Frontiers in Genetics最新文献

{"title":"Investigation of the role of miRNA variants in neurodegenerative brain diseases.","authors":"Alexandros Frydas, Rita Cacace, Julie van der Zee, Christine Van Broeckhoven, Eline Wauters","doi":"10.3389/fgene.2025.1506169","DOIUrl":"10.3389/fgene.2025.1506169","url":null,"abstract":"<p><strong>Introduction: </strong>miRNAs are small noncoding elements known to regulate different molecular processes, including developmental and executive functions in the brain. Dysregulation of miRNAs could contribute to brain neurodegeneration, as suggested by miRNA profiling studies of individuals suffering from neurodegenerative brain diseases (NBDs). Here, we report rare miRNA variants in patients with Alzheimer's dementia (AD) and frontotemporal dementia (FTD).</p><p><strong>Methods: </strong>We initially used whole exome sequencing data in a subset of FTD patients (n = 209) from Flanders-Belgium. We then performed targeted resequencing of variant-harboring miRNAs in an additional subset of FTD patients (n = 126) and control individuals (n = 426). Lastly, we sequenced the <i>MIR885</i> locus in a Flanders-Belgian AD cohort (n = 947) and a total number of n = 755 controls.</p><p><strong>Results: </strong>WES identified rare seed variants in <i>MIR656, MIR423, MIR122 and MIR885</i> in FTD patients. Most of these miRNAs bind to FTD-associated genes, implicated in different biological pathways. Additionally, some miRNA variants create novel binding sites for genes associated with FTD. Sequencing of the <i>MIR885</i> locus in the AD cohort initially showed a significant enrichment of <i>MIR885</i> variants in AD patients compared to controls (SKAT-O, p-value = 0.026). Genetic association was not maintained when we included sex and <i>APOE</i> status as covariates. Using the miRVaS prediction tool, variants rs897551430 and rs993255773 appeared to evoke significant structural changes in the primary miRNA. These variants are also predicted to strongly downregulate mature <i>miR885</i> levels, in line with what is reported for <i>MIR885</i> in the context of AD.</p><p><strong>Discussion: </strong>Functional investigation of miRNAs/variants described in this study could propose novel miRNA-mediated molecular cascades in FTD and AD pathogenicity. Furthermore, we believe that the genetic evidence presented here suggests a role for <i>MIR885</i> in molecular mechanisms involved in AD and warrants genetic follow-up in larger cohorts to explore this hypothesis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1506169"},"PeriodicalIF":2.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological description and DNA barcoding research of nine <i>Syringa</i> species.","authors":"Meiqi Zhang, Xiaoou Zhai, Lianqing He, Zhen Wang, Huiyan Cao, Panpan Wang, Weichao Ren, Wei Ma","doi":"10.3389/fgene.2025.1544062","DOIUrl":"10.3389/fgene.2025.1544062","url":null,"abstract":"<p><strong>Introduction: </strong><i>Syringa</i> plants are highly valued for their ornamental qualities. However, traditional morphological identification methods are inefficient for discriminating <i>Syringa</i> species. DNA barcoding has emerged as a powerful alternative for species identification, but research on <i>Syringa</i> DNA barcodes is still limited.</p><p><strong>Methods: </strong>This study employed a multi-locus strategy, combining the nuclear <i>ITS2</i> region with chloroplast genome regions <i>psbA-trnH</i>, <i>trnL-trnF</i>, and <i>trnL</i> to evaluate the effectiveness of <i>Syringa</i> DNA barcodes. The assessment involved genetic distance analysis, BLAST searches in NCBI, sequence character analysis, and phylogenetic tree construction, examining both individual and combined sequences.</p><p><strong>Results: </strong>The genetic distance analysis showed that the sequence combination of <i>ITS2</i> + <i>psbA-trnH</i> + <i>trnL-trnF</i> exhibited a variation pattern where most interspecific genetic distances were greater than intraspecific genetic distances. The Wilcoxon signed-rank test results indicated that, except for <i>psbA-trnH</i>, the interspecific differences of the <i>ITS2</i> + <i>psbA-trnH</i> + <i>trnL-trnF</i> sequence were greater than those of all single and combined sequences. BLAST analysis revealed that the identification rate for nine <i>Syringa</i> species using <i>ITS2</i> + <i>psbA-trnH</i> + <i>trnL-trnF</i> could reach 98.97%. The trait-based method also demonstrated that <i>ITS2</i> + <i>psbA-trnH</i> + <i>trnL-trnF</i> could effectively identify the nine <i>Syringa</i> species. Furthermore, the neighbor-joining (NJ) tree based on <i>ITS2</i> + <i>psbA-trnH</i> + <i>trnL-trnF</i> clustered each of the nine <i>Syringa</i> species into distinct clades.