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PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗

PubMed2017

Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma.

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC.

Carcinoma, Squamous Cell↗

PubMed2023

MYH16 upregulation is associated with lung adenocarcinoma aggressiveness and immune infiltration.

Myosin heavy chain 16 (MYH16) may significantly affect cell cycle progression. Nevertheless, there is a lack of evidence about the clinical relevance of MYH16 upregulation in pan cancers, including lung adenocarcinoma (LUAD). MYH16 expression patterns were evaluated in various bioinformatics databases using The Cancer Genome Atlas data set. Clinical and pathological factor data were employed to risk-stratify patients. The Kaplan-Meier plotter approach was used to estimate survival rates. Tumor immune infiltration was explored via the TIMER tool, and gene set enrichment analysis (GSEA) was used to identify the pathways involved in MYH16 upregulation. The results showed that MYH16 was abnormally upregulated in pan cancers, including LUAD. MYH16 expression induction in LUAD was found to be related to the tumor stage. Furthermore, MYH16 upregulation was correlated with LUAD development and worse overall survival, particularly in women. Notably, MYH16 overexpression in LUAD tissues corresponded to the amount of immune infiltration in the tumor. Additionally, univariate Cox hazard regression analysis revealed that MYH16 may be an independent prognostic indicator for LUAD. Furthermore, a nomogram was constructed according to MYH16 expression and clinical characteristics. BMP6 expression deficiency may be a key factor contributing to MYH16 upregulation in LUAD. Finally, GSEA demonstrated that MYH16 might mediate meiosis and gene silencing through RNA signaling pathways. This study, for the first time, showed that MYH16 upregulation in LUAD is associated with various risk factors, increased cancer aggressiveness, enhanced infiltration of tumor immune cells, and reduced survival rates.

Female↗

PubMed2026

NFS1 activates PI3K/AKT/mTOR signaling to upregulate GPX4 expression and enhance ferroptosis resistance in osteosarcoma.

Osteosarcoma continues to exhibit poor survival outcomes due to chemoresistance and metastasis, with metabolic reprogramming and ferroptosis resistance being key features of tumor heterogeneity, yet their upstream regulators remain poorly defined. NFS1, a cysteine desulfurase essential for iron-sulfur cluster biogenesis, protects multiple cancers from ferroptosis, but its role in osteosarcoma is unknown. In this study, we performed a transcriptomic meta-analysis and found that NFS1 expression was significantly upregulated in osteosarcoma tissues, with further elevation in metastatic lesions, and high NFS1 expression correlated with poor overall survival. Genome‑wide CRISPR screening data revealed a marked NFS1 dependency in osteosarcoma cell lines. Functionally, NFS1 promoted cell proliferation, migration, and invasion, whereas its knockdown suppressed these phenotypes. Using single‑cell RNA sequencing data from 27 osteosarcoma specimens, we applied a multi‑algorithm glycolytic scoring framework and observed NFS1 enrichment in highly glycolytic malignant cells, along with an association with PI3K/AKT/mTOR pathway activation. Mechanistically, NFS1 selectively enhanced PI3K, AKT, and mTOR phosphorylation without altering total protein levels, and upregulated GPX4, a central ferroptosis suppressor, leading to elevated ferroptosis resistance scores in NFS1‑high malignant cells. Collectively, these findings identify a previously unrecognized NFS1-PI3K/AKT/mTOR-GPX4 regulatory axis in osteosarcoma, linking metabolic reprogramming to ferroptosis resistance, and suggest that NFS1 functions as an oncogenic driver, as well as a promising prognostic biomarker and therapeutic target in osteosarcoma.

Humans↗

PubMed2025

Exosomal proteomics reveals fatty acid metabolism linked to gefitinib resistance in non-small cell lung cancer.

