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Investigation of cervical cell image segmentation technology based on deep learning and non-coding RNAs 基于深度学习和非编码rna的宫颈细胞图像分割技术研究
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-30 DOI: 10.1016/j.ncrna.2025.09.009
Cheng Cheng , Yi Yang , Youshan Qu

Background

Cervical cancer remains a significant health concern worldwide, necessitating effective diagnostic methods such as cervical cell image segmentation. This review outlines the challenges and importance of accurately segmenting cervical cell images in medical diagnostics.

Objective

This study explores the application of deep learning techniques in cervical cell image segmentation, focusing on convolutional neural networks (CNNs), fully convolutional networks, non-coding RNAs and U-Net models. It aims to compare their characteristics, strengths, and weaknesses in enhancing segmentation precision.

Methods

The article surveys recent advancements in deep learning-based cervical cell image segmentation, drawing insights from English literature. It highlights how CNN architectures excel in feature extraction and precise image segmentation, particularly in the context of cervical cells.

Results

Deep learning methodologies, particularly CNN-based models, have significantly improved the accuracy and efficiency of cervical cell image segmentation. Researchers have increasingly adopted these techniques to refine diagnostic capabilities.

Conclusion

The evolving landscape of cervical cell image segmentation, propelled by deep learning advancements, promises enhanced precision and efficiency in clinical diagnostics and treatment support. Future research should continue exploring these technologies to further improve medical outcomes.
宫颈癌仍然是世界范围内一个重要的健康问题,需要有效的诊断方法,如宫颈细胞图像分割。这篇综述概述了在医学诊断中准确分割宫颈细胞图像的挑战和重要性。目的探讨深度学习技术在宫颈细胞图像分割中的应用,重点研究卷积神经网络(cnn)、全卷积网络、非编码rna和U-Net模型。目的是比较它们在提高分割精度方面的特点、优缺点。方法综述了近年来基于深度学习的宫颈细胞图像分割的研究进展,并借鉴了英语文献中的见解。它突出了CNN架构在特征提取和精确图像分割方面的优势,特别是在宫颈细胞的背景下。结果深度学习方法,特别是基于cnn的模型,显著提高了宫颈细胞图像分割的准确性和效率。研究人员越来越多地采用这些技术来改进诊断能力。结论在深度学习的推动下,宫颈细胞图像分割的发展前景有望提高临床诊断和治疗支持的准确性和效率。未来的研究应继续探索这些技术,以进一步改善医疗结果。
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引用次数: 0
Illustration of the variable 1D sequences but conserved 2D and 3D structures of different ncRNA nanostructures for tracking the evolution and origin of organisms 用于跟踪生物体进化和起源的不同ncRNA纳米结构的可变1D序列但保守的2D和3D结构的说明
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-30 DOI: 10.1016/j.ncrna.2025.09.003
Kai Jin , Margaret Bohmer , Peixuan Guo
Viruses and other microorganisms are constantly mutating and emerging in different regions. Here, we apply nanotechnology to examine the primary, secondary, and tertiary structures of novel noncoding RNA nanoparticles and find that primary sequences (1D) vary widely between viruses, while secondary (2D) and tertiary structures (3D) are highly conserved. The uniqueness of the phi29 system makes this reported study possible. RNA evolution studies are relevant to the concept of RNA as the origin of life. The recent discovery that RNA is a motile and recombinant entity supports the hypothesis that RNA is the substance of life. Previously, we reported noncoding RNA nanoparticles packaging RNA (pRNA) of the Bacillus virus phi29 (Nature Nanotechnology, 2011, PMID: 21909084; Nature Nanotechnology, 2010, PMID: 21102465; Science, 1987, PMID: 3107124). Phi29 can infect spore-forming Bacillus subtilis, which has long been hidden in the soil with slow or no evolution due to the protection of spores. They are living fossils. The pRNA of the phi29 DNA packaging motor drives the viral motor for DNA transport. In this study, we used existing datasets to search for more pRNAs. Their primary sequence diversity makes it challenging to identify them from the whole genomes of other species. Using the top-down (1D) approach and the bottom-up assembly (3D) approaches, we found that their 2D and 3D structures are highly conserved. Structural conservation enabled us to apply the two-dimensional structure-based approach to find these ncRNAs from databases and identify 12 new pRNAs. The presence of two additional components in the genome, a motor channel protein and a motor ATPase, further confirmed the authenticity of these pRNAs and supported the conclusion that these pRNAs are motor-driven components. Highly conserved and paired left and right loops for assembling the pRNA hexamer were identified in all 12 pRNAs. Artificial modification of the pairing and determination of the virion production activity of the mutated phi29 pRNA further confirmed the conclusion that the secondary and tertiary structures are highly conserved. Understanding the retention, conservation, and variation of viral non-coding RNA sequences and structure can help us trace the evolutionary history of the virus, find lineage information, and provide important information about the origin of the viruses. It can also provide knowledge for the design of disease prevention and treatment by providing the background for in vivo RNA nanotechnology.