</p><p><strong>Discussion: </strong>The study ultimately selected the barcode <i>ITS2</i> + <i>psbA-trnH</i> + <i>trnL-trnF</i>, with an identification rate of 93.6%, as the optimal barcode for identifying nine species of <i>Syringa</i> trees. This combination proved to be highly effective in discriminating <i>Syringa</i> species, highlighting the potential of DNA barcoding as a reliable tool for species identification in <i>Syringa</i>. Future research could focus on expanding the sample size and exploring additional genetic markers to further enhance the accuracy and applicability of DNA barcoding in <i>Syringa</i> species identification.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1544062"},"PeriodicalIF":2.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the underlying molecular connections: a bioinformatics approach to link melanoma and Parkinson's disease.","authors":"Limei Zhang, Dailin Li, Xu Zheng, Moli Wu, Qijun Yao, Haoran Chen, Zhiqiang Ye, Bo Yuan","doi":"10.3389/fgene.2025.1526018","DOIUrl":"10.3389/fgene.2025.1526018","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Melanoma, a highly aggressive form of skin cancer, and Parkinson's disease (PD), a progressive neurodegenerative disorder, have been epidemiologically linked, showing a positive association that suggests a shared etiology. This association implies that individuals with one condition may have an increased risk of developing the other. However, the specific molecular mechanisms underlying this relationship remain unclear. This study aimed to elucidate the molecular mechanisms by conducting a comprehensive comparative analysis of gene expression profiles in both PD and melanoma to identify common differentially expressed genes (DEGs) that may contribute to the pathophysiological overlap between these two conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We analyzed two independent publicly available genomic datasets to identify overlapping DEGs associated with both PD and melanoma. Regulatory networks, including transcription factors (TFs), DEGs, and microRNAs (miRNAs), were constructed. Protein-protein interaction (PPI) networks were established to identify hub genes. Additionally, we investigated the interplay between PD, melanoma, and immune cell infiltration to uncover potential correlations between the expression levels of hub genes and specific subsets of immune cells. Molecular docking studies were performed to identify potential therapeutic agents targeting the DEGs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 41 overlapping DEGs were identified, including VSNL1, ATP6V1G2, and DNM1, which were significantly down-regulated in both PD and melanoma patients. These genes play critical roles in biological processes, cellular components, and molecular functions relevant to the pathogenesis of both diseases. VSNL1 is associated with synaptic vesicle fusion and may impact neuronal communication compromised in PD. ATP6V1G2, a subunit of the V-ATPase, is involved in the dysregulated pH homeostasis observed in melanoma. DNM1, a key player in vesicle trafficking, may influence aberrant cellular transport processes in both diseases. Regulatory and PPI networks revealed potential hub genes and their interactions. Molecular docking studies identified retinoic acid as a potential therapeutic agent targeting VSNL1, ATP6V1G2, and DNM1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Our study provides insights into the shared molecular characteristics of PD and melanoma, identifying potential biomarkers for early diagnosis and prognosis and revealing new therapeutic targets. The discovery of retinoic acid as a promising therapeutic agent represents a significant step forward in drug development and treatment