Exosomes play a crucial role in the transmission of drug resistance in tumors. However, the mechanism of exosomes-mediated transmission in non-small cell lung cancer (NSCLC) under gefitinib treatment remains limited. In this work, we demonstrated that exosomes derived from HCC827/GR cells (drug-resistant) enhanced the survivability of HCC827 cells (drug-sensitive) under treatment with gefitinib. A total of 157 shared upregulated proteins between exosomes and their parent cells were identified in the comparison of the gefitinib-resistant groups versus the gefitinib-sensitive groups. Notably, 69 of these shared proteins are enzymes, and many of them were enriched in pathways related to fatty acid metabolism. Among these enzymes involved in fatty acid metabolism, ACC1 exhibited the highest fold change in upregulated expression in both drug-resistant groups (exosomes and cells). Moreover, the expression of ACC1 was upregulated in gefitinib-sensitive cells after uptake of exosomes from gefitinib-resistant cells. The role of ACC1 in enhancing the survival of HCC827/GR cells under gefitinib treatment was demonstrated using an inhibitor and siRNA-mediated knockdown. Specifically, the upregulated ACC1 stabilized fatty acid oxidation and reactive oxygen species levels in HCC827/GR cells, thereby maintaining cellular metabolic homeostasis. Collectively, this work reveals the transmission of drug resistance in NSCLC via exosomes that carry the ACC1 protein.

Humans↗

PubMed2026

Transcription Factor SP1 Drives Myocardial Ischemia/reperfusion Injury By Transcription Activation-mediated GADD45G Upregulation.

Myocardial ischemia-reperfusion injury (MIRI) is an unresolved clinically fatal complication in the management of acute myocardial infarction (AMI). Growth arrest and DNA damage-inducible gene 45 Gamma (GADD45G) plays a vital role in the regulation of MIRI. However, the underlying mechanisms remain unclear. GADD45G and SP1 expression were upregulated in hypoxia/reoxygenation (H/R)-treated H9C2 cells. H/R treatment repressed H9C2 cell viability, and induced apoptosis, oxidative stress, and inflammatory response. Moreover, GADD45G deficiency could relieve H/R-triggered H9C2 cell injury. In mechanism, SP1 was a transcription factor of GADD45G and activated the transcription of GADD45G via binding to its promoter region. Besides, SP1 knockdown alleviated MI/R-induced pathological damage in the myocardial tissue of rats by regulating GADD45G. In conclusion, SP1 could promote H/R-induced cardiomyocyte injury and MI/R-caused rat myocardial tissue pathological injury by increasing GADD45G, providing a promising therapeutic target for MIRI treatment.

Animals↗

PubMed2014

Upregulation of TLR2 expression is induced by estrogen via an estrogen-response element (ERE).

TLR2 and estrogen are both thought to be involved in the pathogenesis of RA; however, it is unknown if there is an association between estrogen and TLR2. In this report, we treated PMA-differentiated THP-1 cells with 17β-estradiol (E2) and observed increases in TLR2 mRNA and protein levels by real-time quantitative PCR and western blot. Transfection of THP-1 cells with a series of 5'-deleted TLR2 promoter-luciferase constructs revealed that E2 enhanced TLR2 transcriptional activity in an estrogen receptor alpha (ERα)-dependent pattern. An estrogen receptor response element (ERE) was identified 251 bases upstream of the TLR2 promoter, and electrophoretic mobility shift assay and chromatin immunoprecipitations showed ERα binding was increased by E2. In summary, this work demonstrated that TLR2 is a new estrogen-regulated gene whose expression is upregulated through the interaction of ERα with an ERE in the promoter region.

Cell Line↗

PubMed2026

Nucleolin promotes neuropathic pain by increasing chromatin accessibility at the Ccl2 promoter in primary sensory neurons.

