Gene Reports最新文献_第4页

Epigenetic regulation in metabolic diseases and neuronal regeneration: Mechanisms, interactions, and therapeutic perspectives 代谢疾病和神经元再生中的表观遗传调控：机制、相互作用和治疗观点

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-04 DOI: 10.1016/j.genrep.2025.102400

Koyel Kar , Priyanka Chakraborty , Sailee Chowdhury , Kamal Singh , Mahendra Pratap Singh , Sandeep Kumar Singh

Neuronal damage in mammals often results in irreversible loss of function due to the limited regenerative capacity of the central nervous system. In contrast, lower vertebrates possess an intrinsic ability to regenerate neural tissue, providing valuable insight into potential repair mechanisms. Recent advances have revealed that epigenetic mechanisms—heritable yet reversible modifications that regulate gene expression without altering the DNA sequence—play a central role in orchestrating neuronal repair and regeneration.

This review focuses on the epigenetic regulation of neuronal regeneration, emphasizing how processes such as DNA methylation, histone modifications, and chromatin remodeling influence gene activation, glial responses, and stem cell reprogramming following neural injury. We discuss three major neural systems of therapeutic relevance—the spinal cord, inner ear, and neural retina—highlighting tissue-specific differences in regenerative potential and their underlying epigenetic signatures.

Furthermore, the review explores how epigenetic interventions, including inhibitors of histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), can reactivate dormant regenerative pathways. Understanding these dynamic and reversible molecular processes may enable the design of targeted therapies that enhance plasticity and promote functional recovery in non-regenerative tissues.

By integrating current knowledge and identifying key knowledge gaps, this work underscores the transformative potential of epigenetic modulation as a therapeutic strategy to overcome the regenerative limitations of the mammalian nervous system.

由于中枢神经系统的再生能力有限，哺乳动物的神经元损伤往往导致不可逆转的功能丧失。相比之下，低等脊椎动物具有再生神经组织的内在能力，这为潜在的修复机制提供了有价值的见解。最近的研究进展表明，表观遗传机制在调控神经元修复和再生过程中发挥着核心作用。表观遗传机制是指在不改变DNA序列的情况下调控基因表达的可遗传但可逆的修饰。这篇综述着重于神经元再生的表观遗传调控，强调DNA甲基化、组蛋白修饰和染色质重塑等过程如何影响神经损伤后的基因激活、神经胶质反应和干细胞重编程。我们讨论了与治疗相关的三个主要神经系统——脊髓、内耳和神经视网膜——强调了再生潜能的组织特异性差异及其潜在的表观遗传特征。此外，综述探讨了表观遗传干预，包括组蛋白去乙酰化酶（hdac）和DNA甲基转移酶（dnmt）抑制剂，如何重新激活休眠的再生途径。了解这些动态和可逆的分子过程可能有助于设计靶向治疗，增强非再生组织的可塑性和促进功能恢复。通过整合现有知识和识别关键知识空白，这项工作强调了表观遗传调节作为克服哺乳动物神经系统再生限制的治疗策略的变革潜力。

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引用次数: 0

Analysis of NOS3-786T>C and Intron 4 VNTR polymorphisms with respect to acute leukaemia risk in Algerian patients 阿尔及利亚患者NOS3-786T >c和内含子4 VNTR多态性与急性白血病风险的关系分析

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-04 DOI: 10.1016/j.genrep.2025.102404

N. Benhalilou , L.M. Berkani , Z.-E.-I. Lamraoui , F. Bouldjennet , N. Cherif , Z. Kaci , S. Louahchi , C. Touil-Boukoffa , R. Djidjik , R. Raache

Acute leukaemias are haematological neoplasms characterised by a steadily increasing incidence and high mortality, driven by the rapid proliferation of malignant blasts. Given that both the mechanisms of angiogenesis and the aetiology of these disorders remain poorly described and understudied in hematologic malignancies, we aimed to evaluate the potential role of polymorphisms in the endothelial nitric oxide synthase (NOS3) gene, both individually and in combination, on the risk and progression of acute leukaemia in Algerian patients.

To this end, we genotyped two NOS3 gene polymorphisms: the Intron 4 b/a/c variable number tandem repeat (VNTR) polymorphism (rs61722009) and the -786 T > C (rs2070744) promoter polymorphism in a cohort of 129 patients and 86 healthy controls. Genotyping was performed using agarose gel-based polymerase chain reaction PCR for VNTR polymorphism and polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) for the -786 T > C variant. Statistical analyses were conducted using Fisher's exact test or the Chi-squared (χ2) test and odds ratios (OR) with 95 % confidence intervals (CI) were calculated.

