Gene Reports最新文献_第6页

The expressions of nr0b1/2 genes in the Chinese giant salamander and their response to estradiol benzoate/17α-methyltestosterone treatment 中国大鲵 nr0b1/2 基因的表达及其对苯甲酸雌二醇/17α-甲基睾酮处理的反应

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-26 DOI: 10.1016/j.genrep.2024.102045

Han Yang , Xuerong Sun , Lishan Xu, Shijun Yang, Fan Yan, Guangxiang Zhu, Yanzhi Jiang, Huailiang Xu, Jiayun Wu, Anxiang Wen, Meng Xie, Xue Liu, Qin Wang

Previously, the nr0b1 and nr0b2 genes have been identified in various animals and found to be closely associated with sex determination. In order to investigate the regulatory roles of nr0b1 and nr0b2 genes in the sex determination of Chinese giant salamander (CGS, Andrias davidianus), we obtained the full-length cDNA sequences of nr0b1 and nr0b2 through cloning, determined the characteristics of their tissue expressions and the responses of nr0b1 and nr0b2 to estradiol benzoate (EB) and 17α-methyltestosterone (MT) by using quantitative real-time PCR (qRT-PCR), and evaluated gonad development through histological sections. The full-lengths of cDNA of nr0b1/2 in CGS are separately 1278bp and 789bp. They have complete open reading frames (ORF) of 864bp and 774bp and encode 287 and 257 amino acids respectively. The 3' untranslated regions (UTR) are 276bp and 15bp, and the 5' UTR of nr0b1 is 138bp. In the 3' UTR of nr0b1, a putative polyadenylation signal (AATAAA) is identified. Tissue distribution analysis indicates that nr0b1 is mainly expressed in the pituitary, kidney, and testes, with significant differences between females (ZW-F) and males (ZZ-M) expression in the testes. On the other hand, nr0b2 is mainly expressed in the liver, followed by gonadal tissues. After immersion and feeding with EB and MT, EB's promotion on nr0b1 expression in CGS ovaries and testes is shown, by contrast MT only has a positive effect on nr0b2 in CGS testes. Histological sections show that after EB treatment, both genetic females (ZW-F) and sex-reversed females (ZZ-F) of CGS contain oogonia, indicating that EB can cause sex reversal in CGS; however, after MT treatment, no cellular morphological changes are observed either in genetic females (ZW-F) or in genetic males (ZW-M), indicating that this concentration cannot induce a shift in the sex ratio of CGS. These findings lay the foundation for further investigating the molecular mechanisms by which nr0b1/2 influence the differentiation and maintenance of CGS gonads.

此前，nr0b1和nr0b2基因已在多种动物中被发现并与性别决定密切相关。为了研究nr0b1和nr0b2基因在中国大鲵性别决定中的调控作用，我们通过克隆获得了nr0b1和nr0b2的全长cDNA序列、利用实时定量 PCR（qRT-PCR）技术测定了它们的组织表达特征以及 nr0b1 和 nr0b2 对苯甲酸雌二醇（EB）和 17α-甲基睾酮（MT）的反应，并通过组织切片评估了性腺的发育情况。CGS中nr0b1/2的cDNA全长分别为1278bp和789bp。它们的完整开放阅读框（ORF）分别为 864bp 和 774bp，分别编码 287 和 257 个氨基酸。3' 非翻译区（UTR）分别为 276bp 和 15bp，nr0b1 的 5' UTR 为 138bp。在 nr0b1 的 3' UTR 中，发现了一个假定的多聚腺苷酸化信号（AATAAA）。组织分布分析表明，nr0b1 主要在垂体、肾脏和睾丸中表达，雌性（ZW-F）和雄性（ZZ-M）在睾丸中的表达存在显著差异。另一方面，nr0b2 主要在肝脏中表达，其次是性腺组织。浸泡和喂食 EB 和 MT 后，EB 对 CGS 卵巢和睾丸中 nr0b1 的表达有促进作用，相反 MT 只对 CGS 睾丸中 nr0b2 有积极影响。组织学切片显示，EB处理后，CGS的遗传雌性（ZW-F）和性别逆转雌性（ZZ-F）都含有卵原细胞，表明EB能引起CGS的性别逆转；但MT处理后，遗传雌性（ZW-F）和遗传雄性（ZW-M）都未观察到细胞形态变化，表明该浓度不能诱导CGS性别比例的改变。这些发现为进一步研究 nr0b1/2 影响 CGS 性腺分化和维持的分子机制奠定了基础。

