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International Journal of Molecular... Jun 2024A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA...
A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation was analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors-of both primitive endocardial tubes-committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant novelty, our results revealed that miR-1 increased , and , while this microRNA diminished and expressions during early differentiation of the cardiac sinoatrial region. Furthermore, we observed in this developmental context that miR-1 upregulated and and downregulated , which are three crucial factors in the retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacted with and /, as well as with /, which are three key factors actively involved in regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in the early differentiation of the cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and , fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.
Topics: Animals; MicroRNAs; Epigenesis, Genetic; Cell Differentiation; Gene Expression Regulation, Developmental; Chick Embryo; MEF2 Transcription Factors; Sinoatrial Node; Signal Transduction; Heart
PubMed: 38928314
DOI: 10.3390/ijms25126608 -
International Journal of Molecular... Jun 2024This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in...
This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A ( = 130), luminal B ( = 196, including HER2-, = 100; HER2+, = 96), HER2+ ( = 36), and TNBC ( = 43); they underwent surgery, during which tumor tissue was removed along with a margin of healthy tissue (control material). The molecular analysis included a microarray profile of mRNAs and miRNAs associated with the dopaminergic system, a real-time polymerase chain reaction preceded by reverse transcription for selected genes, and determinations of their concentration using enzyme-linked immunosorbent assay (ELISA). The conducted statistical analysis showed that five mRNAs statistically significantly differentiated breast cancer sections regardless of subtype compared to control samples; these were dopamine receptor 2 (), dopamine receptor 3 (), dopamine receptor 25 (), transforming growth factor beta 2 (), and caveolin 2 (). The predicted analysis showed that hsa-miR-141-3p can regulate the expression of and , whereas hsa-miR-4441 is potentially engaged in the expression regulation of and . In addition, the expression pattern of mRNA can also be regulated by has-miR-16-5p. The overexpression of DRD2 and DRD3, with concomitant silencing of DRD5 expression, confirms the presence of dopaminergic abnormalities in breast cancer patients. Moreover, these abnormalities may be the result of miR-141-3P, miR-16-5p, and miR-4441 activity, regulating proliferation or metastasis.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Gene Expression Regulation, Neoplastic; Middle Aged; Dopamine; Adult; Gene Expression Profiling; Aged; RNA, Messenger; Receptors, Dopamine D3; Receptors, Dopamine D2; Transforming Growth Factor beta2
PubMed: 38928253
DOI: 10.3390/ijms25126546 -
International Journal of Molecular... Jun 2024Chronic liver diseases, fibrosis, cirrhosis, and HCC are often a consequence of persistent inflammation. However, the transition mechanisms from a normal liver to...
Chronic liver diseases, fibrosis, cirrhosis, and HCC are often a consequence of persistent inflammation. However, the transition mechanisms from a normal liver to fibrosis, then cirrhosis, and further to HCC are not well understood. This study focused on the role of the tumor stem cell protein doublecortin-like kinase 1 (DCLK1) in the modulation of molecular factors in fibrosis, cirrhosis, or HCC. Serum samples from patients with hepatic fibrosis, cirrhosis, and HCC were analyzed via ELISA or NextGen sequencing and were compared with control samples. Differentially expressed (DE) microRNAs (miRNA) identified from these patient sera were correlated with DCLK1 expression. We observed elevated serum DCLK1 levels in fibrosis, cirrhosis, and HCC patients; however, TGF-β levels were only elevated in fibrosis and cirrhosis. While DE miRNAs were identified for all three disease states, was elevated in fibrosis but was significantly increased further in cirrhosis. Additionally, and were upregulated when DCLK1 was high, while was downregulated. This work distinguishes DCLK1 and miRNAs' potential role in different axes promoting inflammation to tumor progression and may serve to identify biomarkers for tracking the progression from pre-neoplastic states to HCC in chronic liver disease patients as well as provide targets for treatment.
