Search Results (83)

Enhancing wood properties, particularly fiber length (FL), represents a critical objective in Populus tomentosa breeding programs. However, the molecular mechanisms regulating these traits remain largely elusive. Here, an integrative analysis of the PtomiR171 family, uncovering substantial functional divergence among PtomiR171 family members and identified a PtomiR171a-PtoGRAS50 regulatory axis that may control cellulose-related gene expression and influence fiber development in P. tomentosa. Single-nucleotide polymorphism (SNP)-based association studies implicated the role of the PtomiR171a-PtoGRAS50 module in modulating FL. Combined with dual-luciferase reporter gene assay, real-time reverse transcription polymerase chain reaction (RT-qPCR), transcriptome and degradome analysis, PtomiR171a exerts a negative regulatory effect on PtoGRAS50, which is a key regulator of early xylem development. DNA affinity purification sequencing (DAP-seq) identified two downstream putative target genes of PtoGRAS50, both of which are involved in cellulose biosynthesis and metabolism. Unlike previous studies about miRNAs in P. tomentosa, this work narrows its scope to miR171 and elucidates the downstream regulatory module. Collectively, these findings elucidate a critical PtomiR171a-PtoGRAS50 regulatory axis, advancing our understanding of the genetic networks that orchestrate wood properties, deepening insights into FL modulation, and laying a foundation for the development of targeted genetic strategies to enhance wood quality in P. tomentosa. Full article

Background: Loneliness (LON) is a heritable psychosocial trait that frequently co-occurs with major depressive disorder (MDD) and sleep traits. Despite known genetic contributions, the shared genetic architecture and molecular mechanisms underlying their co-occurrence remain largely unknown. This study aimed to uncover novel genetic risk loci and cross-trait gene expression effects. Methods: Large-scale genome-wide association study (GWAS) datasets were analyzed using the causal mixture model (MiXeR) to estimate polygenicity and shared genetic architecture. Genetic correlation analyses were performed using linkage disequilibrium score regression (LDSC) and local analysis of [co]variant annotation (LAVA). Conditional and conjunctional FDR methods further identified single nucleotide polymorphisms (SNPs). FUMA was used for gene mapping and annotation, and transcriptome-wide association studies (TWAS) assessed cross-trait gene expression effects. Results: Analyses revealed extensive polygenic overlap between LON, MDD, and sleep-related traits, with concordant and discordant effects. Several novel loci were identified, and cross-trait gene expression effects were observed in multiple brain-expressed genes, including WNT3, ARHGAP27, PLEKHM1, and FOXP2. These findings provide insight into the shared genetic architecture and relevance of these traits. Conclusions: This study demonstrates a significant shared polygenic architecture among LON, MDD, and sleep traits, providing new biological insights. It advances our understanding of cross-trait genetic mechanisms and identifies potential targets for future research, offering broader implications for trait co-occurrence. Full article

Background: The ESR2 gene encodes Estrogen Receptor-β1 (ERβ1), a putative tumor suppressor in hormone-dependent malignancies. Although ERβ biology has been studied extensively at the expression level, the functional impact of nonsynonymous SNPs (nsSNPs) and untranslated-region (UTR) variants in ESR2 remains underexplored. Methods: We retrieved variants from Ensembl and performed an integrative in silico assessment using PredictSNP, I-Mutant, MUpro, HOPE, MutPred2, and CScape for pathogenicity, oncogenicity and structural stability; STRING/KEGG/GO for pathway context; RegulomeDB and polymiRTS for regulatory effects; and cBioPortal for pan-cancer clinical outcomes (breast (BRCA), endometrial (UCEC), and ovarian (OV)). We evaluated effects of nsSNPs on ERβ1 stability, ligand-binding/DNA-binding domains, co-factor recruitment, and post-transcriptional regulation. Results: Across tools, 93 missense nsSNPs were consistently predicted to be deleterious. Notably, several variants were found to destabilize ERβ1, particularly within the ligand-binding domains (LBD) and DNA-binding domains (DBD). Putative oncogenic drivers R198P and D154N showed high CScape scores and very low population frequencies, consistent with pathogenicity. Several substitutions were predicted to impair coactivator binding and disrupt interactions with key transcriptional partners, including JUN, NCOA1, and SP1. At the post-transcriptional level, rs139004885 was predicted to disrupt miRNA binding, while 3′UTR rs4986938 showed strong regulatory potential and comparatively high population frequency; by contrast, most other identified SNPs were rare. Clinically, pan-cancer survival analyses indicated worse overall survival (OS) in BRCA for ESR2-Altered cases (HR ≈ 2.25; q < 0.001), but better OS in UCEC (HR ≈ 0.24; q ≈ 0.014) and OV (HR ≈ 0.29; q < 0.001), highlighting a tumor-type-specific association. Conclusions: This integrative analysis prioritizes high-impact ESR2 variants that likely impair ERβ1 structure and shows context-dependent clinical effects. Despite their generally low frequency (except for rs4986938), prospective validation linking variant class to ERβ expression and survival outcomes is needed to support biomarker development and therapeutic applications. Full article