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引用次数: 0

MicroRNA-506 as a tumor suppressor in prostate cancer by regulation of Hippo signaling pathway MicroRNA-506 通过调控 Hippo 信号通路成为前列腺癌的肿瘤抑制因子

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-26 DOI: 10.1016/j.genrep.2024.102047

Amir Sadra Zangouei , Zahra Nasrpour Navaei , Fatemeh Taghavinia , Mohammad Reza Abbaszadegan , Meysam Moghbeli

Introduction

Prostate cancer (PCa) is considered as one of the leading causes of cancer related deaths among males globally. There is a high rate of tumor relapse and metastasis in PCa patients that is associated with chemo-resistance. Beside the elimination of tumor cells, chemotherapy has an adverse effect in normal cells. Therefore, it is required to clarify the molecular tumor biology to introduce novel markers to predict the drug response in PCa patients. Hippo signaling pathway is an important regulator of cell proliferation, migration, and drug response that can be modulated by microRNAs (miRNAs). Since, miR-506 deregulation has been reported in PCs, in the present study we assessed a probable role of miR-506 in regulation of Hippo signaling pathway during prostate tumor cell migration and drug resistance.

Materials and methods

The mRNA expression levels of Hippo signaling components were assessed in miR-506 ectopic expressed in comparison with control PC3 cells. Apoptosis assay, drug response, and cell migration were also assessed to find the role of miR-506 in prostate tumor cell aggressiveness.

Results

MiR-506 promoted the Hippo signaling pathway via TAZ and CTGF up regulations, while BIRC5, FAT, and C-MYC down regulations in PC3 cells. MiR-506 significantly reduced prostate tumor cell migration (p = 0.019) and Paclitaxel (TXL) resistance (p = 0.0006), while promoted apoptosis (p < 0.0001).

Conclusion

miR-506 exerted a tumor suppressor role during PCa progression by activation of Hippo pathway. MiR-506 targeted the FAT to activate the YAP/TAZ and nuclear translocation where it can bind with TEAD to up regulate the CTGF that resulted in reduced PCa cell migration. The WNT inhibition and C-MYC down regulation by the CTGF resulted in BIRC5 down regulation that induced apoptosis in PCa cells. Therefore, miR-506 can be introduced as a therapeutic marker in PCa following the confirmation by the animal studies and further clinical trials.

导言前列腺癌（PCa）被认为是全球男性因癌症死亡的主要原因之一。前列腺癌患者的肿瘤复发率和转移率很高，这与化疗耐药性有关。化疗除了能消灭肿瘤细胞外，还会对正常细胞产生不良影响。因此，需要阐明肿瘤分子生物学，引入新的标记物来预测 PCa 患者的药物反应。Hippo信号通路是细胞增殖、迁移和药物反应的重要调节因子，可被微RNA（miRNA）调节。由于 miR-506 在 PCs 中的失调已有报道，在本研究中，我们评估了 miR-506 在前列腺肿瘤细胞迁移和耐药性过程中调控 Hippo 信号通路的可能作用。结果miR-506通过TAZ和CTGF上调，而BIRC5、FAT和C-MYC下调促进了PC3细胞中的Hippo信号通路。MiR-506 通过激活 Hippo 通路，在 PCa 进展过程中发挥抑瘤作用。MiR-506以FAT为靶点激活YAP/TAZ，并进行核转位，与TEAD结合，上调CTGF，从而减少PCa细胞的迁移。CTGF 对 WNT 的抑制和 C-MYC 的下调导致了 BIRC5 的下调，从而诱导了 PCa 细胞的凋亡。因此，在动物实验和进一步的临床试验证实后，miR-506 可以作为治疗 PCa 的标志物。

