.

Transcriptional Changes in Damask Rose Suspension Cell Culture Revealed by RNA Sequencing.

Damask roses (Rosa x damascena) are widely used in cosmetics and pharmaceutics. Here, we established an in vitro suspension cell culture for calli derived from damask rose petals. We analyzed rose suspension cell transcriptomes obtained at two different time points by RNA sequencing to reveal transcriptional changes during rose suspension cell culture. Of the 580 coding RNAs (1.3%) highly expressed in the suspension rose cells, 68 encoded cell wall-associated proteins. However, most RNAs encoded by the chloroplasts and mitochondria are not expressed. Many highly expressed coding RNAs are involved in translation, catalyzing peptide synthesis in ribosomes. Moreover, the amide metabolic process producing naturally occurring alkaloids was the most abundant metabolic process during the propagation of rose suspension cells. During rose cell propagation, coding RNAs involved in the stress response were upregulated at an early stage, while coding RNAs associated with detoxification and transmembrane transport were upregulated at the late stage. We used transcriptome analyses to reveal important biological processes and molecular mechanisms during rose suspension cell culture. Most non-coding (nc) RNAs were not expressed in the rose suspension cells, but a few ncRNAs with unknown functions were highly expressed. The expression of ncRNAs and their target coding RNAs was highly correlated. Taken together, we revealed significant biological processes and molecular mechanisms occurring during rose suspension cell culture using transcriptome analyses.

Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs

Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p < 0.0001] and plasma-derived extracellular vesicles (AUC = 0.981, p = 0.0002). Overall, Y RNA may be more resistant to hypoxic stress in the metastatic than the non-metastatic state for COM. However, further investigation is required to elucidate the biological functions of Y RNA under hypoxic conditions.

Epigenetic Regulation of Autophagy in Bone Metabolism

Abstract The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects like bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's impact on bone health varies depending on factors such as regulation, cell type, environmental cues, and physiological context. Despite being traditionally considered a cytoplasmic process, autophagy is subject to transcriptional and epigenetic regulation within the nucleus. However, the precise influence of epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNA (ncRNA) expression, on cellular fate remains incompletely understood. The interplay between autophagy and epigenetic modifications adds complexity to bone cell regulation. This article provides an in-depth exploration of the intricate interplay between these two regulatory paradigms, with a focus on the epigenetic control of autophagy in bone metabolism. Such an understanding enhances our knowledge of bone metabolism-related disorders and offers insights for the development of targeted therapeutic strategies.

Relationship between Biochemical Pathways and Non-Coding RNAs Involved in the Progression of Diabetic Retinopathy.

Diabetic retinopathy (DR) is a progressive blinding disease, which affects the vision and quality of life of patients, and it severely impacts the society. This complication, caused by abnormal glucose metabolism, leads to structural, functional, molecular, and biochemical abnormalities in the retina. Oxidative stress and inflammation also play pivotal roles in the pathogenic process of DR, leading to mitochondrial damage and a decrease in mitochondrial function. DR causes retinal degeneration in glial and neural cells, while the disappearance of pericytes in retinal blood vessels leads to alterations in vascular regulation and stability. Clinical changes include dilatation and blood flow changes in response to the decrease in retinal perfusion in retinal blood vessels, leading to vascular leakage, neovascularization, and neurodegeneration. The loss of vascular cells in the retina results in capillary occlusion and ischemia. Thus, DR is a highly complex disease with various biological factors, which contribute to its pathogenesis. The interplay between biochemical pathways and non-coding RNAs (ncRNAs) is essential for understanding the development and progression of DR. Abnormal expression of ncRNAs has been confirmed to promote the development of DR, suggesting that ncRNAs such as miRNAs, lncRNAs, and circRNAs have potential as diagnostic biomarkers and theranostic targets in DR. This review provides an overview of the interactions between abnormal biochemical pathways and dysregulated expression of ncRNAs under the influence of hyperglycemic environment in DR.

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.

RNA Pol II Assembly Affects ncRNA Expression.

RNA pol II assembly occurs in the cytoplasm before translocation of the enzyme to the nucleus. Affecting this assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In this work, we show that impairment of RNA pol II assembly leads to a decrease in cryptic non-coding RNAs (preferentially CUTs and SUTs). This alteration is partially restored upon overcoming the assembly defect. Notably, this drop in ncRNAs is only partially dependent on the nuclear exosome, which suggests a major specific effect of enzyme assembly. Our data also point out a defect in transcription termination, which leads us to propose that CTD phosphatase Rtr1 could be involved in this process.

Post-Radiotherapy Exosomal Non-Coding RNA and Hemograms for Early Death Prediction in Patients with Cervical Cancer.

Concurrent chemo-radiotherapy (CCRT) is linked with accelerated disease progression and early death (ED) in various cancers. This study aimed to assess the association of plasma levels of exosomal non-coding ribonucleic acid (RNA) (ncRNA) and blood cell dynamics with ED prediction in patients with cervical cancer undergoing CCRT. Using propensity score matching, a comparison of complete blood counts (CBCs) was performed among 370 CCRT-treated patients. Differences in ncRNA and messenger RNA (mRNA) expression before and after CCRT in 84 samples from 42 patients (cohort 2) were represented as logarithmic fold change (log2FC). Networks were constructed to link the CBCs to the RNAs whose expression correlated with ED. From the key RNAs selected using multiple regression of all RNA combinations in the network, CBC dynamics-associated ncRNAs were functionally characterized using an enrichment analysis. Cohort 1 (120 patients) exhibited a correlation between elevated absolute neutrophil counts (ANC) and ED. Cohort 2 exhibited a prevalence of microRNA (miR)-574-3p and long intergenic non-protein coding (LINC)01003 ncRNA, whose expression correlated with ANC and hemoglobin values, respectively. Conversely, acyl-coenzyme A thioesterase 9 (ACOT9) mRNA was relevant to all CBC components. An integrative analysis of post-CCRT ncRNA levels and CBC values revealed that the patients with miR-574-3p-LINC01003-ACOT9 log2FC) < 0 had a better prospect of 30-month disease-specific survival. These findings indicate that miR-574-3p and LINC01003 could serve as ED prognostic biomarkers.

