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Sequence dynamics and plastome evolution: decoding the complete chloroplast genome of Oenothera drummondii and comparative analysis within Oenothera (Onagraceae) 序列动力学与质体进化:石斛属(onagracae)叶绿体全基因组解码及石斛属比较分析
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-13 DOI: 10.1007/s10142-025-01752-5
Chang An, Wenbo Xu, Yixin Yao, Min Li, Yanxiang Lin, S. V. G. N. Priyadasrhani, Aya Elderini, Yan Cheng, Site Luo, Yuan Qin, Ping Zheng

Oenothera species are increasingly valued for their medicinal and ornamental qualities and serve as important models in classical cytoplasmic genetics research. The genus Oenothera L., one of the largest in the Onagraceae family, includes 18 subsections and two deep phylogenetic lineages, Clade A and Clade B. Analyzing high-quality chloroplast genomes can provide crucial insights into species classification and genus-level evolution. In this study, we report the complete chloroplast genome of Oenothera drummondii Hook., the first species from subsection Raimannia, with a total length of 167,177 bp and a GC content of 39.3%. This genome contains 129 genes and displays a typical quadripartite structure. Combining this genome with data from 16 publicly available chloroplast genomes, we conducted a comprehensive comparative and evolutionary analysis. Our results indicate that Clade B species diverged independently from Clade A species. Within Clade A, species from subsection Muniza form a distinct branch, while O. drummondii clusters closely with species from subsection Oenothera. Phylogenetic analysis correlates well with chloroplast genome structural differences, such as the loss of the infA gene in Clade B species, the expansion of the IR regions in Muniza, and a shared large inversion in the LSC region among Raimannia and Oenothera species. We also identified repeat sequences, six highly variable genes, and positively selected genes among the 17 chloroplast genomes analyzed. These findings offer valuable insights into the evolutionary processes of Oenothera species and provide a foundation for the development of future molecular markers based on the identified genes and structural variations.

Graphical Abstract

酒花属植物因其药用和观赏价值日益受到重视,是经典细胞质遗传学研究的重要模型。Oenothera L.属是onagracae科中最大的属之一,包括18个亚科和两个较深的系统发育谱系,进化枝A和进化枝b。分析高质量的叶绿体基因组可以为物种分类和属水平进化提供重要的见解。在这项研究中,我们报道了drummondii Oenothera的完整叶绿体基因组。,为第一种,总长度为167,177 bp, GC含量为39.3%。该基因组包含129个基因,呈现典型的四部结构。将该基因组与16个公开可用的叶绿体基因组数据相结合,我们进行了全面的比较和进化分析。我们的研究结果表明,B支系物种独立于A支系物种。在A枝中,来自Muniza分支的物种形成一个独立的分支,而O. drummondii与来自Oenothera分支的物种紧密聚集。系统发育分析与叶绿体基因组结构差异密切相关,如进化枝B物种的infA基因缺失,Muniza物种的IR区域扩大,Raimannia和Oenothera物种的LSC区域都有较大的反转。我们还在分析的17个叶绿体基因组中鉴定了重复序列、6个高可变基因和正选择基因。这些研究结果为进一步了解蛇麻属物种的进化过程提供了有价值的见解,并为未来基于已鉴定基因和结构变异的分子标记的开发奠定了基础。图形抽象
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引用次数: 0
Transgenic gamete cleaning system enabled high-throughput screening for non-transgenic gene-edited plants 转基因配子清洗系统实现了非转基因基因编辑植物的高通量筛选
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-12 DOI: 10.1007/s10142-025-01782-z
Shifei Sang, Mengru Liu, Tian Tian, Shiqian Zhang

The breakthrough progress in gene editing technology has established a brand-new paradigm for gene function analysis and crop genetic improvement, and has already become the core driving force in modern agricultural biotechnology. However, traditional methods for screening edited individual plants without T-DNA insertion in their offspring are time-consuming and labor-intensive. To accelerate the identification of T-DNA-free edited plants, researchers have continuously explored various strategies to improve screening efficiency, achieving some success. Despite this progress, these strategies also exhibit varying degrees of limitations. Recently, research teams led by Cheng and Sun (2025) and Zhu et al. (2025) constructed gamete elimination systems, successfully achieving a 100% non-transgenic status in the mutant plants. This innovative approach has transformed traditional molecular testing from a "laboratory-dependent" model to "field-based real-time decision-making" providing an efficient and cost-effective solution for precision breeding.