Our results revealed no significant difference in allelic or genotypic frequencies of the -786 T > C polymorphism between patients and controls (p > 0.05). In contrast, the frequency of the b/b genotype and the b allele of the VNTR polymorphism was significantly lower in patients than in healthy control (p = 0.004, OR = 0.37 and p = 0.002, OR = 0.41 respectively). Conversely, the a allele was significantly more frequent in patients (p = 0.011, OR = 2.13). Furthermore, combined genotype and haplotype analyses showed that the multilocus genotype TC/4b4b (p = 0.004, OR = 0.41) was overrepresented among controls, whereas the C-4a haplotype (p = 0.021, OR = 3.91) was more prevalent in patients.

These findings highlight the potential role of NOS3 gene polymorphisms in susceptibility to acute leukaemia. In particular, the intron 4 b/a/c VNTR polymorphism may serve as a genetic susceptibility marker. Moreover, the C-a haplotype, formed by the -786 T > C and intron 4 b/a/c variants, seems to be associated with an increased risk of disease progression, suggesting a possible synergistic effect between these polymorphisms.

急性白血病是一种血液学肿瘤，其特点是由恶性细胞的快速增殖引起的发病率和死亡率稳步上升。鉴于血管生成的机制和这些疾病的病因学在血液恶性肿瘤中仍然缺乏描述和研究，我们的目的是评估内皮型一氧化氮合酶（NOS3）基因多态性的潜在作用，无论是单独的还是联合的，在阿尔及利亚患者急性白血病的风险和进展中。为此，我们对129名患者和86名健康对照者的两种NOS3基因多态性进行了基因分型：内含子4 b/a/c可变数串联重复（VNTR）多态性（rs61722009）和-786 T >； c启动子多态性（rs2070744）。采用琼脂糖凝胶为基础的聚合酶链反应PCR进行VNTR多态性和聚合酶链反应限制性片段长度多态性（PCR- rflp）对-786 T >； C变异进行基因分型。采用Fisher精确检验或χ2检验进行统计分析，计算95%置信区间（CI）的比值比（or）。我们的研究结果显示，患者和对照组之间-786 T >； C多态性的等位基因或基因型频率无显著差异（p > 0.05）。相比之下，患者VNTR多态性b/b基因型和b等位基因的频率显著低于健康对照组（p = 0.004, OR = 0.37和p = 0.002, OR = 0.41）。相反，a等位基因在患者中更常见（p = 0.011, OR = 2.13）。此外，基因型和单倍型联合分析显示，TC/4b4b多位点基因型（p = 0.004, OR = 0.41）在对照组中被过度代表，而C-4a单倍型（p = 0.021, OR = 3.91）在患者中更为普遍。这些发现强调了NOS3基因多态性在急性白血病易感性中的潜在作用。特别是，内含子4b /a/c VNTR多态性可能作为遗传易感性标记。此外，由-786 T >； C和内含子4 b/a/ C变体形成的C-a单倍型似乎与疾病进展风险增加有关，这表明这些多态性之间可能存在协同效应。

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引用次数: 0

The emerging role of mitochondrial transcription termination factors (MTERFs) in tumorigenesis and progression in cancers 线粒体转录终止因子（mterf）在肿瘤发生和癌症进展中的新作用

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-04 DOI: 10.1016/j.genrep.2025.102406

Jintao He , Yaru Lin , Wenbing Huang , Ximin Tang , Min Yu , Zifeng Ruan , Xingguo Liu , Zhengliang Li , Yanwen Wang , Wei Xiong

Mitochondrial transcription and its dysregulation are emerging as important factors in cancer biology, providing new insights into tumor metabolism and potential therapeutic targets. The protein family of human mitochondrial transcription termination factor (MTERF) is pivotal in controlling mitochondrial gene expression and oxidative phosphorylation (OXPHOS) activity. MTERF proteins impact mitochondrial metabolism and cell energy generation by regulating mtDNA replication, transcription, and involvement in assembling mitochondrial ribosomal subunits and synthesizing proteins. Growing research suggests that members of the MTERF family are crucial not just for regular cell function but also play a significant role in the onset and development of human cancers. The expression of these transcription factors is intimately linked to the growth, movement, and penetration of tumor cells, underscoring their possible significance in predicting clinical outcomes and treating cancer. Dysregulation of MTERFs directly leads to altered expression of mtDNA in cancer cells, resulting in cellular metabolic reprogramming and mitochondrial dysfunction. The article encapsulates the roles and fundamental processes of various MTERF family members across different tumor forms, seeking to lay a theoretical groundwork for additional studies on their involvement in tumor development, forecasting prognoses, and specific treatments.