病毒和其他微生物在不同地区不断变异和出现。在这里,我们应用纳米技术研究了新型非编码RNA纳米颗粒的一级、二级和三级结构,发现一级序列(1D)在病毒之间差异很大,而二级(2D)和三级结构(3D)高度保守。phi29系统的独特性使得这项研究成为可能。RNA进化研究与RNA是生命起源的概念有关。最近发现RNA是一种可运动和重组的实体,这支持了RNA是生命物质的假设。此前,我们报道了芽孢杆菌病毒phi29的非编码RNA纳米颗粒包装RNA (pRNA) (Nature Nanotechnology, 2011, PMID: 21909084; Nature Nanotechnology, 2010, PMID: 21102465; Science, 1987, PMID: 3107124)。Phi29可以感染形成孢子的枯草芽孢杆菌,由于孢子的保护,枯草芽孢杆菌长期隐藏在土壤中,进化缓慢或没有进化。他们是活化石。phi29 DNA包装马达的pRNA驱动病毒马达进行DNA运输。在这项研究中,我们使用现有的数据集来搜索更多的prna。它们的初级序列多样性使得从其他物种的整个基因组中识别它们具有挑战性。采用自顶向下(1D)和自底向上组装(3D)方法,我们发现它们的二维和三维结构高度保守。结构守恒使我们能够应用基于二维结构的方法从数据库中找到这些ncrna,并鉴定出12个新的prna。基因组中存在另外两个成分,一个运动通道蛋白和一个运动atp酶,进一步证实了这些prna的真实性,并支持这些prna是运动驱动成分的结论。在所有12种pRNA中均鉴定出高度保守且成对的左右环,用于组装pRNA六聚体。人工修饰配对和测定突变phi29 pRNA的病毒粒子产生活性进一步证实了其二级和三级结构高度保守的结论。了解病毒非编码RNA序列和结构的保留、保存和变异可以帮助我们追踪病毒的进化史,找到谱系信息,并提供有关病毒起源的重要信息。它还可以通过为体内RNA纳米技术提供背景,为疾病预防和治疗的设计提供知识。
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引用次数: 0
ncFN: a comprehensive non-coding RNA function annotation framework based on a global and heterogeneous biomolecular network ncFN:基于全球异质生物分子网络的综合性非编码RNA功能注释框架
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.ncrna.2025.09.007
Min Long , Haizhou Liu , Mengqin Yuan , Xu Zhou , Tao Zhang , Quan Wang , Wei Jiang
Increasing evidence indicates that non-coding RNAs (ncRNAs) have emerged as essential factors in most biological processes through diverse mechanisms. However, the biological functions of most ncRNAs are still poorly understood. Here, we developed ncFN, a novel and comprehensive framework for ncRNA function annotation based on a global and heterogeneous biomolecular network. Specifically, we constructed a Global Interaction Network (GIN) by integrating ncRNA-ncRNA, ncRNA-protein coding gene (PCG), and PCG-PCG interactions. The GIN consists of 565,482 edges connecting 17,060 PCGs and 12,616 ncRNAs, including 1095 microRNAs (miRNAs), 3563 long non-coding RNAs (lncRNAs), and 7958 circular RNAs (circRNAs). For each ncRNA, we quantified Association Strengths (ASs) between the ncRNA and PCGs through Random Walk with Restart in GIN. Then, Gene Set Enrichment Analysis was performed with ASs as input to annotate the function of the ncRNA. Compared to most conventional methods that only focus on a single ncRNA type, ncFN offers significant advantages in covering diverse ncRNA types and a larger number of ncRNA molecules. Moreover, we demonstrated the superiority of ncFN by comparing it with other methods in the annotation of well-acknowledged disease-relevant ncRNAs and differentially expressed ncRNAs in diseases. Finally, ncFN also facilitated enrichment analysis with multiple ncRNAs or pathways as input. In conclusion, ncFN is a comprehensive and reliable tool for functional annotation of miRNAs, lncRNAs, and circRNAs, making it highly suitable for widespread use in ncRNA research. ncFN is freely accessible at http://www.jianglab.cn/ncFN/, and all codes are deposited on GitHub (https://github.com/LongMin0705/ncFN).
越来越多的证据表明,非编码rna (ncRNAs)已通过多种机制成为大多数生物过程的重要因素。然而,大多数ncrna的生物学功能仍然知之甚少。在这里,我们开发了ncFN,一个基于全球异质生物分子网络的ncRNA功能注释的新颖而全面的框架。具体来说,我们通过整合ncRNA-ncRNA、ncrna -蛋白编码基因(PCG)和PCG-PCG相互作用构建了一个全局相互作用网络(GIN)。GIN由565,482条边组成,连接17,060个pcg和12,616个ncrna,包括1095个microrna (mirna), 3563个长非编码rna (lncrna)和7958个环状rna (circrna)。对于每个ncRNA,我们通过GIN中的随机行走与重启来量化ncRNA与pcg之间的关联强度(ASs)。然后,以as为输入进行基因集富集分析,以注释ncRNA的功能。与大多数仅关注单一ncRNA类型的传统方法相比,ncFN在覆盖多种ncRNA类型和大量ncRNA分子方面具有显着优势。此外,我们通过比较ncFN与其他方法在标注公认的疾病相关ncrna和疾病中差异表达的ncrna方面的优势,证明了ncFN的优越性。最后,ncFN还促进了以多个ncrna或通路作为输入的富集分析。综上所述,ncFN是一种全面可靠的mirna、lncrna和circrna功能标注工具,非常适合广泛应用于ncRNA研究。ncFN可以免费访问http://www.jianglab.cn/ncFN/,所有代码都存放在GitHub (https://github.com/LongMin0705/ncFN)上。
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引用次数: 0
LncRNA-EME1 enhances BRCA1 recruitment and alters repair of DNA damage in cervical cancer radioresistance LncRNA-EME1增强BRCA1募集并改变宫颈癌放射抵抗中DNA损伤的修复
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-19 DOI: 10.1016/j.ncrna.2025.09.006
Qing Li, Zhenyu Zhou, Xiaoying Li, Qiongyu Lan

