Search Results (621)

Transcription factors play crucial roles in regulating gene expression, and any dysregulation in their levels could be involved in cancer progression. The role of androgen receptors (AR) and zinc finger (ZNF) proteins in tumors, like prostate cancer (PC), remains poorly understood. Moreover, due to the multifaceted transcriptional behavior of ARs and ZNFs, their biological role in cancer progression may also depend on the interplay with micro-RNAs (miRNAs). Based on The Cancer Genome Atlas (TCGA) database, we analyzed the expression levels of zinc finger transcripts and ARs in PC. Specifically, exploring their involvement in cancer progression and regulation by miRNAs. The analysis relied on several tools to create a multivariate combination of the original biomarkers to improve their diagnostic efficacy. Multidimensional Scaling (MDS) identified two new dimensions that were entered into a regression analysis to determine the best predictors of overall survival (OS) and disease-free interval (DFI). A combination of both dimensions predicted almost 50% (R² = 0.46) of the original variance of OS. Kaplan–Meier survival analysis also confirmed the significance of these two dimensions regarding the clinical output. This study showed preliminary evidence that several transcription factor expression levels belonging to the zinc family and related miRNAs can effectively predict patients’ overall PC survivability. Full article

Madagascar harbors a rich marine biodiversity, yet detailed knowledge of its fish species remains limited. Of the 1689 species listed in 2018, only 22% had accessible cytochrome oxidase I (COI) sequences in public databases. In response to growing pressure on fishery resources, this study aims to strengthen biodiversity monitoring tools. Its objectives were to enrich the COI database for Malagasy marine fishes, create the first 12S reference library, and evaluate the taxonomic resolution of different 12S metabarcodes for eDNA analysis, namely MiFish, Teleo1, AcMDB, Ac12S, and 12SF1/R1. An integrated approach combining morphological, molecular, and phylogenetic analyses was applied for specimen identification of fish captured using various types of fishing gear in Toliara and Ranobe Bays from 2018 to 2023. The Malagasy COI database now includes 2146 sequences grouped into 502 Barcode Index Numbers (BINs) from 82 families, with 14 BINs newly added to BOLD (The Barcode of Life Data Systems), and 133 cryptic species. The 12S library comprises 524 sequences representing 446 species from 78 families. Together, the genetic datasets cover 514 species from 84 families, with the most diverse being Labridae, Apogonidae, Gobiidae, Pomacentridae, and Carangidae. However, the two markers show variable taxonomic resolution: 67 species belonging to 35 families were represented solely in the COI dataset, while 10 species from nine families were identified exclusively in the 12S dataset. For 319 species with complete 12S gene sequences associated with COI BINs (Barcode Index Numbers), 12S primer sets were used to evaluate the taxonomic resolution of five 12S metabarcodes. The MiFish marker proved to be the most effective, with an optimal similarity threshold of 98.5%. This study represents a major step forward in documenting and monitoring Madagascar’s marine biodiversity and provides a valuable genetic reference for future environmental DNA (eDNA) applications. Full article

Small non-coding microRNAs (miRNAs) play crucial roles in the degradation of the messenger RNAs (mRNAs) that are involved in various biological processes post-transcriptionally and translationally. Many plants, especially Musa spp. (plantains and bananas), which are important perennial herbs of the family Musaceae, experience significant yield loss due to abiotic stressors, yet only a few miRNAs involved in this response have been identified. This study employed in silico analyses of transcriptome shotgun assembly (TSA) and expressed sequence tag (EST) sequences to identify Musa miRNAs and their target genes. Leaf and root tissues from three Musa genomic groups (AAA, AAB, and ABB) under drought stress were analyzed using quantitative real-time PCR (qRT-PCR) to validate the expression of miRNAs. A total of 17 potential conserved miRNAs from 11 families were identified, with the minimal folding free energies (-kcal/mol) of precursors ranging from −136.00 to −55.70, as observed through RNA folding analysis. Six miRNAs (miR530-5p, miR528-5p, miR482a, miR397a, miR160h, and miR399a) showed distinct tissue-specific expression patterns in the roots and leaves across the three groups. A total of 59 target regulatory transcription factors and enzymes involved in stress response, growth, and metabolism were predicted. Of these, 11 targets were validated for miR530-5p, miR528-5p, miR482a, and miR397a, using qRT-PCR. These four stress-responsive miRNAs exhibited an inverse expression relationship with their target genes across two different tissues in Musa groups. This research provides insights into miRNA-mediated drought stress responsiveness in Musa spp., potentially benefiting future studies on gene regulation under drought stress. Full article