基因编辑技术的突破性进展,为基因功能分析和作物遗传改良建立了全新的范式,已成为现代农业生物技术的核心驱动力。然而,筛选后代中没有T-DNA插入的编辑过的植物个体的传统方法既耗时又费力。为了加快对无t - dna编辑植物的鉴定,研究人员不断探索各种策略来提高筛选效率,并取得了一定的成功。尽管取得了这些进展,但这些策略也表现出不同程度的局限性。最近,Cheng和Sun(2025)以及Zhu等(2025)的研究团队构建了配子消除系统,成功地在突变植物中实现了100%非转基因状态。这种创新的方法将传统的分子检测从“依赖实验室”的模式转变为“基于现场的实时决策”,为精确育种提供了高效和经济的解决方案。
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引用次数: 0
Analyses of gene families, allelic variation and VIGS reveal that GheIF3M.2 is significantly associated with dwarfism and the absence of flower buds in upland cotton 基因家族分析、等位基因变异分析和VIGS分析表明,2与陆地棉花的侏儒症和缺少花蕾有显著关系。
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-11 DOI: 10.1007/s10142-025-01773-0
Dandan Li, Xueli Zhang, Junning Yang, Xuefeng Guo, Ying Li, Qiwen Yang, Wenmin Yuan, Tingting Zhang, Caixiang Wang, Jian Li, Junji Su

Eukaryotic translation initiation factor 3 (eIF3), the largest eukaryotic initiation factor, regulates mRNA translation initiation. While eIF3 has been extensively studied in various plant species, research on eIF3 in upland cotton remains limited. A total of 60 GheIF3s were identified using a bioinformatics approach, and comprehensive characteristic analysis was conducted in upland cotton. The results revealed that the different subunits of the GheIF3s were strongly conserved in both structural and evolutionary relationships. RNA-seq and qRT‒PCR results revealed that the expression levels of GheIF3L.1 and GheIF3M.2 in early‒maturing varieties were significantly greater than those in late-maturing varieties. Furthermore, no single-nucleotide polymorphisms (SNPs) were detected in GheIF3L.1, and a SNP (A05:105181831, T/G) significantly related to the flowering period within the coding sequence of GheIF3M.2 was identified. The flowering time of the varieties carrying the GG allele was significantly earlier than that of the varieties carrying the TT allele, which was verified in both early − flowering and late-flowering varieties via Sanger sequencing. Genetic diversity analysis revealed that the gene region differed between early − and late − maturing varieties. Virus-induced gene silencing (VIGS) results indicated that the silenced plants (TRV:GheIF3M.2) presented a significant decrease in plant height; inhibited flower bud differentiation; and significantly decreased IAA, GA3, and BR contents. These analyses elucidated the functions of GheIF3s in upland cotton and provided genetic resources related to plant morphology and early maturity.

真核生物翻译起始因子3 (Eukaryotic translation initiation factor 3, eIF3)是最大的真核生物起始因子,主要调控mRNA翻译起始。虽然eIF3在各种植物物种中得到了广泛的研究,但对陆地棉花中eIF3的研究仍然有限。利用生物信息学方法鉴定了60个ghif3s,并对其进行了综合性状分析。结果表明,不同亚基的GheIF3s在结构和进化关系上都是高度保守的。RNA-seq和qRT-PCR结果显示,1和GheIF3M。在早熟品种中2显著大于晚熟品种。此外,在GheIF3L中未检测到单核苷酸多态性。1,编码序列中有一个与花期显著相关的SNP (A05:105181831, T/G)。2已确定。携带GG等位基因的品种的开花时间明显早于携带TT等位基因的品种,这一点通过Sanger测序在早花期和晚花期品种中都得到了证实。遗传多样性分析表明早熟和晚熟品种的基因区域存在差异。病毒诱导基因沉默(VIGS)结果表明,沉默植株(TRV:GheIF3M.2)株高显著降低;抑制花芽分化;显著降低了IAA、GA3和BR含量。这些分析阐明了ghif3s在陆地棉中的功能,并为棉花植株形态和早熟提供了遗传资源。
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引用次数: 0
Genetic evaluation of CRISPR-Cas9 off-target effects from deleterious mutations on Drosophila male single X chromosome 果蝇雄性单X染色体有害突变对CRISPR-Cas9脱靶效应的遗传评价
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-10 DOI: 10.1007/s10142-025-01775-y
Wei Bian, David W. J. Mcquarrie, Irmgard U. Haussmann, Roland Arnold, Matthias Soller