Topics: Humans; Doublecortin-Like Kinases; MicroRNAs; Protein Serine-Threonine Kinases; Intracellular Signaling Peptides and Proteins; Liver Neoplasms; Liver Cirrhosis; Inflammation; Male; Carcinoma, Hepatocellular; Female; Chronic Disease; Liver Diseases; Middle Aged; Carcinogenesis; Aged; Biomarkers, Tumor
PubMed: 38928187
DOI: 10.3390/ijms25126481 -
International Journal of Molecular... Jun 2024Sepsis, a life-threatening condition caused by the body's dysregulated response to infection, presents a significant challenge in clinical management. Timely and... (Review)
Review
Sepsis, a life-threatening condition caused by the body's dysregulated response to infection, presents a significant challenge in clinical management. Timely and accurate diagnosis is paramount for initiating appropriate interventions and improving patient outcomes. In recent years, there has been growing interest in identifying biomarkers that can aid in the early detection and prognostication of sepsis. MicroRNAs (miRNAs) have emerged as potential biomarkers for sepsis due to their involvement in the regulation of gene expression and their stability in various biological fluids, including blood. MiRNAs are small non-coding RNA molecules that play crucial roles in post-transcriptional gene regulation by binding to target messenger RNAs (mRNAs), leading to mRNA degradation or translational repression. The diagnostic and prognostic potential of miRNAs in sepsis stems from their ability to serve as sensitive and specific biomarkers reflective of the underlying pathophysiological processes. Compared to traditional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), miRNAs offer several advantages, including their early and sustained elevation during sepsis, as well as their stability in stored samples, making them attractive candidates for clinical use. However, despite their promise, the clinical translation of miRNAs as sepsis biomarkers faces several challenges. These include the need for standardized sample collection and processing methods, the identification of optimal miRNA panels or signatures for differentiating sepsis from other inflammatory conditions, and the validation of findings across diverse patient populations and clinical settings. In conclusion, miRNAs hold great promise as diagnostic and prognostic biomarkers for sepsis, offering insights into the underlying molecular mechanisms and potential therapeutic targets. However, further research is needed to overcome existing challenges and realize the full clinical utility of miRNAs in improving sepsis outcomes.
Topics: Humans; Sepsis; Biomarkers; MicroRNAs; Prognosis; Animals; Gene Expression Regulation
PubMed: 38928179
DOI: 10.3390/ijms25126476 -
International Journal of Molecular... Jun 2024The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation...
The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) ( < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.
Topics: Animals; Fetal Growth Retardation; DNA Methylation; Swine; Female; Pregnancy; Placenta; Gene Expression Profiling; Protein Interaction Maps; Epigenesis, Genetic; MicroRNAs; Transcriptome; Gene Regulatory Networks
PubMed: 38928167
DOI: 10.3390/ijms25126462 -
International Journal of Molecular... Jun 2024Osteoarthritis (OA) is a degenerative joint disorder characterized by the progressive deterioration of articular cartilage driven and sustained by catabolic and...
Osteoarthritis (OA) is a degenerative joint disorder characterized by the progressive deterioration of articular cartilage driven and sustained by catabolic and inflammatory processes that lead to pain and functional impairment. Adipose-derived stem cells (ASCs) have emerged as a promising therapeutic strategy for OA due to their regenerative potential, which mainly relies on the adaptive release of paracrine molecules that are soluble or encapsulated in extracellular vesicles (EVs). The biological effects of EVs specifically depend on their cargo; in particular, microRNAs (miRNAs) can specifically modulate target cell function through gene expression regulation. This study aimed to investigate the impact of collection site (abdominal vs. peri-trochanteric adipose tissue) and collection method (surgical excision vs. lipoaspiration) on the miRNAs profile in ASC-derived EVs and their potential implications for OA therapy. EV-miRNA cargo profiles from ASCs of different origins were compared. An extensive bioinformatics search through experimentally validated and OA-related targets, pathways, and tissues was conducted. Several miRNAs involved in the restoration of cartilage homeostasis and in immunomodulation were identified in all ASC types. However, EV-miRNA expression profiles were affected by both the tissue-harvesting site and procedure, leading to peculiar characteristics for each type. Our results suggest that adipose-tissue-harvesting techniques and the anatomical site of origin influence the therapeutic efficacy of ASC-EVs for tissue-specific regenerative therapies in OA, which warrants further investigation.
Topics: Humans; Extracellular Vesicles; MicroRNAs; Mesenchymal Stem Cells; Adipose Tissue; Osteoarthritis; Female; Male; Middle Aged; Gene Expression Regulation
PubMed: 38928156
DOI: 10.3390/ijms25126450 -
International Journal of Molecular... Jun 2024This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two...
This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.