Introduction: The interface between T cells and the tumor microenvironment, termed the ‘immunological synapse’, consists of multiple checkpoint protein pairs co-expressed on both sides of the synapse. mir-16, a microRNA from a widely known tumor-suppressor family of miRNAs, was previously shown by us to be downregulated in melanoma. As other miRNAs from this family have been shown to directly target checkpoint proteins, here we investigated whether miR-16 influences the expression patterns of checkpoint proteins in melanoma. Methods: Single-cell gene expression data from the melanoma microenvironment were retrieved from a public database. Melanoma cell lines were established from metastatic lesions and transiently transfected with an hsa-miR-16-5p-mimic RNA or a mir-16-expressing plasmid. The mRNA expression profiles were analyzed using an Affymetrix microarray. Direct targets of miR-16 were identified by luciferase reporter assays. Protein levels were assessed by Western blotting. Results: Bioinformatic analysis revealed that the expression levels of eight checkpoint mRNAs, known to be present on the melanoma side of the immunological synapse, were highly correlated. Four of these mRNAs contained putative binding sites for the miR-15/16 family. miR-16 expression was significantly reduced in melanoma cells, compared to normal melanocytes. Luciferase reporter assays demonstrated that miR-16 directly targets the 3′ untranslated regions (3′UTRs) of CD40, CD80. The mRNAs downregulated following miR-16 overexpression were highly enriched for genes involved in autophagy, vesicle-mediated transport, and the regulation of protein membrane localization. Among these, VTI1B and SMPD1 were confirmed to be direct targets of miR-16. Transient overexpression of miR-16 resulted in a significant reduction in SMPD1 and VTI1B levels in melanoma cell lines. Conclusions: Our findings suggest that miR-16 potentially modulates melanoma tumorigenesis, metastasis and immunogenicity by altering the composition of checkpoint proteins at the immunological synapse and by regulating cellular pathways associated with intracellular trafficking and transmembrane protein presentation. Full article

T-cadherin (CDH13) is an atypical, glycosyl-phosphatidylinositol-anchored cadherin with functions ranging from axon guidance and vascular patterning to adipokine signaling and cell-fate specification. Originally identified as a homophilic cue for migrating neural crest cells, projecting axons, and growing blood vessels, it later emerged as a dual metabolic receptor for cardioprotective high-molecular-weight adiponectin and atherogenic low-density lipoproteins. We recently showed that mesenchymal stem/stromal cells lacking T-cadherin are predisposed to adipogenesis, underscoring its role in lineage choice. Emerging evidence indicates that CDH13 expression and function are fine-tuned by non-coding RNAs (ncRNAs). MiR-199b-5p, miR-377-3p, miR-23a/27a/24-2, and the miR-142 family directly bind CDH13 3′-UTR or its epigenetic regulators, affecting transcription or accelerating decay. Long non-coding RNAs (lncRNAs), including antisense transcripts CDH13-AS1/AS2, brain-restricted FEDORA, and context-dependent LINC00707 and UPAT, either sponge these miRNAs or recruit DNMT/TET enzymes to the CDH13 promoter. Circular RNAs (circRNAs), i.e.circCDH13 and circ_0000119, can add a third level of complexity by sequestering miRNA repressors or boosting DNMT1. Collectively, this ncRNA circuitry regulates T-cadherin across cardiovascular, metabolic, oncogenic, and neurodegenerative conditions. This review integrates both experimentally validated data and in silico predictions to map the ncRNA-CDH13 crosstalk between health and disease, opening new avenues for biomarker discovery and RNA-based therapeutics. Full article

Chronic inflammation is increasingly recognized as a driver of glioma progression, with tumor necrosis factor-alpha (TNF-α) playing a central role in modulating the tumor microenvironment. This study aimed to investigate the expression profiles and regulatory mechanisms of TNF-α and its downstream mediators—including interleukin-1 beta (IL-1β), Mitogen-Activated Protein Kinase Kinase Kinase 8 (MAP3K8), and Mitogen-activated protein kinase kinase 7 (MAP2K7)—in astrocytic tumors of varying malignancy. We conducted an integrative molecular analysis of 60 human astrocytic tumor samples (20 G2, 12 G3, 28 G4) using transcriptomic microarrays, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR), Enzyme-Linked Immunosorbent Assay (ELISA), Western blotting, immunohistochemistry, methylation-specific PCR, and miRNA profiling. Prognostic associations were evaluated using Kaplan–Meier survival and Cox regression analyses. TNF-α, IL-1β, and MAP3K8 were significantly upregulated in high-grade tumors, with log₂ fold changes ranging from 5.56 to 8.76 (p < 0.001). High expression of TNF-α (HR = 2.10, 95% CI: 1.27–3.46, p = 0.004), IL-1β (HR = 2.35, 95% CI: 1.45–3.82, p = 0.001), and MAP3K8 (Hazard Ratio; HR = 1.88, 95% confidence interval; 95% CI: 1.12–3.16, p = 0.015) was associated with poorer overall survival. miR-34a-3p and miR-30 family members, predicted to target TNF-α and IL-1β, were markedly downregulated in G3/G4 tumors (e.g., miR-30e-3p fold change: –3.78, p < 0.01). Promoter hypomethylation was observed in G3/G4 tumors, supporting epigenetic activation. Our findings establish a multi-layered regulatory mechanism of TNF-α signaling in astrocytic tumors. These data highlight the TNF-α/IL-1β/MAP3K8 axis as a critical driver of glioma aggressiveness and a potential therapeutic target. Full article