Background

Cervical cancer is a significant cause of mortality in women globally, and radioresistance limits the effectiveness of standard radiotherapy treatment. Exploring the molecular mechanisms that contribute to radioresistance is vital for improving therapies. This study focuses on the role of lncRNA in influencing the radioresistance of cervical cancer.

Methods

We identified lncRNA-EME1 as a candidate regulator of cervical cancer radioresistance through transcriptomic sequencing and RT-qPCR. Its function was explored by silencing or overexpressing lncRNA-EME1, followed by proliferation (MTT), clonogenic survival, apoptosis, and ROS assays. Effects on BRCA1 expression and DNA damage response were examined by WB, γ-H2AX focus analysis, and the I-SceI-mediated homologous recombination assay. Mechanistic insights were obtained using RNA pull-down and RIP assays. Finally, a xenograft model with subsequent TUNEL and immunohistochemical analyses was used to validate the role of lncRNA-EME1 in regulating BRCA1 and mediating radioresistance in vivo.

Results

Our findings indicate that lncRNA-EME1 is overexpressed in radioresistant cervical cancer cells. Silencing lncRNA-EME1 enhances radiosensitivity in HeLa-IR and SiHa-IR cells, suppresses malignant phenotypes, and increases apoptosis and ROS levels. This effects corresponds with reduced BRCA1 expression and alterations in DNA damage repair markers, highlighting its role in the radiation response. The positive association between lncRNA-EME1 and BRCA1 further supports its involvement in DNA damage repair, thereby regulating cervical cancer cells' sensitivity to radiation therapy. In vivo xenograft experiments further confirmed that lncRNA-EME1 promotes BRCA1 expression and contributes to cervical cancer radioresistance.