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease protein 9 (Cas9) is a powerful tool used for genome engineering, but concerns remain about off-target effects. Here we evaluate potential deleterious effects of CRISPR-Cas9 by combining sequence analysis and the genetics of the male X chromosome in a Drosophila model. Since males have only one X chromosome deleterious mutations on the X chromosome will manifest in reducing viability or result in visible phenotypes and thus provide sensitive readouts of off-target activity. Our data do not support large scale off-target effects in Drosophila. To optimize sgRNA selection, we incorporated off-target evaluation into the PlatinumCRISPr sgRNA selection tool for a broad range of organisms.

聚集规律间隔短回文重复序列(CRISPR)相关核酸酶蛋白9 (Cas9)是用于基因组工程的强大工具,但对脱靶效应的担忧仍然存在。在这里,我们通过在果蝇模型中结合序列分析和雄性X染色体的遗传学来评估CRISPR-Cas9的潜在有害作用。由于男性只有一条X染色体,X染色体上的有害突变将表现为生存能力降低或导致可见表型,从而提供脱靶活性的敏感读数。我们的数据不支持果蝇的大规模脱靶效应。为了优化sgRNA选择,我们将脱靶评估纳入PlatinumCRISPr sgRNA选择工具,用于广泛的生物。
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引用次数: 0
CRISPR/Cas9-mediated generation of GATA3 knockout in Bovine Fibroblast and MDBK cell lines to assess sgRNAs targeting efficiency CRISPR/ cas9介导的牛成纤维细胞和MDBK细胞系中GATA3基因敲除的产生以评估sgRNAs靶向效率。
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-09 DOI: 10.1007/s10142-025-01774-z
Qurat Ul Ain, Afshan McCarthy, Asif Nadeem, Maryam Javed, Kathy Niakan, Ali Fouladi Nashta

GATA3 is expressed in the outer cells of the morula stage during embryonic development and is considered a key driver of the regulation of early lineage development in bovines. This research presents an optimised somatic cell validation resource, successfully generating GATA3 knockout (KO) Bovine Fetal Fibroblasts and MDBK cells using CRISPR/Cas9-mediated genome editing for their future implications in vivo studies designed to definitively understand the role of GATA3 in cell lineage specification and bovine embryo development. This involved designing single-guide RNAs (sgRNAs) targeting different regions of the GATA3 gene, cloning them into the px459 plasmid, delivering the CRISPR clone into bovine fibroblast cells and the MDBK cell line, screening for successful targeting and knockouts, and MiSeq analysis to verify successful disruption of the GATA3 gene. A total of eleven guides were designed targeting the functional domains in Exons 4 and 5 and the transcription initiation site in Exon 2. Designed guides were first optimized and screened using an in vitro cleavage assay. The guides with the best cutting efficiencies were then tested in vivo by targeting bovine fetal fibroblast (BFFs) and MDBK cell line followed by MiSeq analysis to verify the successful knockouts. A total of two effective guides were identified targeting the zinc-finger (ZnF) functional domains of the GATA3 gene (sgRNA#5 and sgRNA#8 in Exon 4 and Exon 5, respectively) and one in Exon 2 (sgRNA#1) targeting the transcription initiation site of the GATA3 gene. MiSeq data from targeted bovine cells showed indel frequency of 47.40%, 55.5%, and 42.4% in bovine fetal fibroblasts, 11.03%, 28.9% and 7.3% for MDBK cells for top three sgRNAs. Overall, MiSeq data for 3 selected sgRNAs showed successful disruption of the GATA3 gene, inserting a base pair 2–3 bp upstream of the PAM site, ultimately resulting in a premature stop codon TAA in the downstream region. This study established and validated highly efficient sgRNAs targeting the GATA3 gene, forming a molecular basis for forthcoming functional investigations in bovine embryos to explore gene function and protein-level effects.