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引用次数: 0

DICER1 rs3742330 and AGO1 rs636832 polymorphisms and acute lymphoblastic leukemia in Greek children and adolescents: A case-control study 希腊儿童和青少年中的 DICER1 rs3742330 和 AGO1 rs636832 多态性与急性淋巴细胞白血病：病例对照研究

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-24 DOI: 10.1016/j.genrep.2024.102043

Ioannis Kyriakidis , Iordanis Pelagiadis , Nikolaos Katzilakis , Maria Stratigaki , Ioanna Keklikoglou , Athanasios Tragiannidis , Eftichia Stiakaki

引用次数: 0

Comparative genome composition of two closely related biocontrol strains of Bacillus velezensis endophytes 两种密切相关的内生芽孢杆菌生物控制菌株的基因组组成比较

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-24 DOI: 10.1016/j.genrep.2024.102036

Kazeem A. Alayande, Ivan Schutte, Prudent Mokgokong, Rasheed Adeleke

Comparative genomics was carried out between Bacillus velezensis KV10 and KV15 endophytes isolated from Elytropappus rhinocerotis. The nucleotides from the isolates were sequenced on an Illumina platform and assembled using SPAdes. Taxonomical identification was determined by a measure of evolutionary distance and codon-based phylogenetic trees. Sequence alignment against a representative isolate was assessed with Mauve, and a unique genomic region was determined through genome BLAST against a representative strain using GView. Protein family sorter and comparative pathway tools assigned to RASTtk4 were used to align the shared proteins between the isolates. antiSMASH was used to identify gene clusters for the bioactive secondary metabolites. Identification of mutant variants was determined through SNP calling using BWA-MEM to align the reads and FreeBayes for high-quality variants. B. velezensis KV10 and KV15 have genome sizes of 3,992,370 bp and 3,880,685 bp, and GC contents of 46.37 % and 46.49 %, respectively. There are identified genetic and evolutionary dissimilarities between the two endophytic isolates. Nineteen proteins with well-defined functions were found unique to KV10, while a total of thirty-two proteins were found unique to KV15. Missense or synonymous point mutations were observed at different loci in the KV10 genome; all affected codons are involved in the formation of polyketide synthase and general stress protein (YdbA and YdbB). The affected genes by point mutations in the KV15 are YeeF and FliK. Both strains contain gene clusters putative for biosynthesis of specific antimicrobial metabolites such as difficidin, macrolactin, fengycin, bacillibactin, bacillaene, and bacilysin. While only KV10 has additional gene clusters for mersacidin and surfactin biosynthesis. In addition, biosynthetic metabolites extracted from both strains exhibited notable antimicrobial effectiveness against test Serratia marcescens and Fusarium sp. Both isolates exhibit putative genetic features and are supported by in vitro assessment as promising candidates for biocontrol agents.

对从犀牛(Elytropappus rhinocerotis)体内分离出的枯草芽孢杆菌(Bacillus velezensis KV10)和枯草芽孢杆菌(Bacillus velezensis KV15)进行了基因组学比较。在 Illumina 平台上对分离物的核苷酸进行了测序，并使用 SPAdes 进行了组装。通过进化距离和基于密码子的系统发生树来确定分类鉴定。使用 Mauve 评估了与代表性分离株的序列比对，并使用 GView 通过与代表性菌株的基因组 BLAST 确定了独特的基因组区域。使用分配给 RASTtk4 的蛋白质家族筛选器和比较途径工具对分离株之间的共有蛋白质进行比对。使用 BWA-MEM 对读数进行比对，并使用 FreeBayes 对高质量变体进行 SNP 调用，从而确定突变变体。B. velezensis KV10 和 KV15 的基因组大小分别为 3,992,370 bp 和 3,880,685 bp，GC 含量分别为 46.37 % 和 46.49 %。这两种内生分离物在遗传和进化方面存在明显的差异。在 KV10 中发现了 19 种具有明确功能的独特蛋白质，而在 KV15 中则发现了 32 种独特蛋白质。在 KV10 基因组的不同位点上发现了错义或同义点突变；所有受影响的密码子都参与了多酮合成酶和一般应激蛋白（YdbA 和 YdbB）的形成。在 KV15 中，受点突变影响的基因是 YeeF 和 FliK。这两种菌株都含有可能用于生物合成特定抗菌代谢物的基因簇，如 difficidin、macrolactin、fengycin、bacillibactin、bacillaene 和 bacilysin。只有 KV10 有额外的基因簇，用于 mersacidin 和 surfactin 的生物合成。此外，从这两种菌株中提取的生物合成代谢物对测试的大豆沙雷氏菌（Serratia marcescens）和镰刀菌（Fusarium sp.