Conclusion

This study sheds light on the role of lncRNA-EME1 in regulating BRCA1 activity and contributing to cervical cancer radioresistance. Our data reveals that decreasing lncRNA-EME1 expression could potentially boost radiosensitivity in cervical cancer cells.
宫颈癌是全球妇女死亡的重要原因之一,放射耐药限制了标准放射治疗的有效性。探索导致放射耐药的分子机制对改善治疗至关重要。本研究的重点是lncRNA在影响宫颈癌放射耐药中的作用。方法通过转录组测序和RT-qPCR鉴定lncRNA-EME1是宫颈癌放射耐药的候选调控因子。通过沉默或过表达lncRNA-EME1,随后进行增殖(MTT)、克隆存活、细胞凋亡和ROS检测来探索其功能。通过WB、γ-H2AX聚焦分析和i - scei介导的同源重组实验检测BRCA1表达和DNA损伤反应的影响。通过RNA下拉和RIP测定获得机制见解。最后,采用异种移植物模型进行TUNEL和免疫组织化学分析,验证lncRNA-EME1在体内调节BRCA1和介导放射耐药中的作用。结果lncRNA-EME1在宫颈癌放射耐药细胞中过表达。沉默lncRNA-EME1可增强HeLa-IR和SiHa-IR细胞的放射敏感性,抑制恶性表型,增加细胞凋亡和ROS水平。这种影响与BRCA1表达减少和DNA损伤修复标记的改变相对应,突出了其在辐射反应中的作用。lncRNA-EME1与BRCA1之间的正相关进一步支持其参与DNA损伤修复,从而调节宫颈癌细胞对放射治疗的敏感性。体内异种移植实验进一步证实,lncRNA-EME1促进BRCA1表达,参与宫颈癌放射耐药。结论本研究揭示了lncRNA-EME1在调控BRCA1活性和促进宫颈癌放射耐药中的作用。我们的数据显示,lncRNA-EME1表达的降低可能会潜在地提高宫颈癌细胞的放射敏感性。
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引用次数: 0
Long non-coding RNAs in B-cell acute lymphoblastic leukemia: Disease implication, challenges and therapeutic opportunities b细胞急性淋巴细胞白血病中的长链非编码rna:疾病含义、挑战和治疗机会
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-16 DOI: 10.1016/j.ncrna.2025.09.005
Devesh Srivastava, Ashish Misra
B-cell acute lymphoblastic leukemia (B-ALL) manifests as an abnormal proliferation of neoplastic B-cell lymphocytes, adversely affecting both children and adults. Despite the advancements in cancer research, B-ALL cure remains challenging due to the complexity of the disease and immense subtype heterogeneity. Better understanding of the molecular mechanisms driving B-ALL pathogenesis is imperative to identify the novel therapeutic markers that can impede disease progression. Genomic and transcriptomic studies involving patient samples have underscored the emerging role of long non-coding RNAs (lncRNAs) in the diverse B-ALL landscape. Their dysregulation has been linked to malignant proliferation, metastasis, and varying patient survival outcomes. Gaining detailed mechanistic insights into the role of lncRNAs in B-ALL pathophysiology is pivotal for understanding their contributions to disease progression and developing new therapeutics. Herein, we have comprehensively discussed B-ALL and its diverse subtypes, focusing on the pivotal role played by various lncRNAs in fine-tuning signaling pathways, disease heterogeneity and progression. We have also explored recent advances in our understanding of the diverse classes of lncRNA inhibitors, evaluating their potential as B-ALL therapeutics and challenges associated with their development.
b细胞急性淋巴细胞白血病(B-ALL)表现为肿瘤b细胞淋巴细胞的异常增殖,对儿童和成人都有不良影响。尽管癌症研究取得了进步,但由于疾病的复杂性和巨大的亚型异质性,B-ALL的治愈仍然具有挑战性。更好地了解驱动B-ALL发病机制的分子机制对于确定能够阻止疾病进展的新型治疗标记物至关重要。涉及患者样本的基因组和转录组学研究强调了长链非编码rna (lncrna)在不同B-ALL环境中的新兴作用。它们的失调与恶性增殖、转移和不同的患者生存结果有关。深入了解lncrna在B-ALL病理生理中的作用机制,对于理解它们对疾病进展的贡献和开发新的治疗方法至关重要。在此,我们全面讨论了B-ALL及其不同亚型,重点讨论了各种lncrna在微调信号通路、疾病异质性和进展中发挥的关键作用。我们还探索了我们对不同种类lncRNA抑制剂的理解的最新进展,评估了它们作为B-ALL治疗药物的潜力以及与它们的发展相关的挑战。
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引用次数: 0
AQUARIUM_HB: a bioinformatics pipeline for human blood circular RNA analysis AQUARIUM_HB:用于人血液环状RNA分析的生物信息学管道