GATA3在胚胎发育期间的桑葚胚阶段的外细胞中表达,被认为是牛早期谱系发育调控的关键驱动因素。本研究提出了一种优化的体细胞验证资源,利用CRISPR/ cas9介导的基因组编辑技术成功生成了GATA3敲除(KO)牛胎儿成纤维细胞和MDBK细胞,用于未来的体内研究,旨在明确了解GATA3在细胞系规范和牛胚胎发育中的作用。这包括设计针对GATA3基因不同区域的单导rna (sgRNAs),将其克隆到px459质粒中,将CRISPR克隆体传递到牛成纤维细胞和MDBK细胞系中,筛选成功的靶向和敲除,并进行MiSeq分析以验证GATA3基因的成功破坏。针对外显子4和5的功能域以及外显子2的转录起始位点,共设计了11个向导。设计的指南首先优化和筛选使用体外裂解试验。然后通过牛胎成纤维细胞(BFFs)和MDBK细胞系进行体内测试,并进行MiSeq分析以验证成功敲除。共鉴定出两个靶向GATA3基因锌指(ZnF)功能域(分别位于外显子4和外显子5中的sgRNA#5和sgRNA#8)和一个位于外显子2中的sgRNA#1,靶向GATA3基因的转录起始位点。靶牛细胞的MiSeq数据显示,牛胎儿成纤维细胞的indel频率分别为47.40%、55.5%和42.4%,MDBK细胞的indel频率分别为11.03%、28.9%和7.3%。总体而言,3个选定的sgRNAs的MiSeq数据显示GATA3基因成功中断,在PAM位点上游插入一个碱基对2-3 bp,最终导致下游区域过早停止密码子TAA。本研究建立并验证了靶向GATA3基因的高效sgRNAs,为今后在牛胚胎中进行功能研究以探索基因功能和蛋白水平效应奠定了分子基础。
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引用次数: 0
Paeonol improves preeclampsia by inhibiting ferroptosis by regulating ACSL4 protein ubiquitination 丹皮酚通过调节ACSL4蛋白泛素化抑制铁下垂改善子痫前期。
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-08 DOI: 10.1007/s10142-025-01783-y
Wenjuan Wu, Huanping Wang, Yu Wang, Haiying Wu

This study aimed to investigate the effects of paeonol (pae) on blood pressure, tissue damage, and the fetuses and placentas in a preeclampsia (PE) rat model induced by L-NAME, and to explore the potential regulatory mechanism involving the NEDD4L-ACSL4 axis. By quantitatively analyzing urinary protein, blood pressure, and sFlt-1 levels, the role of pae in the PE rat model was evaluated. The effects of pae on HTR-8/SVneo and primary trophoblast cells were investigated using a cell model. The role of pae in the process of NEDD4L-mediated ACSL4 ubiquitination was determined through experiments such as Co-IP and ubiquitination assays. Pae reduced blood pressure, urinary protein, and sFlt-1 levels in a PE rat model, increased the fetal survival rate, and improved placental and renal damage. Mechanistically, pae mediated the ubiquitination level of ACSL4 by promoting the interaction between ACSL4 and NEDD4L, thereby reversing hypoxia-induced ferroptosis. In brief, pae further inhibited ferroptosis by facilitating NEDD4L-mediated ACSL4 ubiquitination, exerting a significant improving effect on blood pressure and tissue damage in PE. Thus, it provided a new strategy for the treatment of PE and laid a foundation for further research on the mechanism of action of pae and its related compounds.

本研究旨在探讨丹皮酚(pae)对L-NAME诱导的子痫前期(PE)大鼠模型血压、组织损伤及胎儿和胎盘的影响,并探讨其与NEDD4L-ACSL4轴相关的潜在调控机制。通过定量分析尿蛋白、血压和sFlt-1水平,评估pae在PE大鼠模型中的作用。采用细胞模型研究了page对HTR-8/SVneo和原代滋养细胞的影响。通过Co-IP和泛素化分析等实验确定了page在nedd4l介导的ACSL4泛素化过程中的作用。在PE大鼠模型中,Pae降低了血压、尿蛋白和sFlt-1水平,增加了胎儿存活率,改善了胎盘和肾脏损伤。在机制上,page通过促进ACSL4与NEDD4L的相互作用,介导ACSL4的泛素化水平,从而逆转缺氧诱导的铁下垂。总之,pae通过促进nedd4l介导的ACSL4泛素化进一步抑制铁下垂,对PE患者血压和组织损伤有显著改善作用。从而为PE的治疗提供了新的策略,并为进一步研究pae及其相关化合物的作用机制奠定了基础。
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引用次数: 0
Exosomal miRNA-25-3p from platelet-rich plasma alleviates chondrocyte pyroptosis and knee osteoarthritis by regulating MAP4K2/Hippo/TNFAIP3 pathway 富血小板血浆外泌体miRNA-25-3p通过调节MAP4K2/Hippo/TNFAIP3通路减轻软骨细胞焦亡和膝关节骨关节炎。
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-08 DOI: 10.1007/s10142-025-01780-1
Jing Wang, Jingzhi Li, Xiuming He, Hongtao Zhang, Xiaoyu Zheng, Han Luo, Zhenyu Yang, Xiaozhong Zhou