The aim was to investigate the genetic effects of a SNP located in the precursor region of gga-miR-3528. (1) Single-nucleotide polymorphisms within precursor regions of microRNAs play crucial biological roles. (2) Utilizing a Gushi–Anka F₂ resource population (n = 860), we screened and validated miRNA SNPs. A SNP mutation in the miR-3528 precursor region was identified. Specific primers were designed to amplify the polymorphic fragment. Genotyping was performed for this individual SNP across the population, using the MassArray system. Association analyses were conducted between this SNP and chicken growth and body measurement traits, carcass traits, meat quality traits, and serum enzyme activities. (3) The rs14098602 (+12 bp A > G) was identified within the precursor region of gga-miR-3528. Significant associations (p < 0.05) were observed between this SNP and chicken growth traits (body weight at the age of 0 day, body weight at the age of 2 weeks, and body weight at the age of 4 weeks), carcass traits (evisceration weight), meat quality traits (subcutaneous fat rate and pectoral muscle density), and serum enzyme activities (total protein, albumin, globulin, cholinesterase, and lactate dehydrogenase). (4) These findings suggest that the polymorphism at rs14098602 may influence chicken growth, meat quality, and serum biochemical indices, through specific mechanisms. The gga-miR-3528 gene likely plays an important role in chicken development. Therefore, this SNP can serve as a molecular marker for genetic breeding and auxiliary selection of growth-related traits, facilitating the rapid establishment of elite chicken populations with superior genetic resources. Full article

Background/Objectives: MicroRNAs (miRNAs) are molecules involved in biological regulation processes, including type 2 diabetes and its complications development. Single nucleotide polymorphisms (SNPs) can alter miRNA mechanisms, resulting in loss or gain effects. VEGFA is recognized for its role in angiogenesis. However, its overexpression can lead to deleterious effects, such as disorganized and inefficient vasculature. Under hyperglycemic conditions, VEGFA expression seems to increase, which may contribute to the development of microvascular and macrovascular diabetic complications. Several miRNAs are associated with VEGFA regulation and seem to act in the prevention of dysregulated expression. This study aimed to investigate SNPs in miRNA regions related to the loss effect in VEGFA regulation, examining their frequency and potential physiological effects in the development of diabetic complications. Methods: VEGFA-targeting miRNAs were identified using the R package multimiR, with validated and predicted results. Tissue expression analysis and SNP search were data-mined with Python 3 for miRNASNP-v3 SNP raw databases. Allele frequencies were obtained from dbSNP. The miRNA–mRNA interaction comparison was obtained in the miRmap tool through Python 3. MalaCards were used to infer physiological disease association. Results: The variant rs371699284 was selected in hsa-miR-654-3p among 103 potential VEGFA-targeting miRNAs. This selected SNP demonstrated promising results in bioinformatics predictions, tissue-specific expression, and population frequency, highlighting its potential role in miRNA regulation and the resulting loss in VEGFA-silencing efficiency. Conclusions: Our findings suggest that carriers of rs1238947970 may increase susceptibility to diabetic microvascular and macrovascular complications. Furthermore, in vitro and in silico studies are necessary to better understand these processes. Full article

Background: In Staphylococcus aureus, antimicrobial resistance (AMR) imposes significant fitness costs (FCs), including reduced growth rate, interbacterial competitiveness, and virulence. However, the FC molecular basis remains poorly understood. This study investigated the FC omic basis and compensatory adaptations in high-risk HA-, LA-, and CA-MRSA, acquiring mono- or cross-resistance to second-line daptomycin (DAP) and dalbavancin (DAL), as well as reduced susceptibility (RS) to first-line glycopeptides, i.e., vancomycin and teicoplanin (GLYs, i.e., VAN, TEC), related to the specific mechanism of action (MOA)-related AMR-mechanisms and genomic backgrounds, paying increasing FCs. Methods: The FC omic basis associated with mono- or cross- DAP-/DAL-R and GLY-RS were investigated by integrated omics. This study focused on core-genome essential (EG) and accessory virulence gene (VG) SNPomics and transcriptomics by Illumina MiSeq whole-genome sequencing, RNA-seq, and bioinformatic analysis. Results: Moderate impact nsSNPs were identified in EGs related to vital cellular functions and VGs. Comparative EG transcriptomics revealed differential expressions and key dysregulations—via asRNAs—prevalently affecting the protein synthesis and cell-envelope EG clusters, as well as the VG cluster. Conclusions: Our data, firstly, underlined the EG and VG mutation- and transcription-driven omic-based FC burden and the compensatory adaptations associated with the emergence of mono-DAP-R, cross-DAP-R/hGISA, and DAP-R/DAL-R/GISA, linked to specific MOA-related AMR-mechanisms and genomic backgrounds in high-risk HA-, LA-, and CA-MRSA. Full article