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引用次数: 0

Piperazine reveals as a cell wall targeting antifungal agent against Candida albicans 揭示哌嗪是一种针对白念珠菌细胞壁的抗真菌剂

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-24 DOI: 10.1016/j.genrep.2024.102044

Anubhuti Jha, Awanish Kumar

Candida albicans, a dimorphic opportunistic fungal pathogen, poses a significant threat to immunocompromised patients, with infections becoming increasingly severe due to the emergence of multi-drug resistance and the lack of effective treatments. This study investigates the antifungal properties of piperazine, a heterocyclic organic compound, and its mechanism of action against Candida species. In silico molecular docking, analysis was conducted to evaluate the interaction between piperazine and cell wall synthesis proteins, complemented by pharmacokinetic ADMET studies to assess its potential as a drug candidate. The minimum inhibitory concentration for eight Candida species ranged from 256 to 512 μg/mL. Morphological changes in C. albicans treated with piperazine were observed using scanning electron microscopy, revealing significant cell wall damage. Our findings suggest that piperazine could serve as a potential cell wall-targeting antifungal agent, potentially expanding the current arsenal of antifungal therapies.

白色念珠菌是一种二形机会性真菌病原体，对免疫力低下的患者构成严重威胁，由于出现多重耐药性和缺乏有效的治疗方法，感染变得越来越严重。本研究探讨了杂环有机化合物哌嗪的抗真菌特性及其对念珠菌的作用机制。研究人员进行了分子对接分析，以评估哌嗪与细胞壁合成蛋白之间的相互作用，并辅以药代动力学 ADMET 研究来评估其作为候选药物的潜力。八种念珠菌的最低抑制浓度介于 256 至 512 μg/mL 之间。使用扫描电子显微镜观察了用哌嗪处理过的白色念珠菌的形态变化，发现细胞壁受到了严重破坏。我们的研究结果表明，哌嗪可作为一种潜在的细胞壁靶向抗真菌剂，有可能扩展目前的抗真菌疗法。

引用次数: 0

Transcriptomic and metabolomic investigations of methyl jasmonate-mediated enhancement of low temperature stress resistance in Cassia obtusifolia L. 茉莉酸甲酯介导的决明子抗低温胁迫转录组学和代谢组学研究

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-22 DOI: 10.1016/j.genrep.2024.102040

Yue Zhang , Weiling Jiang , Abdullah, Biru Shi, Yuan Gao, Xia Yang, Zhimei Xing, Tingting Zhang, Lifeng Han, Xiaoxuan Tian

Low temperature stress negatively impacts plant growth and development, reducing crop yields by disrupting metabolite production and accumulation. Cassia obtusifolia L., a widely cultivated medicinal plant in subtropical regions, is particularly vulnerable to such stress. Methyl jasmonate (MeJA) regulates plant growth, defense mechanisms, and secondary metabolite production. This study investigated how C. obtusifolia responds to low temperature stress under MeJA treatment using transcriptomic and metabolomic approaches. MeJA treatment upregulated several transcription factor families, including APE/ERF-ERF, WRKY, NAC, and MYB-related, which modulated the plant's response to cold stress. These transcription factors influenced the expression of genes involved in glycolysis, sugar metabolism, and amino acid pathways, contributing to the plant's adaptive responses. Differentially expressed genes were associated with key metabolic processes such as flavonoid biosynthesis, ribosome function, glycolysis/gluconeogenesis, and sugar metabolism. Using H-NMR and LC-MS techniques, we observed that MeJA induced the accumulation of sugars and amino acids in the leaves of C. obtusifolia seedlings under cold stress, while levels of three flavonoid compounds Isoliquiritigenin, Kaempferol-7-O-glucoside, and Phloretin significantly decreased. Enrichment analysis indicated that MeJA modulates the biosynthetic pathways of these compounds in a dose-dependent manner. Integrating metabolomic and transcriptomic data further elucidated alterations in the flavonoid biosynthetic network and other metabolic pathways under low temperature stress. These findings offer insights into the molecular mechanisms underlying flavonoid synthesis and other metabolic adjustments in C. obtusifolia under MeJA treatment.