线粒体转录及其失调正在成为癌症生物学中的重要因素，为肿瘤代谢和潜在的治疗靶点提供了新的见解。人线粒体转录终止因子（MTERF）蛋白家族在控制线粒体基因表达和氧化磷酸化（OXPHOS）活性方面起着关键作用。MTERF蛋白通过调节mtDNA复制、转录和参与线粒体核糖体亚基组装和蛋白质合成来影响线粒体代谢和细胞能量产生。越来越多的研究表明，MTERF家族的成员不仅对正常的细胞功能至关重要，而且在人类癌症的发生和发展中也起着重要作用。这些转录因子的表达与肿瘤细胞的生长、运动和渗透密切相关，强调了它们在预测临床结果和治疗癌症方面的可能意义。mterf的失调直接导致癌细胞中mtDNA的表达改变，导致细胞代谢重编程和线粒体功能障碍。本文概述了MTERF家族成员在不同肿瘤类型中的作用和基本过程，旨在为进一步研究MTERF家族成员在肿瘤发展、预测预后和特异性治疗中的作用奠定理论基础。

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引用次数: 0

Disruption of LINC00265/miR-101-3p axis using siRNA suppresses growth and promotes apoptosis in laryngeal cancer cells 使用siRNA破坏LINC00265/miR-101-3p轴抑制喉癌细胞的生长并促进细胞凋亡

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-04 DOI: 10.1016/j.genrep.2025.102405

Mohaddese Maghsudlu , Masoumeh Razipour , Elham Ghadami , Ebrahim Karimi , Elia Damavandi , Negin Saeedi , Farzad Yazdani Bioki , Majid Kabuli , Mohsen Ghadami

Background

Laryngeal cancer is a prevalent malignancy of the head and neck, often associated with poor prognosis due to late diagnosis and therapeutic resistance. Emerging evidence highlights the important role of long non-coding RNAs (lncRNAs) in cancer progression, including LINC00265, which has been implicated in promoting tumor growth and metastasis in various cancers. Conversely, miR-101 functions as a tumor suppressor by targeting oncogenic pathways. Understanding the regulatory interaction between LINC00265 and miR-101 can provide new insights into disease biology.

Methods

We evaluated LINC00265 expression in 30 paired LSCC and adjacent normal tissues using qRT-PCR, which was followed by analyzing its correlation with clinicopathological features. To investigate LINC00265 functional effects, HN5 cells were transfected with LINC00265-specific siRNA, and afterward, cell viability and apoptosis were assessed through MTT assay and Annexin V/PI flow cytometry, respectively.

Results

Our results showed that LINC00265 was significantly overexpressed in LSCC tissues (2.52-fold increase, p < 0.0129), which was correlated with larger tumor size and lymph node metastasis. Moderate diagnostic accuracy for metastasis detection was demonstrated by ROC analysis (AUC = 0.74, p = 0.0276). Moreover, the knockdown of LINC00265 in HN5 cells significantly reduced cell viability by 30 %, and increased apoptosis up to 36.03 % potentially through upregulation of miR-101 (1.53-fold, p = 0.0012).

Discussion

Our study proposes that LINC00265 might exert an oncogenic effect in LSCC by promoting tumor progression, potentially through miR-101 suppression. Its association with metastasis and larger tumor size suggests clinical relevance as a prognostic biomarker. The knockdown of LINC00265 demonstrated anti-proliferative and pro-apoptotic effects that could suggest its therapeutic potential for LSCC treatment.

背景喉癌是一种常见的头颈部恶性肿瘤，由于诊断较晚和治疗耐药，预后较差。新出现的证据强调了长链非编码rna （lncRNAs）在癌症进展中的重要作用，包括在多种癌症中促进肿瘤生长和转移的LINC00265。相反，miR-101通过靶向致癌途径发挥肿瘤抑制作用。了解LINC00265和miR-101之间的调控相互作用可以为疾病生物学提供新的见解。方法采用qRT-PCR方法检测LINC00265在30对LSCC及其邻近正常组织中的表达，并分析其与临床病理特征的相关性。为了研究LINC00265对HN5细胞的功能影响，我们用LINC00265特异性siRNA转染HN5细胞，然后分别用MTT法和Annexin V/PI流式细胞术检测细胞活力和凋亡情况。结果我们的研究结果显示，LINC00265在LSCC组织中显著过表达（升高2.52倍，p < 0.0129），且与肿瘤大小增大、淋巴结转移相关。ROC分析显示转移检测的诊断准确度中等（AUC = 0.74, p = 0.0276）。此外，在HN5细胞中，LINC00265的敲低显著降低了30%的细胞活力，并可能通过上调miR-101使凋亡增加36.03%（1.53倍，p = 0.0012）。我们的研究表明，LINC00265可能通过抑制miR-101促进肿瘤进展，从而在LSCC中发挥致瘤作用。其与肿瘤转移和较大肿瘤大小的相关性提示其作为预后生物标志物具有临床意义。LINC00265的敲低显示出抗增殖和促凋亡的作用，这可能表明其治疗LSCC的潜力。