Background: Single-nucleotide polymorphisms (SNPs) are associated with multiple disorders and various cancer types. In the context of cancer, alterations within non-coding regions, specifically 3′ untranslated regions (3′ UTR), have proven substantially important. Methods: In this study, we utilized various bioinformatics tools to examine the effect of SNPs in the 3′ UTR. We retrieved the 3′ UTR SNPs of the Signal Transducer and Activator of Transcription 1 (STAT1) gene from the National Centre for Biotechnology Information (NCBI) website. Next, we employed the Polymorphism in miRNAs and their corresponding target sites (PolymiRTS) database to predict the 3′ UTR SNPs that create new microRNA (miRNA) binding sites and their respective miRNAs. The effect of the 3′ UTR SNPs on the messenger RNA structure was studied using RNAfold server. We used Cscape tool to predict the oncogenic 3′ UTR SNPs. Then, we submitted the miRNAs to the miRNet database to visualize the miRNA-miRNAs’ target genes interaction, for which gene enrichment analysis was performed using ShinyGO. Protein–protein interactions were conducted using the STRING database. We conducted miRNA enrichment analysis utilizing miRPathDB, subsequently performing miRNA differential expression analysis through oncoMIR, and the StarBase database. The survival analysis of the upregulated miRNAs in cancer was investigated using the Kaplan–Meier Plotter. Result: Twelve SNPs were predicted to create new miRNA binding sites. Two of them, rs188557905 and rs190542524, were predicted to destabilize the mRNA structures. We predicted rs190542524, rs11305, rs186033487, and rs188557905 to be oncogenic 3′ UTR SNPs, with high-confidence predictions and scores > 0.5. Using miRNAs’ target genes enrichment analysis, this study indicated that the miRNA target genes were more likely to be involved in cancer-related pathways. Our comprehensive analysis of miRNAs, their functional enrichment, their expression in various types of cancer, and the correlation between miRNA expression and survival outcome yielded these results. Our research shows that the oncogenic 3′ UTR SNP rs190542524 creates a new binding site for the oncogenic miRNA hsa-miR-136-5p. This miRNA is significantly upregulated in BLCA, LUSC, and STAD and is linked to poor survival. Additionally, rs114360225 creates a new binding site for hsa-miR-362-3p, influencing LIHC. Conclusions: These analyses suggest that these 3′ UTR SNPs may have a functional impact on the STAT1 gene’s regulation through their predicted effect on miRNA binding sites. Future experimental validation could establish their potential role in the diagnosis and treatment of various diseases, including cancer. Full article

Breast cancer (BC) is the most common malignant disease in women worldwide. Several studies have reported that microRNA-146a (miR-146a) dysregulation plays a role in multiple cancers, including BC. However, the mechanism underlying this association is controversial, possibly reflecting diverse roles for this miR in different types of cancer. The SNP rs2910164:G>C, located within the miR-146a precursor, has been linked to a BC risk. Our group previously showed a specific association between rs2910164:G>C and an increased BC risk in patients with early-onset sporadic BC. There are no studies in the literature that evaluate the functional consequences of the rs2910164 polymorphism in the BC process. Therefore, the goal of the present study was to evaluate in vitro the effect of the SNP rs2910164:G>C on BC progression in luminal A and triple-negative cell lines. We found that rs2910164:G>C upregulated the expression of two mature miR-146a sequences, 3p and 5p. Furthermore, pre-miR-146a-C enhanced proliferation, migration, and invasion in luminal A and triple-negative breast cells, as well as decreasing cisplatin-induced apoptosis. Interestingly, the pre-miR-146a C allele decreased cisplatin resistance in MCF-7 cells but increased cisplatin resistance in MDA-MB-231 cells. We propose that the rs2910164 C allele promotes miR-146a overexpression, which is causally involved in proliferation, migration, invasion, apoptosis, and cisplatin resistance. Full article