Soybean (Glycine max (L.) Merr.) is a critical crop in China, serving as a primary source of food, oil, and animal feed. Drought stress significantly impacts soybean growth and yield. MicroRNAs (miRNAs) play crucial roles in plant drought responses. The miR164 family is highly conserved across plant species and has been shown to participate in drought responses in a range of plants, yet the function of miR164 in soybean remains unclear. In this study, we identified GmNAC35 as a direct target of miR164 through published degradome sequencing data and 5′ RLM-RACE assays. Under drought stress, miR164 members (e.g., MIR164a, MIR164f, and MIR164k) rapidly down-regulated, reaching their lowest expression at 2 h and returning to basal levels within 6 h. Conversely, GmNAC35 showed an inverse pattern, indicating negative regulation by miR164. Overexpression of GmNAC35 enhanced drought tolerance in transgenic soybean plants, as evidenced by higher survival rates and reduced water loss. Transcriptomic analysis revealed that GmNAC35 modulates stress-responsive pathways, including ABA signaling and phenylpropanoid biosynthesis. Our findings indicate that miR164 negatively regulates GmNAC35, a positive regulator of drought tolerance. This enhances our understanding of the molecular mechanisms of drought tolerance in soybean and may inform strategies for breeding drought-resistant varieties. Full article

Drought stress limits plant survival and yield in arid regions. Uncovering the molecular mechanisms of drought tolerance is key to developing resilient crops. This study used Arabidopsis thaliana as a model to perform an in silico analysis of miRNA–mRNA interactions linked to post-transcriptional drought response. Using the MirTarget program, 274 miRNAs and 48,143 gene transcripts were analyzed to predict high-confidence miRNA–mRNA interactions based on binding free energies (−79 to −129 kJ/mole). Predicted binding sites were located in the CDS, 5′UTR, and 3′UTR regions of target mRNAs. Key regulatory interactions included ath-miR398a-c and ath-miR829-5p targeting ROS detoxification genes (CSD1, FSD1); ath-miR393a/b-5p and ath-miR167a-c-5p targeting hormonal signaling genes (TIR1, ARF6); and the miR169 family, ath-miR414, and ath-miR838 targeting drought-related transcription factors (NF-YA5, DREB1A, WRKY40). Notably, ath-miR414, ath-miR838, and the miR854 family showed broad regulatory potential, targeting thousands of genes. These findings suggest the presence of conserved regulatory modules with potential roles in abiotic stress tolerance. While no direct experimental validation was performed, the results from Arabidopsis thaliana provide a useful genomic framework for hypothesis generation and future functional studies in non-model plant species. This work provides a molecular foundation for improving drought and salt stress tolerance through bioinformatics-assisted breeding and genetic research. Full article

Background/Objectives: This study aimed to evaluate the relationship between sirtuin family members (SIRT1, SIRT3, and SIRT6) and Wnt/β-catenin pathways with inflammation during the rejection process following kidney transplantation, as well as to explore their potential roles as candidate biomarkers. Materials and Methods: Blood samples were collected from 35 kidney transplant rejection patients and 30 healthy controls. The gene expression levels of SIRT1, SIRT3, SIRT6, and Wnt/β-catenin pathway components were measured using real-time PCR, and miRNA and lncRNA expression levels were analyzed. Statistical analyses were performed using SPSS version 23. Results: Significant alterations in SIRT1, SIRT3, and SIRT6 expression levels were observed in rejection patients, suggesting their potential role in disease pathogenesis and as therapeutic biomarkers. Key altered genes included hsa-miR-34c-1, hsa-miR-122b-5b, MALAT1, HOTAIR, LINC00473, TUG, PVT1, SIRT1, SIRT3, SIRT6, WNT1, TCF-LEF, LRP, AXIN1, IL1B, IL6, and IFNB1, all showing significant changes. However, no significant differences were found for miRNAs such as hsa-miR-21-2, hsa-miR-155-5p, and hsa-miR-200b-3p. SIRT1 expression was significantly decreased in the cellular rejection group, with a more pronounced reduction in these patients. Significant differences in SIRT1 expression were observed with interstitial inflammation and glomerulitis. Increased inflammation severity correlated with decreased SIRT1 and increased TCF-LEF, TUG, and miR-21 levels, while tubulitis severity was associated with elevated TCF-LEF and miR-155 expression. Conclusions: Along with the activation of Wnt/β-catenin pathways and increased levels of certain miRNAs and long non-coding RNAs (lncRNAs) associated with TCF-LEF transcription factors, the observed decrease in SIRT1 expression may be related to the severity of inflammation and tubulitis. These findings suggest that SIRT1, Wnt/β-catenin pathways, and non-coding RNAs play a role in the rejection process following kidney transplantation and could be considered as potential biomarkers or therapeutic target candidates for future research. Full article