Nerve injury-induced transcriptional alterations in primary sensory neurons of the dorsal root ganglion (DRG) constitute a key molecular basis for the development of neuropathic pain. Nucleolin (NCL), a highly conserved multifunctional nucleolar protein, regulates gene transcription. Here, we identify that NCL is expressed exclusively in the nuclei of DRG neurons. Peripheral nerve injury time-dependently upregulates Ncl mRNA and NCL protein levels in injured DRG neurons. Blocking this upregulation through DRG microinjection of the adeno-associated virus 9 (AAV9) expressing an shRNA targeting Ncl attenuates nerve injury-induced increases of C-C motif chemokine ligand 2 (CCL2) mRNA and its protein in injured DRG and alleviates the development and maintenance of mechanical, heat and cold hypersensitivities. Conversely, mimicking DRG NCL upregulation through DRG microinjection of AAV9 carrying the full-length Ncl coding sequence increases Ccl2 mRNA and CCL2 protein levels in microinjected DRGs and produces neuropathic pain-like symptoms in the absence of nerve injury. Mechanistically, peripheral nerve injury increases NCL occupancy at the Ccl2 promoter and enhances chromatin accessibility at this locus, resulting in elevated CCL2 expression in injured DRG neurons, which is reversed by NCL knockdown. Given that Ncl mRNA is co-expressed with Ccl2 mRNA in individual DRG neurons, our findings suggest that NCL upregulation in the DRG contributes to neuropathic pain likely by increasing chromatin accessibility at the Ccl2 promoter in primary sensory neurons.

Animals↗

PubMed2026

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans↗

PubMed2024

Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders.

PURPOSE: Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation. METHODS: We reported an extended cohort of 44 affected individuals, of whom 19 are from the literature and 25 were previously unreported. RESULTS: Our analysis led to splitting the cohort into 2 entities. CONCLUSION: One group had variants in the cholesterol-binding motif of the transmembrane domain, with most of these being the recurrent variant c.1301A>G p.(Tyr434Cys). These variants probably lead to upregulation of tropomyosin receptor kinase B activity and to a severe phenotype of developmental delay/intellectual disability, muscular hypotonia, therapy-refractory epilepsy, visual impairment and blindness, and feeding difficulties. The second group had truncating variants or variants that presumably disturb the 3D structure of the protein leading to loss of function. These individuals had a remarkably milder phenotype of developmental delay, obesity, and hyperphagia.

Humans↗

PubMed2016

miR-503-3p promotes epithelial-mesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin.

Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelial-mesenchymal transition (EMT)-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 3' untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer.

Base Sequence↗

PubMed2026

Low-Grade Myofibroblastic Sarcoma Represents an Epigenetically Distinct Myofibroblastic Tumor With USP6 Upregulation and Stable Genome.

Low-grade myofibroblastic sarcoma (LGMS) is a rare, indolent mesenchymal neoplasm exhibiting myofibroblastic differentiation, with a propensity for local recurrence. The molecular basis of LGMS and its precise relationship with other histological mimics have remained largely undefined. To address this gap, we conducted the first comprehensive multiomics analysis of 6 LGMS cases, integrating whole-exome sequencing, RNA sequencing, and Illumina Methylation EPICv2 array profiling with comparative analysis against public sarcoma methylation cohorts and related fibroblastic tumors. Clinically, patients (median age 35.5 years) presented with small tumors (median size 1.45 cm), predominantly located in the head and neck, displaying classic histological features of diffusely infiltrative spindle cell fascicles with patchy mononuclear inflammation. Two of the 5 patients with follow-up developed local recurrence, and none metastasized (median follow-up duration 92.5 months). Genomically, all LGMS exhibited a low tumor mutational burden (median 2.31 mut/Mb) and a minimal fraction of genome altered, with TP53 and TSC2 deletions and NTRK1 and ERBB3 amplifications found in a subset of cases. No pathogenic fusions were detected. Transcriptomic profiling revealed a distinct signature featuring prominent USP6 overexpression and upregulation of inflammatory and immune-related genes, including CD274 (PD-L1), and enrichment of inflammatory and interferon-gamma response signatures. Epigenetically, LGMS formed a unique methylation cluster closest to inflammatory myofibroblastic tumor, with numerous differentially methylated regions and higher immune infiltration, particularly monocytes, compared with other fibroblastic tumors. These findings establish LGMS as a genomically stable, epigenetically distinct myofibroblastic sarcoma driven by USP6 overexpression and an inflammation-enriched transcriptome. They support its recognition as a standalone entity, facilitate integration into methylation-based sarcoma classifiers for improved diagnostic precision, and nominate USP6-associated pathways and immune checkpoint blockade as promising therapeutic strategies for recurrent or unresectable disease.