Background: ZDHHC19—a protein acyltransferase—is known to be induced in sepsis, a dysregulated immune response to infection, but the underlying molecular mechanisms remain elusive. In this study, we aimed to explore whether upregulation of ZDHHC19 is modulated by single nucleotide polymorphisms (SNPs) affecting the binding of microRNA in the 3’ untranslated region of the gene. Methods: Inpatients with clinically verified severe infection (n = 83) or sepsis (n = 63) were recruited to the study. Genomic DNA and total RNA were prepared from buccal and peripheral blood samples, respectively. Genotyping of rs112579116 and rs2293161 SNPs was performed by TaqMan real-time PCR assays, while ZDHHC19 mRNA as well as miR-4733 and -596 microRNA levels were quantitated by reverse transcription qPCR. Correlations between genotypes, expression levels and clinical parameters were assessed by the Shapiro–Wilk, Mann–Whitney and t-tests. Results: Transcript levels of ZDHHC19 were significantly enhanced in septic blood samples (p = 0.0000709) and associated with clinical parameters such as procalcitonin levels, blood cell counts and clotting factors. Levels of both miRNAs showed an inverse but not significant correlation with those of ZDHHC19. Conclusions: Expression of ZDHHC19 should be considered a reliable molecular marker of sepsis, but further investigations are needed to shed light on regulatory mechanisms involved. Full article

Tail fat is essential for sheep survival in extreme environments, yet its significance is often overlooked, leading to the decline of fat-tailed breeds. This study identified a novel lncRNA, lncRSFD1 (TCONS_00054953), through transcriptome sequencing, showing differential expression in the tail adipose tissues of Lanzhou Fat-Tailed (LFT) sheep and Tibetan (TS) sheep. Highly expressed in adipose tissues, lncRSFD1 inhibits preadipocyte proliferation and promotes 3T3-L1 differentiation, suggesting its role in regulating fat deposition. Located in both the cytoplasm and nucleus, lncRSFD1 targets the neighboring gene PDE4DIP and may function as a molecular sponge for conserved miRNAs, including oar-miR-30a-3p, oar-miR-329b-5p, and oar-miR-431, which are known to influence fat and muscle-related physiological processes. Moreover, the core promoter of lncRSFD1 (−2607 bp to −1776 bp) harbors four SNPs (g.-2429G>A, g.-2030T>C, g.-2016C>T, g.-2015G>A) significantly associated with growth traits such as body height in Guiqian Semi-Fine Wool (GSFW) sheep. These findings suggest lncRSFD1 plays a key role in fat deposition and growth regulation, offering new insights into the molecular mechanisms of lncRNAs in sheep. It provides a potential target for genetic improvement and molecular breeding to enhance fat deposition and adaptability in sheep breeds. Full article

Colorectal cancer (CRC) is the third most common neoplasm in the world and the second with the highest mortality rate. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes known as mirSNPs may be related to dysregulated miRNA expression in several neoplasms. This systematic review aims to investigate studies that investigate SNPs located in regions of miRNA genes that influence their expression and are associated with CRC, as well as their potential as biomarkers for the disease, based on the available literature. For this, searches were performed in public databases, including MEDLINE/PubMed, Embase, Web of Science, and Scopus. The rigorous review of the PRISMA 2020 guidelines and the methodological quality of these studies was assessed using the Newcastle–Ottawa scale and the Mixed Methods Assessment Tool. Of the 175 studies identified, 26 were considered eligible: 18 of them highlighted mirSNPs as potential biomarkers of risk and prognosis for CRC; 4 studies suggested a protective role; 1 study linked mirSNPs to treatment; 3 studies found no relevant evidence. These results highlight the importance of conducting further research on the topic, given the potential of these biomarkers to contribute to risk assessment, prognosis, and the development of therapeutic strategies for patients with CRC. Full article