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引用次数: 0

An update on TWEAK/Fn14 signaling pathway: A comprehensive review TWEAK/Fn14信号通路的最新进展：综述

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-03 DOI: 10.1016/j.genrep.2025.102403

Ujjawal Sharma , Arpit Mehrotra , Bunty Sharma , Abhilasha Sood , Kartin Sak , Shafiul Haque , Nidarshana Chaturvedi Parashar , Madhu Gupta , Hardeep Singh Tuli

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional protein, present in various cell types and tissues, which, upon binding to the receptor factor-inducible 14 (Fn14), is involved in diverse pathologic processes including cell proliferation and death, angiogenesis, carcinogenesis, and inflammation. Interestingly, any alterations of their intracellular signaling are well correlated with the advancement of several diseases. The expression of TWEAK and Fn14 is augmented in many solid tumors compared with healthy tissues, thus leading to the enhancement of the proliferation, invasion, and subsequent migration of tumor cells. However, few TWEAK/Fn14 targeting pharmacological agents involved in inhibiting the progression of tumors have shown initial success in both clinical and pre-clinical experimental settings. Moreover, such agents improved angiogenesis, pro-inflammatory cytokine expression, and epithelial–mesenchymal transitions, upon TWEAK/Fn14 activation. This review provides an overview of the current understanding of the TWEAK–Fn14 signaling axis, its role in augmenting pathological characteristics of various diseases, and the existence of potential therapeutic targets for the development of novel pharmacological interventions.

肿瘤坏死因子样细胞凋亡弱诱导剂（TWEAK）是一种多功能蛋白，存在于多种细胞类型和组织中，与受体因子诱导14 （Fn14）结合后，参与多种病理过程，包括细胞增殖和死亡、血管生成、癌变和炎症。有趣的是，它们细胞内信号的任何改变都与几种疾病的进展密切相关。与健康组织相比，在许多实体瘤中，TWEAK和Fn14的表达增强，从而导致肿瘤细胞的增殖、侵袭和随后的迁移增强。然而，很少有针对TWEAK/Fn14的药物参与抑制肿瘤进展，在临床和临床前实验环境中都显示出初步的成功。此外，在TWEAK/Fn14激活后，这些药物可改善血管生成、促炎细胞因子表达和上皮-间质转化。本文综述了目前对TWEAK-Fn14信号轴的理解，其在增强各种疾病病理特征中的作用，以及开发新型药物干预的潜在治疗靶点。

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引用次数: 0

Mechanistic basis of NMN and rapamycin in aging biology: Independent and intersecting pathways NMN和雷帕霉素在衰老生物学中的机制基础：独立和交叉的途径

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-03 DOI: 10.1016/j.genrep.2025.102401

C. Sasidhar , V. Chitra , V. Naveen Kumar

Aging is a worldwide concern as populations are growing old, and there is increasing demand to find effective interventions capable of delaying the effects of age and thereby increasing healthspan. Nicotinamide mononucleotide (NMN) and rapamycin are two mechanistically different but potentially synergistic agents that target major hallmarks of aging, as part of emerging geroprotective. NMN is a precursor of NAD⁺, which activates sirtuins, maintains genomic stability, promotes mitochondrial activity; whereas rapamycin prevents activation of mTORC1 signaling through supporting autophagy and restricting cellular senescence and regulating immune response. This review has critically discussed the pharmacological molecular mechanism of NMN and rapamycin and their potential benefits in aging-associated pathways and preclinical and early clinical trials. We analyze the cross-communication between the NAD⁺/sirtuin and mTOR/autophagy axes, paying attention to the possibility of complementary regulation of the two systems to deliver synergistic effects against aging. Compared to other drugs that can be described as geroprotectors, including metformin, resveratrol, spermidine, and senolytics, NMN and rapamycin offer complementary mechanisms of action in a broader therapeutic context. To validate that this dual-pathway approach is safe and effective, we finally enumerate the challenges of translation dosing optimisation, biomarker development, and regulatory challenges. The association between NMN and rapamycin has shown a potential future in anti-aging medicine, as it has the potential to transform the paradigm of age-related disease therapy.