strategies for these diseases. This comprehensive analysis enhances our understanding of the intricate molecular mechanisms underlying the association between PD and melanoma, paving the way for further research and therapeutic advancements. The findings hold the promise of improved diagnosis, prognosis, and personalized treatment strategies","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1526018"},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00461 SNPs rs933647 and rs201864123 modify the risk of adenoid hypertrophy susceptibility for children in South China.","authors":"Chao Hou, Xilian Luo, Xin Wan, Kaining Chen, Zhongren Xian, Kaixiong Xu, Yingjia Zeng, Chenlu Wang, Wan Yang, Zilin Zheng, Yueling Lin, Zhaojin Lu, Yanqiu Chen, Di Che, Xiaoqiong Gu","doi":"10.3389/fgene.2025.1509053","DOIUrl":"10.3389/fgene.2025.1509053","url":null,"abstract":"<p><strong>Background: </strong>Adenoidal hypertrophy (AH) is commonly observed in childhood and closely linked to obstructive sleep apnea (OSA). Despite the high prevalence of AH, its pathophysiological mechanisms remain incompletely understood. We attempt to explore this issue from a genetic perspective. Elevated levels of LINC00461 have been identified in OSA tissues. We aimed to explore the relationship between susceptibility to adenoid hypertrophy and LINC00461 gene polymorphisms.</p><p><strong>Methods: </strong>We genotyped the LINC00461 single nucleotide polymorphisms (SNPs) rs933647 and rs201864123 in 546 AH patients and 574 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between the SNPs and AH risk. The SIPI (Susceptible-Infected-Protected-Infected) method was utilized to analyze SNP-SNP interactions between rs933647 and rs201864123.</p><p><strong>Results: </strong>Our study found that the rs933647 GA polymorphism was associated with an increased risk of AH. Similarly, the T allele of SNP rs201864123 increased AH risk in southern Chinese children. Furthermore, SIPI analysis demonstrated an interaction between these SNPs associated with adenoid hypertrophy risk.</p><p><strong>Conclusion: </strong>The LINC00461 rs933647 GA genotype and rs201864123 T variant may contribute to the susceptibility of AH in the child population of China.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1509053"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of non-coding RNA-mediated endothelial cell-specific regulatory circuits in coronary artery disease risk.","authors":"Boshui Huang, Zhijie Lai, Xiaoyu Wang, Qinhao Zhang, Tingting Hu, Fulong Yu, Shuxian Zhou, Yan Zhang, Juan Meng","doi":"10.3389/fgene.2025.1559798","DOIUrl":"10.3389/fgene.2025.1559798","url":null,"abstract":"<p><p>Coronary artery disease (CAD) remains the leading cause of mortality worldwide, driven by both lifestyle factors and genetic predisposition. Large-scale population genetic studies have greatly enhanced our understanding of the genetic underpinnings of CAD and facilitated the discovery of disease-associated genes. Noncoding RNAs, such as circular RNAs (circRNAs) and microRNAs (miRNAs), play crucial roles in the regulation of these genes. However, the impact of CAD-associated genetic variants on noncoding RNAs and their regulatory gene networks remain largely unexplored. In this study, we systematically identified the targets of both noncoding and coding genes influenced by CAD-associated variants. We constructed a CAD risk gene network, encompassing circRNAs, miRNA and genes, based on the concept of competing endogenous RNA regulation. Additionally, we focused on the endothelial cell (EC)-specific gene regulatory network to prioritize disease-associated circRNAs. Notably, we identified two CAD-associated variants that may disrupt circZNF609 and circABCC1, potentially altering their function as miRNA sponges and impacting EC-specific gene regulation, ultimately contributing to disease risk. Our findings link CAD genetic predisposition to noncoding RNA-mediated gene regulatory mechanisms in specific cell types, providing a valuable resource for novel target identification and advancing precision medicine in CAD.