Benzene, toluene, and xylene (BTX) co-exist in human environments, yet their individual and combined effects on genetic damage at low exposure levels are not fully understood. Additionally, single nucleotide polymorphisms in microRNAs (mirSNPs) might be involved in cancer etiology by affecting the related early health damage. To investigate the influence of BTX exposure, mirSNPs, and their interactions on genetic damage, we conducted a cross-sectional study in 1083 Chinese petrochemical workers, quantifying the BTX cumulative exposure levels and multiple genetic damage biomarkers. Additionally, we genotyped multiple common mirSNPs. Benzene and a BTX mixture were positive associated with the olive tail moment (OTM) and tail DNA% (p < 0.05). Higher levels of toluene and xylene enhanced the association of benzene with genetic damage levels. Genotypes and/or mutant allele counts of miR-4482-related rs11191980, miR-4433-related rs136547, miR-27a-related rs2594716, miR-3130-related rs725980, and miR-3928-related rs878718 might significantly influence genetic damage levels. Stronger effect estimates of benzene/BTX exposure were found in carriers of miR-196a-2-related rs11614913 heterozygotes and of wild homozygotes of miR-1269b-related rs12451747, miR-612-related rs12803915, and miR-4804-related rs266437. Our findings provide further support of the involvement of BTX co-exposure, mirSNPs, and their gene–environment interactions in determining the severity of DNA strand break in a complex manner. Full article

The purpose of this prospective case–control study is to investigate the correlation of the miR-143 gene rs353292 polymorphism in Caucasian women with recurrent pregnancy loss (RPL) compared to a matched control group with at least one live birth and without pregnancy losses. In total, 110 women with recurrent pregnancy losses and 95 control women were recruited. Peripheral blood was collected from all women, and the isolation of DNA was performed with Monarch Genomic DNA Purification. Polymerase chain reaction was applied to amplify the DNA sequence of the miR-143 gene promoter, carrying the polymorphism rs353292. The incidence of genotype CC in the RPL group was statistically significantly higher than in control group (p < 0.0001). Allele C (CT + CC) in the control group was found in 47.36%, and in the RPL group was found in 68.17% (p = 0.006). SNP rs353292 T>C was associated with increased risk of recurrent pregnancy loss. The calculated odds ratio for CT + CC vs. TT and for CC vs. TT were significant higher (p = 0.0028 and p < 0.0001, respectively). The study results suggest that the rs353292 polymorphism is associated with a statistically significant increase in RPL prevalence. The present study provides additional evidence in favor of a shared pathophysiological mechanism that contributes to both RPLs, potentially through inflammatory processes and epithelial–mesenchymal transition dysregulation. Full article

In view of the predicted significant increase in global meat production, alternative sources such as horsemeat are becoming increasingly important due to their lower environmental impact and high nutritional value. This study aimed to identify SNP markers on the GeneSeek^® Genomic Profiler™ Equine (Neogen, Lansing, MI, USA) that are important for horsemeat production traits. First, orthologous genes related to meat yield in cattle and common genes between horses and cattle within QTLs for body size and weight were identified. Markers for these genes were then evaluated based on predicted variant consequences, GERP scores, and positions within constrained elements and orthologous regulatory regions in pigs. A total of 268 markers in 57 genes related to meat production were analyzed. This resulted in 27 prioritized SNP markers in 22 genes, including notable markers in LCORL, LASP1, IGF1R, and MSTN. These results will benefit smallholder farmers by providing genetic insights for selective breeding that could improve meat yield. This study also supports future large-scale genetic analyses such as GWAS and Genomic Best Linear Unbiased Prediction (GBLUP). The results of this study may be helpful in improving the accuracy of genomic breeding values. However, limitations include reliance on bioinformatics without experimental validation. Future research can validate these markers and consider a wider range of traits to ensure accuracy in equine breeding. Full article

The expression of inflamma-miRs and human leukocyte antigen (HLA) haplotypes could indicate mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We used international databases to conduct a systematic review of studies on HLA variants and a meta-analysis of research on microRNAs (miRNAs). We aimed to analyze the discriminative value of HLA variants and miRNAs in MCI, AD and controls to evaluate the protective or causative effect of HLA in cognitive decline, establish the role of miRNAs as biomarkers for the early detection of AD, and find a possible link between miRNAs and HLA. Statistical analysis was conducted using Comprehensive Meta-analysis software, version 2.2.050 (Biostat Inc., Englewood, NJ, USA). The effect sizes were estimated by the logarithm base 2 of the fold change. The systematic review revealed that some HLA variants, such as HLA-B*4402, HLA-A*33:01, HLA-A*33:01, HLA-DPB1, HLA-DR15, HLA-DQB1*03:03, HLA-DQB1*06:01, HLA-DQB1*03:01, SNPs on HLA-DRB1/DQB1, and HLA-DQA1, predisposed to cognitive decline before the occurrence of AD, while HLA-A1*01, HLA-DRB1∗13:02, HLA-DRB1*04:04, and HLA-DRB1*04:01 demonstrated a protective role. The meta-analysis identified let-7 and miR-15/16 as biomarkers for the early detection of AD. The association between these two miRNA families and the HLA variants that predispose to AD could be used for the early screening and prevention of MCI. Full article