Humans↗

PubMed2026

Upregulation of Endogenous Serine Proteinases by SVMPs Contributes to Muscle Damage Induced by Bothrops atrox Venom.

In Brazil, approximately 25,000 snakebites occur annually, with Bothrops atrox responsible for most cases. Local morbidity is high, driven primarily by snake venom metalloproteases (SVMPs). The major SVMPs in B. atrox venom, Atroxlysin-Ia (ATXL) and Batroxrhagin (BATX), efficiently hydrolyze extracellular matrix proteins, inducing rapid hemorrhage and dermonecrosis. Thus, we characterized the composition of the exudate produced after SVMPs injection into the mice gastrocnemius muscle using proteomics. Muscle damage was evaluated by histological analysis. The composition of the exudate was analyzed by mass spectrometry. The SVMPs induced disorganization of muscle fibers and inflammatory cell migration. However, ATXL-induced a significantly higher neutrophil influx compared to BATX, likely triggered by an increase in CXCL16, suggesting a superior inflammatory capacity. In summary, despite being metalloproteases, these toxins exhibit distinct pathological profiles: ATXL is predominantly inflammatory, while BATX is more hemorrhagic. Interestingly, while endogenous serine proteinase levels were similar in both exudates, BATX showed significantly higher levels of proteinase inhibitors. Furthermore, identification of peptide bond cleavage sites revealed a pattern consistent with trypsin-like serine proteinases. These findings suggest that SVMPs not only damage tissue directly but also associate with the activation of host endogenous proteinases, which may contribute to the complex pathology of B. atrox envenomation, although direct causation remains to be established.

Animals↗

PubMed2014

Jarid2 is induced by TCR signalling and controls iNKT cell maturation.

Jarid2 is a reported component of three lysine methyltransferase complexes, polycomb repressive complex 2 (PRC2) that methylates histone 3 lysine 27 (H3K27), and GLP-G9a and SETDB1 complexes that methylate H3K9. Here we show that Jarid2 is upregulated upon TCR stimulation and during positive selection in the thymus. Mice lacking Jarid2 in T cells display an increase in the frequency of IL-4-producing promyelocytic leukemia zinc finger (PLZF)(hi) immature invariant natural killer T (iNKT) cells and innate-like CD8(+) cells; Itk-deficient mice, which have a similar increase of innate-like CD8(+) cells, show blunted upregulation of Jarid2 during positive selection. Jarid2 binds to the Zbtb16 locus, which encodes PLZF, and thymocytes lacking Jarid2 show increased PLZF and decreased H3K9me3 levels. Jarid2-deficient iNKT cells perturb Th17 differentiation, leading to reduced Th17-driven autoimmune pathology. Our results establish Jarid2 as a novel player in iNKT cell maturation that regulates PLZF expression by modulating H3K9 methylation.