低温胁迫会对植物的生长和发育产生负面影响，通过破坏代谢产物的产生和积累而降低作物产量。决明子是亚热带地区广泛种植的药用植物，特别容易受到这种胁迫的影响。茉莉酸甲酯（MeJA）能调节植物的生长、防御机制和次生代谢物的产生。本研究采用转录组学和代谢组学方法，研究了在 MeJA 处理下 C. obtusifolia 如何应对低温胁迫。MeJA 处理可上调多个转录因子家族，包括 APE/ERF-ERF、WRKY、NAC 和 MYB 相关因子，从而调节植物对低温胁迫的响应。这些转录因子影响了参与糖酵解、糖代谢和氨基酸途径的基因的表达，促进了植物的适应性反应。差异表达的基因与黄酮类化合物生物合成、核糖体功能、糖酵解/糖醛酸生成和糖代谢等关键代谢过程有关。利用 H-NMR 和 LC-MS 技术，我们观察到 MeJA 诱导了冷胁迫下 C. obtusifolia 幼苗叶片中糖和氨基酸的积累，而三种黄酮类化合物 Isoliquiritigenin、Kaempferol-7-O-glucoside 和 Phloretin 的水平显著下降。富集分析表明，MeJA 以剂量依赖的方式调节了这些化合物的生物合成途径。整合代谢组和转录组数据进一步阐明了低温胁迫下类黄酮生物合成网络和其他代谢途径的变化。这些研究结果有助于深入了解在 MeJA 处理下 C. obtusifolia 中黄酮类化合物合成和其他代谢调整的分子机制。

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引用次数: 0

Genetic expression in cancer research: Challenges and complexity 癌症研究中的基因表达：挑战与复杂性

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-21 DOI: 10.1016/j.genrep.2024.102042

Hengrui Liu , Zheng Guo , Panpan Wang

Cancer research is profoundly influenced by the complex interplay of gene expression, yet conventional studies often emphasize genes with high expression levels, potentially overlooking those that contribute subtly to tumorigenesis. This review challenges the standard paradigms by questioning the direct causality often attributed to high gene expression in cancer progression and underscores the importance of distinguishing correlation from causation. It highlights how traditional bulk data analysis might mask crucial cell-specific gene activities, a limitation increasingly addressed by emerging single-cell and spatial transcriptomics, albeit with their own inherent challenges. Additionally, the review delves into the critical roles of both oncogenes and tumor driver genes, advocating for a precise differentiation in research and therapy. Furthermore, it discusses the revolutionary impact of CRISPR technology in identifying essential genes for cancer cell survival, which, while crucial, may not necessarily drive cancer. The complexities of epigenetic regulation and the discrepancies between mRNA and protein expression levels are also explored, emphasizing the necessity for integrated approaches that combine transcriptomics, proteomics, and computational models. This integrated perspective is vital for developing targeted therapies that address the multifaceted nature of gene expression and its regulation in cancer, aiming to refine therapeutic strategies and enhance clinical outcomes.