随着人口日益老龄化，老龄化是全世界关注的问题，因此越来越需要找到能够延缓年龄影响从而延长健康寿命的有效干预措施。烟酰胺单核苷酸（NMN）和雷帕霉素是两种机制不同但潜在协同作用的药物，它们针对衰老的主要标志，作为新兴的老年保护药物的一部分。NMN是NAD+的前体，NAD+激活sirtuins，维持基因组稳定性，促进线粒体活性；而雷帕霉素通过支持自噬、限制细胞衰老和调节免疫反应来阻止mTORC1信号的激活。这篇综述批判性地讨论了NMN和雷帕霉素的药理学分子机制及其在衰老相关途径和临床前和早期临床试验中的潜在益处。我们分析了NAD+/sirtuin和mTOR/自噬轴之间的交叉通讯，并关注了这两个系统互补调控以提供协同抗衰老效应的可能性。与二甲双胍、白藜芦醇、亚精胺和抗衰老药等其他可被描述为老年保护药物的药物相比，NMN和雷帕霉素在更广泛的治疗背景下提供了互补的作用机制。为了验证这种双通路方法的安全性和有效性，我们最后列举了翻译剂量优化、生物标志物开发和监管挑战。NMN和雷帕霉素之间的关联在抗衰老药物中显示出潜在的未来，因为它有可能改变年龄相关疾病治疗的范式。

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引用次数: 0

From microbes to medicine: How microbiota profiling is shaping the future of cancer therapy 从微生物到医学：微生物群分析如何塑造癌症治疗的未来

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-03 DOI: 10.1016/j.genrep.2025.102402

Anna Abdolshahi , Ramtin Naderian , Hamed Tahmasebi , Elham Paraandavaji , Mohammad Amin Hemmati , Setayesh Kashanipoor , Majid Eslami

Microbiota profiling is increasingly recognized as fundamental in advancing personalized cancer therapy. Beyond identifying microbial biomarkers, this review positions microbiota profiling as a dynamic and functional axis in precision oncology capable of both informing patient stratification and being therapeutically modulated to enhance treatment efficacy. By uncovering the dynamics of host-microbiota interactions, it sheds light on their impact on carcinogenesis, tumor progression, and treatment outcomes. This review synthesizes the latest advancements, ongoing challenges, and future directions for microbiome-based strategies in cancer treatment. This study adopts a narrative review approach, synthesizing findings from peer-reviewed articles indexed in PubMed, Web of Science, and Scopus, using a focused search strategy, as detailed in the methodology. The focus centers on microbiota profiling, its roles in cancer therapy, and related therapeutic implications. Microbiota profiling facilitates detailed characterization of microbial ecosystems and their involvement in cancer development and treatment. The next-generation sequencing, metabolomics, and machine learning have enhanced the discovery of microbial biomarkers. Emerging microbiota-focused interventions, including fecal microbiota transplantation and probiotic therapies, show promise in improving responses to immunotherapy and chemotherapy. However, clinical implementation faces hurdles such as interindividual variability, lack of standardization, and ethical complexities. Microbiota profiling represents a revolution for personalizing cancer treatments. This review synthesizes recent advances in microbiome-focused analytical technologies and examines their implications for cancer diagnosis, treatment, and immune modulation, highlighting key translational opportunities and future directions in oncology.

微生物群分析越来越被认为是推进个性化癌症治疗的基础。除了识别微生物生物标志物，本综述将微生物群分析定位为精确肿瘤学的动态和功能轴，既能告知患者分层，又能进行治疗调节，以提高治疗效果。通过揭示宿主-微生物群相互作用的动力学，它揭示了它们对致癌、肿瘤进展和治疗结果的影响。本文综述了基于微生物组的癌症治疗策略的最新进展、面临的挑战和未来方向。本研究采用叙述性综述方法，综合了PubMed、Web of Science和Scopus中检索的同行评议文章的发现，使用了重点搜索策略，详见方法论。重点是微生物群分析，它在癌症治疗中的作用，以及相关的治疗意义。微生物群分析有助于微生物生态系统的详细表征及其在癌症发展和治疗中的参与。下一代测序、代谢组学和机器学习促进了微生物生物标志物的发现。新兴的以微生物群为重点的干预措施，包括粪便微生物群移植和益生菌治疗，显示出改善免疫治疗和化疗反应的希望。然而，临床实施面临着个体间差异、缺乏标准化和伦理复杂性等障碍。微生物群分析代表了个性化癌症治疗的一场革命。本文综述了以微生物组为中心的分析技术的最新进展，并探讨了它们对癌症诊断、治疗和免疫调节的影响，强调了肿瘤领域的关键转化机会和未来方向。