Topics: Animals; MicroRNAs; Obesity; Rats; Diet, High-Fat; Male; Podocytes; Rats, Wistar; RNA, Messenger; Kidney Diseases; Gene Expression Profiling; Gene Expression Regulation; Transcriptome; PTEN Phosphohydrolase
PubMed: 38928144
DOI: 10.3390/ijms25126437 -
International Journal of Molecular... Jun 2024Grass Carp Reovirus (GCRV) and (Ah) are the causative agents of haemorrhagic disease in grass carp. This study aimed to investigate the molecular mechanisms and immune... (Comparative Study)
Comparative Study
Grass Carp Reovirus (GCRV) and (Ah) are the causative agents of haemorrhagic disease in grass carp. This study aimed to investigate the molecular mechanisms and immune responses at the miRNA, mRNA, and protein levels in grass carp kidney cells (CIK) infected by Grass Carp Reovirus (GCRV, NV) and (Bacteria, NB) to gain insight into their pathogenesis. Within 48 h of infection with Grass Carp Reovirus (GCRV), 99 differentially expressed microRNA (DEMs), 2132 differentially expressed genes (DEGs), and 627 differentially expressed proteins (DEPs) were identified by sequencing; a total of 92 DEMs, 3162 DEGs, and 712 DEPs were identified within 48 h of infection with . It is worth noting that most of the DEGs in the NV group were primarily involved in cellular processes, while most of the DEGs in the NB group were associated with metabolic pathways based on KEGG enrichment analysis. This study revealed that the mechanism of a grass carp haemorrhage caused by GCRV infection differs from that caused by the infection. An important miRNA-mRNA-protein regulatory network was established based on comprehensive transcriptome and proteome analysis. Furthermore, 14 DEGs and 6 DEMs were randomly selected for the verification of RNA/small RNA-seq data by RT-qPCR. Our study not only contributes to the understanding of the pathogenesis of grass carp CIK cells infected with GCRV and but also serves as a significant reference value for other aquatic animal haemorrhagic diseases.
Topics: Aeromonas hydrophila; Animals; Carps; MicroRNAs; Transcriptome; RNA, Messenger; Reoviridae; Proteomics; Fish Diseases; Gene Expression Profiling; Gram-Negative Bacterial Infections; Cell Line; Reoviridae Infections; Gene Regulatory Networks
PubMed: 38928143
DOI: 10.3390/ijms25126438 -
International Journal of Molecular... Jun 2024Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising... (Review)
Review
Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising biomarkers and therapeutic targets for these conditions. This systematic review conducts a thorough analysis of the literature, with a specific focus on investigating miRNA expression patterns in patients with CAD and hypertension. This review encompasses an unspecified number of eligible studies that employed a variety of patient demographics and research methodologies, resulting in diverse miRNA expression profiles. This review highlights the complex involvement of miRNAs in CAD and hypertension and the potential for advances in diagnostic and therapeutic strategies. Future research endeavors are imperative to validate these findings and elucidate the precise roles of miRNAs in disease progression, offering promising avenues for innovative diagnostic tools and targeted interventions.
Topics: Humans; Coronary Artery Disease; MicroRNAs; Hypertension; Biomarkers; Gene Expression Regulation
PubMed: 38928136
DOI: 10.3390/ijms25126430 -
International Journal of Molecular... Jun 2024Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis' development and progression, including... (Review)
Review
Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis' development and progression, including secondary osteoarthritis' underlying causes. It is important to note that osteoarthritis affects all four tissues: cartilage, bone, joint capsule, and articular apparatus. An increasingly prominent area of research in osteoarthritis regulation is microRNAs (miRNAs), a small, single-stranded RNA molecule that controls gene expression in eukaryotes. We aimed to assess and summarize current knowledge about the mechanisms of the action of miRNAs and their clinical significance. Osteoarthritis (OA) is affected by the interaction between miRNAs and inflammatory processes, as well as cartilage metabolism. MiRNAs also influence cartilage cell apoptosis, contributing to the degradation of the cartilage in OA. Studies have shown that miRNAs may have both an inhibitory and promoting effect on osteoporosis progression through their influence on molecular mechanisms. By identifying these regulators, targeted treatments for osteoarthritis may be developed. In addition, microRNA may also serve as a biomarker for osteoarthritis. By using these biomarkers, the disease could be detected faster, and early intervention can be instituted to prevent mobility loss and slow deterioration.
Topics: MicroRNAs; Humans; Osteoarthritis; Animals; Gene Expression Regulation; Biomarkers; Cartilage, Articular; Chondrocytes
PubMed: 38928059
DOI: 10.3390/ijms25126352