MicroRNAs (miRs) are epigenetic regulators of several metabolic diseases, including gestational diabetes mellitus (GDM). Objectives: Following a systematic review, we propose a pattern of key circulating miRs associated with placental changes and their potential role in the fetus. Methods: A systematic investigation of studies published between January 2011 and July 2024 was conducted in the PubMed, ScienceDirect, Trip Database, and Wiley databases. A total of 90 articles were analyzed. Results: Two hundred twenty-six circulating microRNAs were identified in women with GDM, and fifty miRs were validated by PCR, with miRs-16-5p, -29a-5p, and -195-5p being the most frequently reported. Interestingly, miR-16-5p was also expressed in the placenta but not in umbilical cord blood or amniotic fluid. Conversely, miR-126-3p was expressed in circulation, the placenta, umbilical cord blood, and amniotic fluid. Several reports describe high expression levels of miR-518d in maternal circulation, umbilical cord blood, and placenta. Controversial results regarding the expression of miR-29a-3p, -137, and -148a-3p were identified when comparing umbilical cord blood and the placenta. Conclusions: In silico analyses suggest that the miR-29 family, as well as miRs-16-5p, -126-3p, -195-5p, and -518b, may be involved in alterations in the heart, brain, and kidneys in the embryo when exposed to a hyperglycemic environment. Full article

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular cholestasis due to biallelic variations in the ABCB11 (ATP-binding cassette B11) gene encoding the canalicular bile salt export pump (BSEP). Some missense variants identified in patients with PFIC2 do not traffic properly to the canalicular membrane. However, 4-phenybutyrate (4-PB) has been shown in vitro to partially correct the mis-trafficking of selected variants, resulting in an improvement of the medical conditions of corresponding PFIC2 patients. Herein, we report the ability of 4-PB analogous or homologous drugs and of non-4-PB related chemical correctors to rescue the canalicular expression and the activity of the folding-defective Abcb11^R1128C variant. New compounds, either identified by screening a chemical library or designed by structural homology with 4-PB (or its metabolites) and synthesized, were evaluated in vitro for their ability to (i) correct the canalicular localization of Abcb11^R1128C after transfection in hepatocellular polarized cell lines; (ii) restore the ³H-taurocholate transport of the Abcb11^R1128C protein in Madin–Darby canine kidney (MDCK) cells stably co-expressing Abcb11 and the sodium taurocholate co-transporting polypeptide (Ntcp/Slc10A1). Glycerol phenylbutyrate (GPB), phenylacetate (PA, the active metabolite of 4-PB), 3-hydroxy-2-methyl-4-phenylbutyrate (HMPB, a 4-PB metabolite analog chemically synthesized in our laboratory) and 4-oxo-1,2,3,4-tetrahydro-naphthalene-carboxylate (OTNC, from the chemical library screening) significantly increased the proportion of canalicular Abcb11^R1128C protein. GPB, PA, ursodeoxycholic acid (UDCA), alone or in combination with 4-PB, suberoylanilide hydroxamic acid (SAHA), C18, VX-445, and/or VX-661, significantly corrected both the traffic and the activity of Abcb11^R1128C. Such correctors could represent new pharmacological insights for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the transporter’s traffic. Full article

In plants, SPL is a distinct family of transcription factors. Its protein structure possesses a highly conserved SBP domain comprising two zinc finger structures and nuclear localization regions, and microRNAs (miR156) control the transcriptional expression of the majority of SPL genes. SPLs are key TFs in regulating organ morphogenesis, phase transition/floral induction, and yield-related traits in agronomic and horticultural crops. These biomolecules have been functionally characterized for their role in augmenting plant responses to abiotic and biotic stresses. Present research gaps and viewpoints are addressed herein. Using these extensive data, researchers can more comprehensively understand how SPL genes modulate agronomic features in different ways. Full article