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-15 DOI: 10.1016/j.ncrna.2025.09.004
Shaoxun Yuan , Xue Bai , Linwei Li , Wanjun Gu
Accurately identifying and quantifying human blood circular RNAs (circRNAs) from RNA-seq data is a critical bioinformatics challenge in biomarker discovery for human diseases. In this study, we present AQUARIUM-HB, a comprehensive bioinformatics pipeline for identifying, quantifying, annotating, and analyzing circRNAs from human blood transcriptomes. AQUARIUM-HB includes three functional modules. First, it identifies and annotates circRNAs from rRNA-depleted RNA-seq datasets of human blood samples. Second, it performs an in-depth expression analysis of blood circRNAs. Third, it constructs a reference set of full-length blood circRNAs. We demonstrate the application of AQUARIUM-HB using a human blood RNA-seq dataset from COVID-19 patients, showcasing its potential for improving the accuracy and depth of circRNA biomarker discovery.
从RNA-seq数据中准确鉴定和定量人类血液环状rna (circRNAs)是发现人类疾病生物标志物的关键生物信息学挑战。在这项研究中,我们提出了水族馆- hb,一个全面的生物信息学管道,用于鉴定、定量、注释和分析来自人类血液转录组的环状rna。水族馆hb包括三个功能模块。首先,它从人类血液样本的rrna耗尽的RNA-seq数据集中识别和注释环状rna。其次,对血液环状rna进行深入的表达分析。第三,构建全长血环rna参考集。我们使用来自COVID-19患者的人类血液RNA-seq数据集展示了AQUARIUM-HB的应用,展示了其在提高circRNA生物标志物发现的准确性和深度方面的潜力。
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引用次数: 0
miRNA-195-5p modulates cell proliferation and stemness by targeting the Wnt signalling network in breast cancer miRNA-195-5p通过靶向Wnt信号网络调节乳腺癌细胞增殖和干细胞性
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-13 DOI: 10.1016/j.ncrna.2025.09.001
Sanjeev Kumar , Neeru Saini
Cancer stem cells (CSCs) are a specific subpopulation of cells within the tumour characterised by self-renewal, proliferation and tumorigenic potential. Heterogeneity in the CSCs population and their ability to rewire the signalling networks make it difficult to target cancer by single gene inhibition. This study investigates the regulatory role of miR-195-5p in modulating CSC properties and associated signalling pathways in breast cancer. Previously shown to inhibit proliferation, invasion, and metastasis, miR-195-5p is now revealed to downregulate stemness markers (OCT4, SOX2, NANOG, and CD44). The prevalence of heterogeneity of stemness markers in MCF-7 and MDA-MB-231 cell lines is a novel advancement of this study. In MCF-7, SOX2-and CD44-overexpressing cells were found to be distinct, non-overlapping populations, as confirmed by immunofluorescence colocalisation analysis. SOX2-positive nuclei comprised ∼30 % of the MCF-7 population and were significantly reduced following miR-195-5p overexpression. Mechanistically, this downregulation of stemness correlated with decreased expression of β-catenin and its upstream regulators GSK3β and FZD6, were validated as direct targets of miR-195-5p using a luciferase reporter assay. miR-195-5p also inhibited TCF/LEF transcriptional activity, indicating suppression of canonical Wnt/β-catenin signalling. Functionally, miR-195-5p overexpression led to a reduced proliferation zone in CFSE-prestained 3D spheres derived from