Animals↗

PubMed2026

PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) remains an incurable haematological malignancy, underscoring the need for novel prognostic biomarkers and therapeutic targets. This study aimed to investigate the clinical and biological significance of peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PPRC1) in MM. METHODS: Expression and clinical data were obtained from public databases and an independent local cohort. Kaplan-Meier and Cox regression analyses were performed to evaluate prognostic value. Differential expression analysis, pathway enrichment analysis and single-cell RNA-seq data analysis were used to explore biological functions. PPRC1 was silenced in MM cell lines using siRNA to assess its effects on cell survival and oxidative phosphorylation. RESULTS: PPRC1 was significantly upregulated in MM and was associated with advanced disease stage and poor overall survival. Multivariate Cox analysis identified PPRC1 as an independent prognostic factor. A nomogram incorporating PPRC1 and revised-ISS improved survival prediction. Functional analyses revealed that PPRC1 was positively correlated with oxidative phosphorylation and oncogenic signalling pathways. A potential connection between PPRC1 expression and immune cell infiltration was observed. PPRC1 knockdown inhibited cell proliferation, induced cell cycle arrest and apoptosis and impaired oxidative phosphorylation in MM. CONCLUSIONS: PPRC1 acts as a prognostic biomarker and metabolic regulator in MM by sustaining mitochondrial oxidative phosphorylation. These findings highlight PPRC1 as a potential therapeutic target in MM.

Humans↗

PubMed2026

TMEM176B is co-expressed with TMEM176A and upregulated in peripheral blood monocytes of patients with primary Sjögren's syndrome.

OBJECTIVES: This study aims to determine the role of acid‑sensitive nonspecific cation channels transmembrane protein 176A (TMEM176A) and TMEM176B in autoimmune diseases, with a focus on primary Sjögren's Syndrome (pSS). METHODS: We examined the expression patterns of TMEM176A and TMEM176B across tissues and cells utilizing bulk RNA-seq and scRNA-seq datasets. Immunophenotyping analysis was performed by flow cytometry to compare CD62L expression between TMEM176B⁺ and TMEM176B⁻ monocytes. The proportion of TMEM176B+ cells in monocytes was interrogated in both pSS patients and healthy controls. Clinical correlations of TMEM176B with anti‑SSB antibody and complement C4 levels were also evaluated. RESULTS: TMEM176A and TMEM176B showed conserved co‑expression and were significantly upregulated in autoimmune diseases. TMEM176B⁺ monocytes displayed higher CD62L positivity rate than TMEM176B- monocytes. In pSS patients, the proportion of TMEM176B⁺ monocytes was elevated in total monocytes, classical monocytes (cMo) and intermediate monocytes (iMo). The proportion of TMEM176B+ monocytes positively correlated with anti‑SSB levels, while several TMEM176B-associated monocyte subset markers inversely correlated with C4. CONCLUSION: TMEM176A and TMEM176B are highly correlated. TMEM176B expression in monocytes is linked to pSS and may serve as a novel auxiliary diagnostic biomarker.

Humans↗

PubMed2025

Rice ETHYLENE RESPONSE FACTOR 101 increases leaf angle by upregulating BRASSINOSTEROID UPREGULATED 1.

The leaf angle (LA) is a critical component of plant architecture that directly influences photosynthetic efficiency and grain yield. In the present study, we found that ETHYLENE RESPONSE FACTOR 101 (OsERF101), an APETALA2/ethylene response factor, plays a role in LA formation. A null mutation in OsERF101 resulted in reduced LA, whereas transgenic plants overexpressing OsERF101 (OsERF101-OEs) exhibited increased LA. OsERF101 increased the development of the adaxial lamina joint (LJ). Transactivation assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis indicated that OsERF101 activated BRASSINOSTEROID UPREGULATED 1 (OsBU1) transcription by directly binding to its promoter. However, OsERF101 expression was suppressed by exogenous brassinosteroid (BR) treatment and elevated endogenous brassinolide (BL) levels during LJ development. Additionally, OsERF101 downregulated the expression of BR biosynthesis genes, including Brassinosteroid-deficient dwarf2 (OsBRD2) and CYP90B2/OsDWARF4, leading to reduced levels of endogenous BL, the most active BR, in OsERF101-OEs. These findings suggested that OsERF101 mediates a negative feedback loop that balances endogenous BR levels and signaling. Collectively, rice plants have evolved diverse regulatory mechanisms involving OsERF101 to tune LA formation and optimize plant architecture finely.

Oryza↗

PubMed2026

Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer-associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy-number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type-dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia-inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type-dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia-associated drug resistance in HCC.

Humans↗