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引用次数: 0

Association between Wnt signaling-related gene expression and clinical features in Iranian colorectal cancer patients: A potential diagnostic insight 伊朗结直肠癌患者Wnt信号相关基因表达与临床特征之间的关系：一种潜在的诊断见解

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-02 DOI: 10.1016/j.genrep.2025.102395

Mostafa Zargar , Ahdieh Hosseini Anvari , Mohammad Hadi Abbasian , Amir Hossein Alipour , Reza Shirkoohi , Shahla Mohammad Ganji

Aberrant activation of the Wnt signaling pathway plays a central oncogenic role in colorectal cancer (CRC). However, the expression profiles and clinical significance of multiple Wnt-related genes remain underexplored, particularly in specific populations such as Iranian patients. This study aimed to evaluate the expression of six key Wnt-associated genes and their associations with clinicopathological features in CRC tissues.

A case-control study was conducted using 40 advanced colorectal carcinoma tissues and 35 adjacent normal tissues obtained from Imam Khomeini Hospital, Tehran (2016–2017). Total RNA was extracted and reverse-transcribed, followed by quantitative real-time PCR. Gene expression levels were normalized to β-actin as the reference gene, and correlations with TNM staging parameters were analyzed statistically.

Five genes (HIF-1α, GSK3β, BCL9, CCND1, CDK1) were significantly upregulated in CRC tissues compared to normal controls (all P < 0.05), whereas MLH1 was downregulated (P = 0.052, borderline significance). MLH1 expression showed significant negative correlations with tumor stage, lymph node involvement (N), and metastasis (M) (all P = 0.02). GSK3β expression correlated with metastatic status (P = 0.002), BCL9 with tumor size (T) and nodal involvement (P < 0.05), and HIF-1α with tumor stage and nodal status (P < 0.05).

This multi-gene expression analysis reveals coordinated dysregulation of Wnt pathway components in CRC, with distinct correlation patterns linking specific genes to disease progression markers. These findings suggest potential applications in molecular staging and therapeutic targeting for Iranian CRC patients.

Wnt信号通路的异常激活在结直肠癌（CRC）中起中心致癌作用。然而，多种wnt相关基因的表达谱和临床意义仍未得到充分研究，特别是在伊朗患者等特定人群中。本研究旨在评估六个关键wnt相关基因在结直肠癌组织中的表达及其与临床病理特征的关系。采用2016-2017年在德黑兰伊玛目霍梅尼医院获得的40例晚期结直肠癌组织和35例邻近正常组织进行病例对照研究。提取总RNA逆转录，进行实时荧光定量PCR。将基因表达水平归一化，以β-肌动蛋白为参比基因，统计分析与TNM分期参数的相关性。5个基因（HIF-1α、GSK3β、BCL9、CCND1、CDK1）在结直肠癌组织中与正常对照组相比显著上调（均P <； 0.05），而MLH1下调（P = 0.052，有临界意义）。MLH1表达与肿瘤分期、淋巴结累及(N)、转移(M)呈显著负相关（均P = 0.02）。GSK3β表达与转移状态相关（P = 0.002）， BCL9表达与肿瘤大小(T)和淋巴结累及相关（P < 0.05）， HIF-1α表达与肿瘤分期和淋巴结状态相关（P < 0.05）。这项多基因表达分析揭示了CRC中Wnt通路组分的协同失调，并将特定基因与疾病进展标志物联系起来。这些发现提示了伊朗结直肠癌患者分子分期和治疗靶向的潜在应用。

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引用次数: 0

Caloric restriction modulates liver transcriptomes in an age-dependent manner in C57BL/6 N mice 在C57BL/6 N小鼠中，热量限制以年龄依赖的方式调节肝脏转录组

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-02 DOI: 10.1016/j.genrep.2025.102398

Lisha Wei , Yikai Huang , Junyi Zheng , Xuemin Xu , Jian Hong , Dehui Sun , Yanyan Zheng , Xiuke Ouyang

Caloric restriction (CR) is a well-established dietary intervention that promotes longevity and metabolic health; however, its age-dependent transcriptional effects on the liver remain unclear. Here, we aimed to delineate how CR remodels the hepatic transcriptome across 4, 9, 13, and 18 months of age in male C57BL/6 N mice and to determine whether the transcriptional response to CR is progressively attenuated in old age. We performed RNA sequencing on liver tissues from mice maintained on control or CR diets at 4, 9, 13, and 18 months of age to characterize transcriptional remodeling across aging.