MCF-7 cells over seven days. To further dissect its mechanism, Wnt signalling was perturbed using siRNA against GSK3β, β-catenin and ICG-001 (a CBP/β-catenin interaction inhibitor), and their combination. GSK3β knockdown led to increased β-catenin expression, nuclear localisation, and enhanced 3D sphere proliferation, while β-catenin inhibition upregulated protein expression of GSK3β and suppressed proliferation of cancer cells. Combined inhibition of GSK3β and CBP/β-catenin interaction downregulated expression of β-catenin, supporting the role of miR-195-5p in CSC suppression. This study identifies miR-195-5p as a potent regulator of CSCs and proliferation, and modulator of the Wnt signalling cascade. Co-inhibition of GSK3β and CBP/β-catenin through miR-195-5p highlights its therapeutic potential in combating stemness and proliferation in breast cancer.
肿瘤干细胞(CSCs)是肿瘤内具有自我更新、增殖和致瘤潜能的特定细胞亚群。CSCs群体的异质性及其重新连接信号网络的能力使其难以通过单基因抑制靶向癌症。本研究探讨了miR-195-5p在乳腺癌中调节CSC特性和相关信号通路中的调节作用。先前显示miR-195-5p抑制增殖、侵袭和转移,现在发现miR-195-5p下调干性标记(OCT4、SOX2、NANOG和CD44)。干细胞标记在MCF-7和MDA-MB-231细胞系中异质性的普遍存在是本研究的一个新进展。免疫荧光共定位分析证实,在MCF-7中,sox2和cd44过表达细胞是不同的、不重叠的群体。sox2阳性细胞核占MCF-7群体的30%,并且在miR-195-5p过表达后显著减少。在机制上,这种干性下调与β-catenin及其上游调节因子GSK3β和FZD6的表达降低相关,通过荧光素酶报告基因试验证实了它们是miR-195-5p的直接靶点。miR-195-5p还抑制了TCF/LEF的转录活性,表明抑制了典型的Wnt/β-catenin信号传导。在功能上,miR-195-5p过表达导致MCF-7细胞衍生的cfse染色3D球在7天内增殖区减少。为了进一步分析其机制,使用siRNA干扰GSK3β、β-catenin和ICG-001(一种CBP/β-catenin相互作用抑制剂)及其组合,干扰Wnt信号。GSK3β敲低导致β-catenin表达增加,核定位增加,3D球增殖增强,而β-catenin抑制上调GSK3β蛋白表达,抑制癌细胞增殖。联合抑制GSK3β和CBP/β-catenin相互作用下调β-catenin的表达,支持miR-195-5p在CSC抑制中的作用。本研究确定miR-195-5p是CSCs和增殖的有效调节剂,也是Wnt信号级联的调节剂。通过miR-195-5p共同抑制GSK3β和CBP/β-catenin,突出了其在对抗乳腺癌干细胞和增殖方面的治疗潜力。
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引用次数: 0
Circadian rhythm-related miR-6883-5p suppresses enzalutamide-resistant prostate cancer 与昼夜节律相关的miR-6883-5p抑制恩杂鲁胺耐药前列腺癌
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-12 DOI: 10.1016/j.ncrna.2025.09.002
Wenchang Yue , Chao Li , Tao Wang , Jiawei You , Jiale Sun , Jiapeng Liu , Ashutosh K. Tewari , Kyprianou Natasha , Mariana G. Figueiro , Jianquan Hou , Babu J. Padanilam
The increasing incidence of prostate cancer (PCa), particularly the emergence of treatment-resistant castration-resistant prostate cancer (CRPC), has intensified research efforts to address this lethal disease. Circadian rhythm gene alterations have been identified as critical factors influencing PCa progression and treatment resistance, warranting further investigation into their roles in PCa biology.
In this study, we identified a significant downregulation of PER1 and its associated miRNA, miR-6883-5p, in PCa cells and clinical samples, suggesting their potential clinical relevance. Functional analyses demonstrated that miR-6883-5p suppresses the proliferation of enzalutamide-resistant PCa cells both in vitro and in vivo by directly targeting AR-V7. Furthermore, we delineated the regulatory functions of the transcription factors BMAL1 and CLOCK in promoting the expression of PER1 and miR-6883-5p, while miR-6883-5p negatively regulates CLOCK expression, thereby impacting the transcription-translation feedback loop (TTFL) of circadian genes.