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1559798"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of cfDNA landscape in NIPT and clinical utilities of cfDNA based gene expression inference in prenatal diagnostics.","authors":"Ruo Jia, Jianjiang Zhu, Feng Zhang, Yangbo Sun, Bin Zhang, Yang Du, Hong Qi","doi":"10.3389/fgene.2025.1527884","DOIUrl":"10.3389/fgene.2025.1527884","url":null,"abstract":"<p><p>Cell-free DNA (cfDNA) is a dynamic biomarker reflecting the physiological state of the body. Its unique physical and biochemical properties, inherited from the tissue of origin, enable a wide range of clinical applications. From methylation patterns and fragmentation profiles to genetic variants, cfDNA holds immense potential for diagnosing and monitoring various diseases, including cancer. In this study, we leverage a large collection of non-invasive prenatal testing (NIPT) dataset to explore the genomic landscape of fetal cfDNA, aiming to identify novel biomarkers associated with fetal development and maternal-fetal complications. Our study identifies novel fetal-specific genomic regions, further demonstrating the potential of cfDNA as a versatile biomarker. The prediction model achieved a 100% (12 of 12) positive predictive value (PPV) for hypothyroidism. Whereas for preeclampsia the PPV is much lower (25%, 3 of 12). By establishing a foundation for early hypothyroidism prediction and preeclampsia, we contribute to the expanding applications of NIPT. This approach can be adapted to explore other complex phenotypes and inform biomarker discovery, ultimately advancing maternal-fetal medicine.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1527884"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Integrative genetics and multi-omics of complex human disorders.","authors":"Hongsheng Gui, Christopher J Lessard, Jinhui Liu, Miaoxin Li, Indra Adrianto","doi":"10.3389/fgene.2025.1574431","DOIUrl":"10.3389/fgene.2025.1574431","url":null,"abstract":"","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1574431"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive systematic review and meta-analysis of the TGF-β1 T869C gene polymorphism and autoimmune disease susceptibility.","authors":"Yawen Zhu, Ai Qian, Yuanyuan Cheng, Ming Li, Chuanbing Huang","doi":"10.3389/fgene.2025.1502921","DOIUrl":"10.3389/fgene.2025.1502921","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune diseases (ADs) result from an aberrant immune response, in which the body mistakenly targets its own tissues. The association between TGF-β1 gene polymorphisms and risk of developing autoimmune diseases remains to be established. This meta-analysis aimed to reassess the relationship between TGF-β1 T869C gene polymorphisms and susceptibility to autoimmune diseases.</p><p><strong>Methods: </strong>We conducted a comprehensive search of seven electronic databases for case-control studies investigating the TGF-β1 T869C polymorphism in relation to autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, and juvenile idiopathic arthritis. The search encompassed publications published up to June 2024. Studies were categorized by ethnicity into three groups: Asian, Caucasian, and mixed-ethnicity groups. Five different genetic models were assessed, and the quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using Stata 14.0, by calculating the odds ratio (OR) and 95% confidence interval (CI).</p><p><strong>Results: </strong>A total of 32 case-control studies (31 articles), comprising 4,304 cases and 4,664 controls, were included in this meta-analysis. The overall analysis indicated no significant association between TGF-β1 T869C gene polymorphism and susceptibility to autoimmune diseases. However, subgroup analyses based on race and disease status revealed significant associations. Ethnic subgroup analysis showed that the TGF-β1 T869C allele model (T vs C: OR = 1.422, 95% CI = 1.109-1.824, P = 0.006), homozygous model (TT vs CC: OR = 1.923, 95% CI = 1.232-3.004, P = 0.004), and dominant model (TT + TC vs CC: OR = 1.599, 95% CI = 1.164-2.196, P = 0.004) were associated with autoimmune disease susceptibility in Asians. In the disease subgroup analysis, the results showed that the TGF-β1 T869C allele model (T vs C: OR = 1.468, 95% CI = 1.210-1.781, P = 0.000), recessive model (TT vs TC + CC: OR = 1.418, 95% CI = 1.097-1.832, P = 0.008), dominant model (TT + TC vs CC: OR = 1.747, 95% CI = 1.330-2.295, P = 0.000), homozygous model (TT vs CC: OR = 1.937, 95% CI = 1.373-2.734, P = 0.000), and heterozygous model (TC vs CC: OR = 1.555, 95% CI = 1.199-2.016, P = 0.001) were associated with rheumatoid arthritis susceptibility.