Age was the primary determinant of global expression variance, whereas CR induced distinct, age-specific gene expression changes. The strongest responses occurred at 9 and 13 months, where CR upregulated genes related to circadian regulation, fatty acid metabolism, DNA replication, and repair, while suppressing inflammatory and lipogenic pathways. By 18 months, CR effects were attenuated, although circadian and metabolic signatures remained evident.

Functional enrichment analyses revealed consistent activation of PPARα-associated lipid metabolism, bile acid homeostasis, and circadian rhythm pathways, accompanied by repression of type I interferon-mediated immune signaling. Together, these findings show that CR elicits dynamic, age-dependent transcriptional reprogramming in the liver, enhancing metabolic and genomic maintenance programs in midlife (9–13 months) and dampening inflammatory responses, with reduced plasticity observed at 18 months. These findings suggest that CR exerts its strong and most multifaceted effects on hepatic metabolic and immune pathways in midlife, but that these transcriptional benefits become substantially blunted in old age, highlighting the importance of the timing of dietary interventions during the aging process.

热量限制（CR）是一种公认的促进长寿和代谢健康的饮食干预措施；然而，其对肝脏的年龄依赖性转录作用尚不清楚。在这里，我们的目的是描述CR如何在雄性C57BL/ 6n小鼠4、9、13和18个月大时重塑肝脏转录组，并确定CR的转录反应是否在老年时逐渐减弱。我们对4、9、13和18个月大的对照组或CR饮食小鼠的肝脏组织进行了RNA测序，以表征衰老过程中的转录重塑。年龄是整体表达差异的主要决定因素，而CR诱导明显的年龄特异性基因表达变化。最强的反应发生在9和13个月时，CR上调了与昼夜节律调节、脂肪酸代谢、DNA复制和修复相关的基因，同时抑制了炎症和脂肪生成途径。到18个月时，CR效应减弱，但昼夜节律和代谢特征仍然明显。功能富集分析显示，ppar α相关的脂质代谢、胆汁酸稳态和昼夜节律通路的激活一致，同时伴有I型干扰素介导的免疫信号的抑制。总之，这些发现表明，CR在肝脏中引发了动态的、年龄依赖性的转录重编程，增强了中年（9-13个月）的代谢和基因组维持程序，并抑制了炎症反应，在18个月时观察到可塑性降低。这些研究结果表明，CR在中年时对肝脏代谢和免疫途径产生强大且多方面的影响，但这些转录益处在老年时基本上变得钝化，突出了衰老过程中饮食干预时机的重要性。

{"title":"Caloric restriction modulates liver transcriptomes in an age-dependent manner in C57BL/6 N mice","authors":"Lisha Wei , Yikai Huang , Junyi Zheng , Xuemin Xu , Jian Hong , Dehui Sun , Yanyan Zheng , Xiuke Ouyang","doi":"10.1016/j.genrep.2025.102398","DOIUrl":"10.1016/j.genrep.2025.102398","url":null,"abstract":"<div><div>Caloric restriction (CR) is a well-established dietary intervention that promotes longevity and metabolic health; however, its age-dependent transcriptional effects on the liver remain unclear. Here, we aimed to delineate how CR remodels the hepatic transcriptome across 4, 9, 13, and 18 months of age in male C57BL/6 N mice and to determine whether the transcriptional response to CR is progressively attenuated in old age. We performed RNA sequencing on liver tissues from mice maintained on control or CR diets at 4, 9, 13, and 18 months of age to characterize transcriptional remodeling across aging.</div><div>Age was the primary determinant of global expression variance, whereas CR induced distinct, age-specific gene expression changes. The strongest responses occurred at 9 and 13 months, where CR upregulated genes related to circadian regulation, fatty acid metabolism, DNA replication, and repair, while suppressing inflammatory and lipogenic pathways. By 18 months, CR effects were attenuated, although circadian and metabolic signatures remained evident.</div><div>Functional enrichment analyses revealed consistent activation of PPARα-associated lipid metabolism, bile acid homeostasis, and circadian rhythm pathways, accompanied by repression of type I interferon-mediated immune signaling. Together, these findings show that CR elicits dynamic, age-dependent transcriptional reprogramming in the liver, enhancing metabolic and genomic maintenance programs in midlife (9–13 months) and dampening inflammatory responses, with reduced plasticity observed at 18 months. These findings suggest that CR exerts its strong and most multifaceted effects on hepatic metabolic and immune pathways in midlife, but that these transcriptional benefits become substantially blunted in old age, highlighting the importance of the timing of dietary interventions during the aging process.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102398"},"PeriodicalIF":0.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PGK1 is a prognostic molecule and silencing PGK1 inhibits the growth in breast cancer cells PGK1是一种预后分子，沉默PGK1可抑制乳腺癌细胞的生长

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-11-27 DOI: 10.1016/j.genrep.2025.102396

Zhenzhen Yang , Ying Han

Background

Due to its persistently high prevalence and mortality, breast cancer (BC) remains a significant public health challenge. The present study comprehensively investigates the role of PGK1 (Phosphoglycerate Kinase 1) in BC, recognizing its critical involvement in tumorigenesis and disease progression despite the scarcity of reports addressing its specific implications.