Collectively, these findings uncover a regulatory axis involving circadian rhythm components, miR-6883-5p, AR-V7, and PCa progression, providing new mechanistic insights into treatment resistance in CRPC and highlighting the circadian clock as a potential therapeutic target.
前列腺癌(PCa)发病率的增加,特别是治疗抵抗性去势抵抗性前列腺癌(CRPC)的出现,加强了对这一致命疾病的研究努力。昼夜节律基因改变已被确定为影响前列腺癌进展和治疗耐药性的关键因素,需要进一步研究其在前列腺癌生物学中的作用。在这项研究中,我们在PCa细胞和临床样本中发现了PER1及其相关miRNA miR-6883-5p的显著下调,这表明它们可能具有临床相关性。功能分析表明,miR-6883-5p通过直接靶向AR-V7,在体外和体内抑制enzalutamide耐药PCa细胞的增殖。此外,我们描述了转录因子BMAL1和CLOCK在促进PER1和miR-6883-5p表达方面的调节功能,而miR-6883-5p负调控CLOCK表达,从而影响昼夜节律基因的转录-翻译反馈回路(TTFL)。总的来说,这些发现揭示了一个涉及昼夜节律成分、miR-6883-5p、AR-V7和PCa进展的调控轴,为CRPC治疗耐药提供了新的机制见解,并突出了生物钟作为潜在的治疗靶点。
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引用次数: 0
Non-coding RNAs in congenital heart disease and placental development: Bridging molecular mechanisms to clinical biomarkers and therapies 先天性心脏病和胎盘发育中的非编码rna:连接临床生物标志物和治疗的分子机制
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-01 DOI: 10.1016/j.ncrna.2025.08.006
Haoxuan Wang , Xinzhe Chen , Yinghui Li , Shudan Xiao , Tianqi Teng , Sumin Yang , Kun Wang , Meihua Zhang
Non-coding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, orchestrating embryonic development and disease pathogenesis. This review synthesizes current knowledge on the origin, biogenesis, and functional diversity of ncRNAs, with a focus on their regulatory crosstalk in congenital heart disease (CHD) and placental development. The fetal heart-placenta axis, a bidirectional signaling network essential for cardiogenesis and placental morphogenesis, is spatiotemporally modulated by ncRNAs through epigenetic and post-transcriptional mechanisms. Through precise regulation of cardiac cell differentiation, angiogenesis, and trophoblast invasion, ncRNAs maintain developmental homeostasis, whereas their dysregulation disrupts these processes, contributing to CHD pathogenesis and positioning them as promising biomarkers. Collectively, this review establishes ncRNAs as molecular bridges between the fetal heart-placenta axis and clinical translation, underscoring their dual utility as diagnostic biomarkers for CHD and modifiable targets to correct placental maldevelopment, thereby advancing precision therapies for congenital disorders.
非编码rna (ncRNAs)已成为基因表达的关键调控因子,协调胚胎发育和疾病发病机制。本文综述了目前关于ncrna的起源、生物发生和功能多样性的知识,重点介绍了它们在先天性心脏病(CHD)和胎盘发育中的调控串扰。胎儿心脏-胎盘轴是一个对心脏发生和胎盘形态发生至关重要的双向信号网络,ncrna通过表观遗传和转录后机制对其进行时空调节。通过对心脏细胞分化、血管生成和滋养细胞侵袭的精确调控,ncrna维持了发育稳态,而它们的失调破坏了这些过程,促进了冠心病的发病机制,并将它们定位为有前途的生物标志物。总的来说,本综述确立了ncrna作为胎儿心脏-胎盘轴和临床翻译之间的分子桥梁,强调了它们作为冠心病诊断生物标志物和纠正胎盘发育不良的可修饰靶点的双重用途,从而推进先天性疾病的精确治疗。
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引用次数: 0
Exosome-like nanovesicles from Dunaliella salina efficient sequential Co-delivery of anti-PDL1 and miR-375 for enhancing gene/immune therapy 来自盐杜氏藻的外泌体样纳米囊泡有效地先后递送抗pdl1和miR-375以增强基因/免疫治疗
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-09-01 DOI: 10.1016/j.ncrna.2025.08.007
Zhaoyi Wei , Mengxi Zhu , Shan Li , Junling An , Yiwen Liu , Shuying Feng , Tingting Yang , Shegan Gao , Gaofeng Liang