癌症研究受到基因表达复杂相互作用的深刻影响，然而传统研究往往强调高表达水平的基因，却有可能忽略那些对肿瘤发生有微妙作用的基因。这篇综述挑战了标准范式，质疑了高基因表达在癌症进展中通常被归因于直接因果关系的说法，并强调了区分相关性和因果关系的重要性。它强调了传统的批量数据分析如何可能掩盖关键的细胞特异性基因活动，而新兴的单细胞和空间转录组学越来越多地解决了这一局限性，尽管它们也有其固有的挑战。此外，综述还深入探讨了致癌基因和肿瘤驱动基因的关键作用，主张在研究和治疗中进行精确区分。此外，综述还讨论了 CRISPR 技术在确定癌细胞存活的关键基因方面的革命性影响，这些基因虽然至关重要，但不一定会导致癌症。报告还探讨了表观遗传调控的复杂性以及 mRNA 和蛋白质表达水平之间的差异，强调了结合转录组学、蛋白质组学和计算模型的综合方法的必要性。这种综合视角对于开发靶向疗法至关重要，可解决癌症中基因表达及其调控的多面性问题，从而完善治疗策略，提高临床疗效。

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引用次数: 0

miR-16-5p may modulate migration and proliferation through TP53 and LncRNA-NEAT1 in triple-negative breast cancer miR-16-5p 可通过 TP53 和 LncRNA-NEAT1 调节三阴性乳腺癌的迁移和增殖

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-20 DOI: 10.1016/j.genrep.2024.102038

Qingtao Ni , Yida Qian , Tongbo Yi , Jian Zhou , Kai Sang , Chi Pan

Introduction

MicroRNAs (miRNAs) are potential candidate clinical biomarkers for many diseases. This study explored the role and potential mechanisms of miR-16-5p in triple-negative breast cancer (TNBC).

Results

The expression of miR-16-5p was lower in wax block sections obtained from 47 TNBC patient samples. Overexpression of miR-16-5p decreased the migratory abilities and the cell proliferation in MDA-MB-231 cells. We found miR-16-5p modulated TP53 and LncRNA-NEAT1 in bioinformatics analysis. In transfection experiments, the higher expression of lncRNA-NEAT1 and TP53 were observed in miR-16-5p inhibitor group.

Conclusion

Our data demonstrated that miR-16-5p was lowly expressed and acted as a tumor suppressor in TNBC. Moreover, miR-16-5p regulated TNBC cell proliferation and migratory capacity by modulating TP53 and lncRNA-NEAT1 in vitro.

导言微小RNA（miRNA）是许多疾病潜在的候选临床生物标记物。本研究探讨了 miR-16-5p 在三阴性乳腺癌（TNBC）中的作用和潜在机制。过表达 miR-16-5p 会降低 MDA-MB-231 细胞的迁移能力和细胞增殖。我们在生物信息学分析中发现，miR-16-5p 可调节 TP53 和 LncRNA-NEAT1。结论我们的数据表明，miR-16-5p 在 TNBC 中低表达，并作为肿瘤抑制因子发挥作用。此外，miR-16-5p 在体外通过调节 TP53 和 lncRNA-NEAT1 来调控 TNBC 细胞的增殖和迁移能力。

引用次数: 0

miR-98 and miR-629 can be used as a potential biomarker on relapsing-remitting multiple sclerosis patients miR-98 和 miR-629 可用作复发缓解型多发性硬化症患者的潜在生物标记物

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-19 DOI: 10.1016/j.genrep.2024.102041

Burçin Erkal Çam , Tuğba Elgün , Tuğba Kul Köprülü , Arzu Çoban , Şenay Vural Korkut

Introduction

Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), characterized by chronic inflammation, demyelination, and neurodegeneration. In recent years, among non-coding RNAs miRNA have emerged as key regulators of different biological processes and it has been suggested that they play an important role in the mechanisms underlying MS pathogenesis. Through in silico methods, miR-629-5p and miR-98-5p were identified as significant factors in MS pathology. The aim of this study was to examine the levels of expression of miR-629-5p and miR-98-5p in blood samples obtained from patients with relapsing–remitting MS. Methods: Total blood were recruited from RRMS and control group and qPCR analysis was used for evaluating of target miRNAs expression. The mirDIP database was utilized to identify the target genes. Hub genes were identified with the Cytoscape and target pathways were identified using the STRING. Results: Expression analysis revealed a significant upregulation of miR-629-5p and miR-98-5p (FC ≥ 1.5 and p < 0.05) in patients with RRMS. PI3K-Akt, Rap1, MAPK and FoxO signaling pathways were found as target. Discussion: The discovery of these miRNAs suggests that they may have a notable impact on MS patients by intervening on pathways involved in both the immune and nervous systems.