Recent studies have highlighted the efficacy of platelet-rich plasma-derived exosomes (PRP-Exo) in managing osteoarthritis (OA). This research aimed at exploring the effect and mechanism of PRP-Exo-mediated intervention in chondrocyte pyroptosis and knee osteoarthritis. In this study, PRP was collected from human volunteers and rats, and the PRP-Exo was extracted, which was employed in the in vitro and in vivo OA model. The molecular interaction was analyzed by luciferase reporter assay, Chromatin immunoprecipitation and Electrophoretic Mobility Shift Assay experiment. Cell pyroptosis was analyzed by flow cytometry and biomarkers detection. Degrees of cartilage injury were detected using Alcian Blue, Safranin O Fast Green, and Toluidine Blue O staining. Our results showed that PRP-Exo had a similar effect with PRP on alleviating chondrocyte pyroptosis and OA progression. PRP-Exo functioned by transferring miR-25-3p to chondrocyte, which targeting to MAP4K2 and regulating Hippo pathway. MiR-25-3p inhibition weaken the effect of PRP-Exo, while MAP4K2 overexpression reversed the effect of miR-25-3p overexpression. Besides, TNFAIP3 was confirmed as a downstream molecular of MAP4K2/Hippo pathway. The effect of miR-25-3p was also confirmed in a rat OA model. Collectively, this study elucidated that PRP-Exo derived miR-25-3p alleviated chondrocyte pyroptosis and OA progression by regulating the MAP4K2/Hippo/TNFAIP3 pathway.

最近的研究强调了富血小板血浆源性外泌体(PRP-Exo)在治疗骨关节炎(OA)中的功效。本研究旨在探讨prp - exo介导的干预在软骨细胞焦亡和膝关节骨关节炎中的作用和机制。本研究收集人类志愿者和大鼠的PRP,提取PRP- exo,用于体外和体内OA模型。采用荧光素酶报告基因法、染色质免疫沉淀法和电泳迁移位移法分析分子间相互作用。采用流式细胞术和生物标志物检测分析细胞焦亡情况。采用阿利新蓝、红红素O快绿、甲苯胺蓝O染色检测软骨损伤程度。我们的研究结果表明,PRP- exo与PRP在缓解软骨细胞焦亡和OA进展方面具有相似的作用。PRP-Exo通过将miR-25-3p转移到软骨细胞,靶向MAP4K2并调节Hippo通路发挥作用。MiR-25-3p抑制削弱了PRP-Exo的作用,而MAP4K2过表达逆转了MiR-25-3p过表达的作用。此外,TNFAIP3被证实是MAP4K2/Hippo通路的下游分子。在大鼠OA模型中也证实了miR-25-3p的作用。总的来说,本研究阐明了PRP-Exo衍生的miR-25-3p通过调节MAP4K2/Hippo/TNFAIP3通路减轻软骨细胞焦亡和OA进展。
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引用次数: 0
TROAP aggravates chemoresistance of colorectal cancer cells via lipogenesis by PI3K/Akt pathway and histone acetylation TROAP通过PI3K/Akt通路和组蛋白乙酰化,通过脂肪生成加重结直肠癌细胞的化疗耐药
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-06 DOI: 10.1007/s10142-025-01787-8
Ling-Ling Wang, Rui Zhang, Ning Li, Zheng-Guo Cui, Hua-Chuan Zheng