Methods

Genomic microarray datasets and associated clinicopathological records were acquired from two publicly accessible repositories: the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Comprehensive comparative investigations were conducted, covering functional enrichment evaluation, characterization of the tumor immune microenvironment, and assessment of pharmacological responsiveness in BC. Experimental validation of PGK1's biological functions in BC was further carried out using both in vitro experimental models and in vivo animal systems. Statistical processing and graphical representations of data were primarily executed using the R programming environment.

Results

Experimental results revealed a marked elevation in PGK1 expression levels within BC tissues, correlating with unfavorable clinical outcomes. Clinical association studies identified substantial relationships between PGK1 abundance and critical pathological markers in BC, such as estrogen receptor (ER) positivity, progesterone receptor (PR) status, and human epidermal growth factor receptor 2 (Her-2) expression levels. Gene Set Enrichment Analysis (GSEA) demonstrated PGK1's prominent engagement in fundamental cellular mechanisms, particularly mitotic regulation and genomic replication processes. Additionally, systematic evaluation revealed significant co-variation patterns between PGK1 and immune checkpoint regulators. Pharmacogenomic assessments established proportional relationships between PGK1 expression and therapeutic responses to specific agents, including AT-7519, Methotrexate, and MS-275. In cell experiments, silencing PGK1 resulted in a marked decrease in cellular proliferation and migration abilities, accompanied by an increase in apoptosis levels. In nude mouse tumorigenesis experiments, PGK1 knockdown significantly slowed tumor growth. Overall, both in vitro and in vivo results demonstrate that reduced PGK1 expression markedly affects BC cell growth.

Conclusions

This study systematically validates PGK1's prognostic value, clinical associations, and functional relevance in BC, while integrating multi-omics data (transcriptomic, clinical, immune, and pharmacogenomic) to clarify its subtype-specific roles. The findings might position PGK1 as a high-priority therapeutic candidate for targeted intervention strategies against breast malignancies.

由于其持续的高患病率和死亡率，乳腺癌（BC）仍然是一个重大的公共卫生挑战。本研究全面调查了PGK1（磷酸甘油酸激酶1）在BC中的作用，认识到它在肿瘤发生和疾病进展中的关键作用，尽管缺乏关于其具体含义的报道。方法从癌症基因组图谱（TCGA）和基因表达图谱（GEO）这两个可公开访问的数据库中获取基因组微阵列数据集和相关临床病理记录。我们进行了全面的比较研究，包括功能富集评价、肿瘤免疫微环境的表征和BC的药理反应性评估。通过体外实验模型和体内动物系统进一步验证PGK1在BC中的生物学功能。统计处理和数据的图形化表示主要使用R编程环境执行。结果实验结果显示，BC组织中PGK1表达水平显著升高，与不利的临床结果相关。临床关联研究发现，PGK1丰度与BC的关键病理标志物（如雌激素受体（ER）阳性、孕激素受体（PR）状态和人表皮生长因子受体2 （Her-2）表达水平）之间存在实质性关系。基因集富集分析（GSEA）表明，PGK1在基本细胞机制，特别是有丝分裂调节和基因组复制过程中发挥着重要作用。此外，系统评估揭示了PGK1和免疫检查点调节因子之间显著的共变异模式。药物基因组学评估确定了PGK1表达与对特定药物（包括AT-7519、甲氨蝶呤和MS-275）的治疗反应之间的比例关系。在细胞实验中，沉默PGK1导致细胞增殖和迁移能力明显下降，并伴有凋亡水平升高。在裸鼠肿瘤发生实验中，PGK1敲低可显著减缓肿瘤生长。总的来说，体外和体内的结果都表明，PGK1表达的降低显著影响BC细胞的生长。本研究系统地验证了PGK1在BC中的预后价值、临床关联和功能相关性，同时整合了多组学数据（转录组学、临床、免疫和药物基因组学）来阐明其亚型特异性作用。这些发现可能将PGK1定位为针对乳腺恶性肿瘤的靶向干预策略的高优先级治疗候选者。

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引用次数: 0