Comparison of mRNA and ncRNA expression profiles in colon cancer patients with system biology approach between 2020 and 2021

Comparison of mRNA and ncRNA expression profiles in colon cancer patients with system biology approach between 2020 and 2021

YRNA and tRNA fragments can differentiate benign from malignant canine mammary gland tumors

Mammary gland tumors (MGT) are the most common tumors in sexually intact female dogs. The functional regulation of miRNAs, a type of noncoding RNAs (ncRNAs), in canine MGT has been extensively investigated. However, the expression of other ncRNAs, such as YRNAs and transfer RNA–derived fragments (tRFs) in canine MGT is unknown. We investigated ncRNAs other than miRNAs from our small RNA project (PRJNA716131) in different canine MGT histologic subtypes. This study included benign tumors (benign mixed tumor, complex adenoma) and malignant tumors (carcinoma in benign tumor and carcinoma with metastasis) samples. Aberrantly expressed ncRNAs were examined by comparisons among MGT subtypes. The relative expression trends were validated in canine MGT tissues, plasma, extracellular vesicles, and MGT cell lines using quantitative reverse transcription PCR. Three aberrantly expressed ncRNAs were identified by comparisons among MGT subtypes. YRNA and tRNA-Gly-GCC distinguished benign mixed tumor from other MGT histologic subtypes, while tRNA-Val differentiated complex adenoma, carcinoma in benign tumors, and carcinoma with metastasis. The ROC curve of the three ncRNAs showed they might be potential biomarkers to discriminate malignant from benign MGT. YRNA and tRFs expression levels were decreased in metastatic compared with primary canine MGT cell lines. To the best of our knowledge, this is the first investigation of YRNA and tRFs in canine MGT. The three identified ncRNAs may be biomarkers for differentiating MGT histologic subtypes. Suggested Reviewers: Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporatio

KDM3B Single-Nucleotide Polymorphisms Impact Radiation Therapy Toxicity Through Circular RNA-Mediated KDM3B Expression and Inflammatory Responses

PurposeGenome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with radiotherapy (RT) toxicities in prostate cancer patients. SNP rs17599026 in intron 21 of KDM3B is significantly associated with the development of late urinary toxicity, specifically in the increase in urinary frequency two years after RT compared with pre-treatment conditions. The present study aimed to provide mechanistic insights for this association. Methods and MaterialsUsing human tissues and cell lines, we examined the protein expression of KDM3B and molecular mechanisms underlying the SNP modulation by variants of KDM3B SNP alleles. In animals with normal and heterozygous expressions of Kdm3b, we examined the relationship between Kdm3b expression and radiation toxicity. ResultsKDM3B rs17599026 lies in a motif important for circular RNA expression which is responsible for sponging miRNAs to regulate KDM3B expression. Using a murine model with heterozygous deletion of Kdm3b gene, we found that lower Kdm3b expression is associated with altered pattern of urination after bladder irradiation, which is related to differential degrees of tissue inflammation as measured by analyses of gene expression, lymphocyte infiltration, and non-invasive ultrasound imaging. ConclusionsKDM3B SNPs can impact its expression through regulating noncoding (nc) RNA expression. Differential KDM3B expression underlies radiation toxicity through tissue inflammation at the molecular and physiological level. Our study outcome offers a foundation for mechanism-based mitigation for radiation toxicity for prostate cancer survivors.

NcRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32969 entries involving 10480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

Non-coding RNA-mediated endothelial-to-mesenchymal transition in human diabetic cardiomyopathy, potential regulation by DNA methylation

AimsDiabetic cardiomyopathy (DCM) is a major complication of diabetes and a risk factor for cardiovascular disease. Endothelial dysfunction is central to DCM, and endothelial-to-mesenchymal transition (EndMT) is a key form of endothelial dysfunction in diabetes. EndMT in DCM has been well-studied in model systems and has been found to be epigenetically regulated by non-coding RNAs (ncRNAs). However, EndMT in DCM and its associated epigenetic changes need further characterization in human patients. It is also not known if ncRNAs are affected by changes in DNA methylation in DCM. This study aims to confirm in human hearts, the findings from animal and cell studies, and potentially provide novel insight into interactions between DNA methylation and ncRNAs in EndMT in DCM.Methods and resultsHeart tissues were collected from autopsy patients, fixed in formalin, and embedded in paraffin. Thin sections from paraffin-embedded tissues were used for histology and immunofluorescence analyses, where we confirmed that diabetic patients showed increased cardiac fibrosis that EndMT had occurred. Tissue curls from the paraffin-embedded tissues were used for RT-qPCR and methylation analyses. RT-qPCR quantitatively showed that EndMT occurs in the hearts of diabetics, and that EndMT in human hearts corresponded to changes in key ncRNAs. Methylation analysis showed that some of the EndMT-related ncRNAs were regulated by DNA promoter methylation, while others may be regulated through different epigenetic mechanisms.ConclusionsWe show that EndMT is a relevant pathological process in human hearts during DCM, and that its occurrence coincides with changes in relevant ncRNAs. We further find that interplay between DNA methylation and certain ncRNAs involved in the regulation of EndMT may contribute to the observed changes in ncRNA expression. These findings reinforce the role of EndMT in patients afflicted with DCM and underscore the complexities and importance of the interactions between different facets of epigenetic regulation.