Trophinin-associated protein (TROAP) is a proline-rich cytoplasmic protein exclusively on the apical side of syncytiotrophoblasts and is associated with the microtubular cytoskeleton. We analyzed the expression, promoter methylation, and relevant pathways of TROAP in colorectal cancers (CRCs) using bioinformatics, validated TROAP expression with RT-PCR, western blot and immunohistochemistry, and examined its clinical implications. Its biological processes and molecular mechanisms were investigated by tumor xenograft models, TUNEL, CCK-8, flow cytometry, wound healing and transwell assays, Nile red staining, western blot, proteomic and bioinformatics analysis. TROAP expression was significantly elevated in CRC compared to that in normal mucosa (p < 0.05). TROAP mRNA expression was positively correlated with p53 mutation, poor clinical outcome and favorable prognosis in CRC (p < 0.05). TROAP methylation was inversely correlated with its mRNA expression, lower clinicopathological staging, and non-mutant p53 expression (p < 0.05). TROAP expression was positively associated with younger age, distal metastasis, TNM stage, differentiation, and poor prognosis in CRC patients (p < 0.05). TROAP expression was closely linked to cell cycle, nuclear division, chromatid segregation, calcium and Wnt signaling pathway, ECM regulators and glycoproteins, cell senescence, CPCR-ligand, iron ion and heparin binding in CRCs (p < 0.05). TROAP promoted cell proliferation, resistance to apoptosis and pyroptosis, as well as cell migration, invasion, and epithelial-mesenchymal transition in CRC cells. TROAP aggravated lipid droplet formation and subsequent chemoresistance via de novo lipogenesis via histone acetylation and PI3K/Akt pathway. Aberrant TROAP expression could serve as a biomarker for aggressive behavior and poor prognosis in CRCs, as well as a molecular target for gene therapy.

营养蛋白相关蛋白(TROAP)是一种富含脯氨酸的细胞质蛋白,仅存在于合胞滋养细胞的顶端,与微管细胞骨架有关。我们利用生物信息学分析了TROAP在结直肠癌(crc)中的表达、启动子甲基化和相关途径,并利用RT-PCR、western blot和免疫组织化学验证了TROAP的表达,并研究了其临床意义。通过肿瘤异种移植模型、TUNEL、CCK-8、流式细胞术、伤口愈合和transwell实验、尼罗红染色、western blot、蛋白质组学和生物信息学分析研究其生物学过程和分子机制。与正常黏膜相比,结直肠癌中TROAP表达显著升高(p < 0.05)。TROAP mRNA表达与CRC中p53突变、临床预后不良、预后良好呈正相关(p < 0.05)。TROAP甲基化与其mRNA表达、较低的临床病理分期和非突变型p53表达呈负相关(p < 0.05)。TROAP表达与结直肠癌患者的年龄、远端转移、TNM分期、分化、预后不良呈正相关(p < 0.05)。TROAP的表达与细胞周期、核分裂、染色单体分离、钙和Wnt信号通路、ECM调节因子和糖蛋白、细胞衰老、cpcr -配体、铁离子和肝素在crc中的结合密切相关(p < 0.05)。TROAP促进结直肠癌细胞的增殖、抗凋亡和焦亡,以及细胞迁移、侵袭和上皮间质转化。TROAP通过组蛋白乙酰化和PI3K/Akt途径,通过重新生成脂肪,加重脂滴形成和随后的化疗耐药。异常的TROAP表达可以作为恶性肿瘤侵袭性行为和预后不良的生物标志物,以及基因治疗的分子靶点。
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引用次数: 0
Transcriptome analysis reveals reduced lipid accumulation and mitochondrial metabolic remodeling in ADCY3-overexpressing adipocytes 转录组分析显示,adcy3过表达脂肪细胞的脂质积累和线粒体代谢重塑减少
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-06 DOI: 10.1007/s10142-025-01789-6
Lu Liu, Houxue Cui, Zhongfang Xiang, Nanxi Dong, Dong Niu

Excessive adipose tissue accumulation adversely impacts the health of both humans and livestock. Adenylyl cyclase 3 (ADCY3) is a promising anti-obesity target, yet its regulatory role in adipogenesis remains incompletely understood. Our findings revealed a dynamic pattern of ADCY3 expression during adipogenesis and lipid droplet (LDs) accumulation. Functional analyses demonstrated that ADCY3 overexpression impaired adipogenesis by downregulating adipogenic transcription factors CEBPα and PPARγ. Furthermore, it reduced both the number and size of LDs through suppressing triglyceride synthesis and fatty acid metabolism, concomitantly downregulating key genes involved in LDs formation (PLIN1, CIDEC, FIT2, and Seipin), as well as factors mediating glycerol ester synthesis and fatty acid metabolism (DGAT1, DGAT2, ACC, SCD, FASN, and ACSL1). Transcriptomic profiling revealed that ADCY3 overexpression suppressed PPARγ signaling, leading to the downregulation of oxidative phosphorylation genes encoded by both the nuclear and mitochondrial genomes. Our results implicate ADCY3 in the regulation of lipid metabolism, with the speculative involvement of mitochondrial metabolic remodeling. This perspective offers a framework for developing future interventions against excessive lipid deposition.