</p><p><strong>Conclusion: </strong>The findings of this meta-analysis suggest that carrying the T allele of the TGF-β1 T869C polymorphism increases the risk of autoimmune diseases in Asian populations. Moreover, individuals carrying the T allele are at higher risk of developing rheumatoid arthritis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1502921"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calculating maternal polygenic risk scores from prenatal screening by cell-free DNA data.","authors":"Victoria Corey, Mauro Chavez, Layla Qasim, Tevfik U Dincer, Angela Henry, Salome Bagayan, Sasha Treadup, Mike Mehan, Eileen de Feo, Sung Kim","doi":"10.3389/fgene.2025.1495604","DOIUrl":"10.3389/fgene.2025.1495604","url":null,"abstract":"<p><p>Polygenic Risk Scores (PRS) have enabled quantification of genetic risk for many common and complex traits. Here we developed a novel method to estimate maternal PRS using low-coverage whole genome sequencing data from prenatal screening by cell-free DNA data intended to screen for fetal chromosomal aneuploidies. A prospective study was conducted where 455 consented patients that performed prenatal screening by cell-free DNA as part of their standard of care were randomly selected. Cell-free DNA and genomic DNA were isolated from the plasma and buffy coat of the blood drawn from pregnant women, respectively. Cell-free DNA was sequenced at ∼0.25x coverage while genomic DNA was sequenced at ∼15x coverage. The sequence data was used to impute genotypes which were then used to calculate PRS for paired comparisons. There was a high correlation (average = ∼0.9 across different PRS panels and panel sizes) between PRS from prenatal screening by cfDNA data and PRS from genome sequence data of the buffy coat. This proof-of-concept study illustrates that maternal PRS can be calculated using low-coverage prenatal screening by cfDNA sequence data with high accuracy.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1495604"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput microRNA sequencing in the developing branchial arches suggests miR-92b-3p regulation of a cardiovascular gene network.","authors":"Sian Goldsworthy, Marta Losa, Nicoletta Bobola, Sam Griffiths-Jones","doi":"10.3389/fgene.2025.1514925","DOIUrl":"10.3389/fgene.2025.1514925","url":null,"abstract":"<p><p>Vertebrate branchial arches (BAs) are a developmental paradigm, undergoing coordinated differentiation and morphogenesis to form various adult derivative tissues. MicroRNAs can strengthen gene regulatory networks (GRNs) to promote developmental stability. To investigate microRNA-mediated regulation in BA development, we generated a novel microRNA-sequencing dataset from mouse BAs. We identified 550 expressed microRNAs, of which approximately 20% demonstrate significant differential expression across BA domains. The three most posterior BAs and the connecting outflow tract (PBA/OFT) express genes important for cardiovascular development. We predicted microRNA-target interactions with PBA/OFT-expressed cardiovascular genes and found target sites for miR-92b-3p to be enriched. We used a dual luciferase assay to validate miR-92b-3p interactions with two transcripts encoding the fundamental cardiac transcription factors (TFs), <i>Gata6</i> and <i>Tbx20</i>. Furthermore, we demonstrated that miR-92b-3p mimic can downregulate endogenous <i>GATA6</i> and <i>TBX20</i> in human embryonic stem cells (hESCs) undergoing cardiomyocyte differentiation, confirming microRNA-target binding can occur in a cardiac cell type. miR-92b-3p has previously been shown to target transcripts encoding for two other cardiac TFs, <i>Hand2</i> and <i>Mef2D.</i> Therefore, we hypothesise that miR-92b-3p acts to stabilise cardiovascular GRNs during PBA/OFT development, through multiple microRNA-mediated regulatory networks.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1514925"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}