SQUAMOSA promoter-binding protein-like (SPL) transcription factors specific to plants are vital for regulating growth, development, secondary metabolite biosynthesis, and responses to both biotic and abiotic stresses. Despite their importance, no systematic investigations or identifications of the SPL gene family in Ginkgo biloba have been conducted. In this study, we identified 13 SPL genes within the Ginkgo biloba reference genome, spanning seven chromosomes, and categorized these genes into six groups based on their phylogenetic relationships with Arabidopsis thaliana SPL gene families. Our analysis of gene structure, conserved domains, motifs, and miR156 target predictions indicates that GbSPLs are highly conserved across evolutionary timelines. Furthermore, synteny analysis highlighted that dispersed duplication events have expanded the SPL gene family in Ginkgo biloba. Examination of the cis-regulatory elements revealed that many GbSPL genes possess motifs associated with light, hormones, and stress, implying their involvement in flavonoid biosynthesis and adaptation to environmental conditions. RNA-Seq and qRT-PCR expression profiles of GbSPL genes across various tissues and low- and high-flavonoid leaves and during both short-term and long-term water stress illustrated their roles in flavonoid biosynthesis and responses to water stress. Subcellular localization experiments showed that GbSPL2 and GbSPL11 proteins are situated within the nucleus. Our research offers the first systematic characterization of the SPL gene family in Ginkgo biloba, establishing a valuable foundation for understanding their evolutionary background and functional roles in flavonoid biosynthesis and water stress response. Full article

Melanin is an important component of the body color of honeybees, and its formation changes with the age of a capped brood of bees. However, up to now, the regulatory mechanism of melanin formation in honeybees remains unclear. To analyze the differential expression profile of microRNAs (miRNAs) in worker bees of Apis mellifera and to reveal the regulatory roles of differentially expressed miRNAs (DEmiRNAs) and mRNAs in the formation process of melanin during the capped brood stage, we used sRNA-seq technology and related software to analyze samples from four key developmental stages during the capped brood stage, when body color develops in Apis mellifera, namely, mature larvae (L0), pre-pupae (PP3), early pupae (P6) and mid-pupae (P9). A total of 1291 miRNAs were identified by bioinformatics. Three comparison groups were analyzed: L0 vs. PP3, PP3 vs. P6, and P6 vs. P9. A total of 171, 94, and 19 DEmiRNAs were identified in these groups, respectively, which regulate 1481, 690, and 182 differentially expressed target mRNAs (target DEmRNAs). The functional analysis of target DEmRNAs indicated that DEmiRNAs might regulate the formation of capped brood melanin in honeybees by activating expression changes in key genes in signaling pathways, such as the Wnt signaling pathway, melanogenesis, and the Toll and Imd signaling pathway, through activating miR-315-x, miR-8, ple, yellow family genes, wnt1, etc. Our research provides a theoretical basis for future analysis of the regulatory role of miRNAs in the formation of melanin in honeybees. Full article

Rapeseed (Brassica napus) is highly susceptible to waterlogging during the seedling stage; however, most of the studies on its gene expression under waterlogging stress have focused on transcriptional regulation, with little work conducted on post-transcriptional regulation to date. To elucidate this regulatory network, comparative transcriptome and miRNA analyses in the leaves and roots of rapeseed Zhongshuang11 (ZS11) were performed. Differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) were identified by comparing the normal planting condition (the control group, CKT) with waterlogging treatment (WLT). DEGs identified in leaves and roots were enriched in different metabolic pathways, indicating their distinct mechanisms in response to waterlogging stress. In total, 68 and 82 DEmiRNAs were identified in leaves and roots, respectively, predicted to target 543 and 2122 DEGs in each tissue. Among these, 12 and 9 transcription factors (TFs) were exclusively targeted by DEmiRNAs in leaves and roots, respectively. Notably, six upregulated TFs in leaves were associated with the ethylene response and were predicted targets of bna-miR172 family members, and four TFs in roots participated in the ethylene response pathway. Furthermore, bna-miR169, along with novel-miR-23108 and novel-miR-42624 family members, played crucial roles in waterlogging response of rapeseed. Combining with the determination results of ethylene and jasmonic acid content, a preliminary model of miRNA-mediated gene expression regulation in rapeseed response to waterlogging stress was developed. These findings advance our understanding of transcriptional regulation under waterlogging and lay a theoretical foundation for improving rapeseed waterlogging tolerance. Full article