过多的脂肪组织积累对人类和牲畜的健康都有不利影响。腺苷酸环化酶3 (ADCY3)是一种很有前景的抗肥胖靶点,但其在脂肪形成中的调节作用仍不完全清楚。我们的研究结果揭示了ADCY3在脂肪形成和脂滴(ld)积累过程中的动态表达模式。功能分析表明,ADCY3过表达通过下调脂肪生成转录因子CEBPα和PPARγ来抑制脂肪生成。此外,它通过抑制甘油三酯合成和脂肪酸代谢来减少ld的数量和大小,同时下调参与ld形成的关键基因(PLIN1、CIDEC、FIT2和Seipin),以及介导甘油酯合成和脂肪酸代谢的因子(DGAT1、DGAT2、ACC、SCD、FASN和ACSL1)。转录组学分析显示,ADCY3过表达抑制PPARγ信号,导致核和线粒体基因组编码的氧化磷酸化基因下调。我们的研究结果暗示ADCY3参与脂质代谢的调节,推测参与了线粒体代谢重塑。这一观点为未来针对过度脂质沉积的干预提供了一个框架。
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引用次数: 0
DGEAR: a web-based application for differential gene expression analysis and downstream functional insights DGEAR:一个基于网络的应用程序,用于差异基因表达分析和下游功能见解
IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2025-12-05 DOI: 10.1007/s10142-025-01764-1
Koushik Bardhan, Chiranjib Sarkar

The rapid expansion of transcriptomic data has necessitated the development of efficient and scalable analytical frameworks for Differential Gene Expression (DGE) Analysis. We present a web-based tool implementing the DGEAR (Differential Gene Expression Analysis with R), designed using a three-tier architecture to enhance usability, performance, and modularity. The system comprises a frontend user interface (UI) for seamless data submission and visualization, a middleware processing layer handling computational tasks with an Application Programming Interface, and a backend data layer for secure data management and efficient execution of statistical analyses. The DGEAR algorithm integrates multiple statistical methods and an ensemble model with a cut-off-based majority voting strategy, ensuring robustness, flexibility, and accuracy in identifying differentially expressed genes from microarray and RNA-seq datasets. Furthermore, DGEAR integrates gene set enrichment analysis and PPI network construction, giving a major head start in downstream analysis. The web tool supports custom parameter selection, data visualization, and end-to-end encryption, making it securely accessible to researchers and clinicians. Generated output data can be directly accessible and can be downloaded by the user. This platform significantly streamlines transcriptomic analysis, providing an intuitive, high-performance environment for bioinformatics investigations, and is publicly available at https://dgear.compbiosysnbu.in/.

转录组学数据的快速扩展要求开发高效和可扩展的差异基因表达(DGE)分析框架。我们提出了一个基于web的工具实现DGEAR(差异基因表达分析与R),设计使用三层架构,以提高可用性,性能和模块化。该系统包括一个用于无缝数据提交和可视化的前端用户界面(UI),一个通过应用程序编程接口处理计算任务的中间件处理层,以及一个用于安全数据管理和有效执行统计分析的后端数据层。DGEAR算法集成了多种统计方法和基于截断的多数投票策略的集成模型,确保了从微阵列和RNA-seq数据集识别差异表达基因的鲁棒性、灵活性和准确性。此外,DGEAR集成了基因集富集分析和PPI网络构建,为下游分析提供了重要的先机。该网络工具支持自定义参数选择、数据可视化和端到端加密,使研究人员和临床医生可以安全地访问它。生成的输出数据可以被用户直接访问和下载。该平台显著简化了转录组学分析,为生物信息学研究提供了直观、高性能的环境,并可在https://dgear.compbiosysnbu.in/上公开获取。
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引用次数: 0
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Functional & Integrative Genomics
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