导言多发性硬化症（MS）是一种影响中枢神经系统（CNS）的自身免疫性疾病，以慢性炎症、脱髓鞘和神经变性为特征。近年来，在非编码 RNA 中，miRNA 已成为不同生物过程的关键调控因子，并被认为在多发性硬化症的发病机制中发挥着重要作用。通过硅学方法，miR-629-5p 和 miR-98-5p 被确定为多发性硬化症病理的重要因素。本研究旨在检测复发性多发性硬化症患者血液样本中 miR-629-5p 和 miR-98-5p 的表达水平。研究方法采集 RRMS 组和对照组患者的总血样，采用 qPCR 分析评估目标 miRNAs 的表达。利用 mirDIP 数据库确定靶基因。利用 Cytoscape 确定枢纽基因，利用 STRING 确定目标通路。结果显示表达分析表明，在 RRMS 患者中，miR-629-5p 和 miR-98-5p 表达明显上调（FC ≥ 1.5，p < 0.05）。PI3K-Akt、Rap1、MAPK和FoxO信号通路被认为是靶点。讨论这些 miRNAs 的发现表明，它们可能通过干预免疫系统和神经系统的通路对多发性硬化症患者产生显著影响。

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引用次数: 0

Circulating microRNAs as the achilles forte of diagnostics and prognostics in acute graft versus host disease following allogeneic hematopoietic stem cell transplantation 循环微RNA是异体造血干细胞移植后急性移植物抗宿主疾病诊断和预后的致命弱点

IF 1 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2024-09-19 DOI: 10.1016/j.genrep.2024.102037

Marzieh Izadifard , Mohammad Ahmadvand , Kamran Alimoghadam , Hossein Pashaiefar , Ghazal Seghatoleslami , Maryam Barkhordar , Marjan Yaghmaie

Acute graft-versus-host disease (aGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), a procedure intended to treat malignant and nonmalignant hematological illnesses. At this time, there are no laboratory tests that can accurately forecast the likelihood of developing aGVHD, a patient's response to treatment, or their chance of life. Encouragingly, specific microRNAs have demonstrated consistent connections with the onset, severity, and clinical consequences of aGVHD through their dysregulated expression patterns, providing potential advantages in patient management and individualized therapy plans. Additionally, minimally invasive diagnostic methods are made easier by identification and measurement of circulating microRNAs as biomarkers in bodily fluids such as blood or urine using high-throughput screening techniques like qPCR, microarray analysis, and next-generation sequencing. Regarding the diagnosis, prognosis, and therapeutic response, this review is concentrated on the most recent research that offer proof of the possible utility of circulating microRNAs in blood and other bodily fluids as minimally invasive biomarkers of aGVHD. In addition to being useful tools for enhancing aGVHD management and patient outcomes, microRNAs distinctive expression patterns and functions in disease biology also present prospects for personalized medicine.

急性移植物抗宿主疾病（aGVHD）是异基因造血干细胞移植（allo-HSCT）后常见的并发症，这种手术旨在治疗恶性和非恶性血液病。目前，还没有任何实验室检测方法可以准确预测罹患异基因造血干细胞抗宿主疾病的可能性、患者对治疗的反应或存活机会。令人鼓舞的是，特定的 microRNA 通过其失调的表达模式与 aGVHD 的发病、严重程度和临床后果有着一致的联系，为患者管理和个体化治疗计划提供了潜在的优势。此外，利用 qPCR、微阵列分析和新一代测序等高通量筛选技术对血液或尿液等体液中作为生物标志物的循环 microRNA 进行鉴定和测量，可使微创诊断方法变得更加简便。在诊断、预后和治疗反应方面，本综述集中于最新的研究，这些研究证明了血液和其他体液中的循环 microRNA 可作为 aGVHD 的微创生物标志物。microRNA 除了是改善 aGVHD 管理和患者预后的有用工具外，其在疾病生物学中独特的表达模式和功能也为个性化医疗带来了前景。

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引用次数: 0