Background

Esophageal cancer is one of the common malignant tumors of digestive system. Despite many advances in the treatment of esophageal cancer, many challenges remain. As an endogenous extracellular vesicle, exosomes are increasingly presenting their immense potential in drug delivery. However, it remains a bottleneck to obtain a large quantity of uniform, stable, and multi-component controllable exosomes with low cost and time.

Methods

A novel targeted drug delivery system based on exosome-like nanovesicles has been developed using the natural Marine single-celled salt Dunaliella salina (DENV) to conjugate c (RGDyK) peptide on its surface to achieve targeted drug delivery to esophageal cancer cells. In addition, miR-375 was loaded into cRGD-DENV by electroporation and aPD-L1 was coupled to its surface by matrix metalloproteinase-2 (MMP-2). Characterizations were performed to confirm the successful preparation of engineered exosomes. The effects of engineered exosomes on tumor cell viability, migration, invasion and apoptosis were examined in vitro and the effects of engineered exosomes on esophageal cancer cells were further verified in vivo.

Results

The engineered DENV delivery system was prepared and characterized. It exhibited a uniform particle diameter (approximately 150 nm) with in vitro sustained release features in the presence of MMP-2/9. Importantly, the cRGD-DENV was effective, promoted selective delivery of cargoes to the tumor site, and reduced nonspecific uptake of the DENV cargoes, significantly inhibiting tumor growth in vitro. In vivo results showed that cRGD-DENV-aPDL1/miR375 significantly inhibited tumor growth and affected the proliferation, migration and invasion of esophageal cancer cells by regulating YWHAZ.

Conclusions

The potential of Dunaliella salina exosome-like nanovesicle carrier delivery system in cancer therapy and can provide a very promising platform for the rapid and large-scale generation of functionalized exosome-like nanovesicles.
食管癌是消化系统常见的恶性肿瘤之一。尽管食管癌的治疗取得了许多进展,但仍存在许多挑战。外泌体作为一种内源性细胞外囊泡,在药物传递方面越来越显示出巨大的潜力。然而,如何以较低的成本和时间获得大量均匀、稳定、多组分可控的外泌体仍然是一个瓶颈。方法利用天然海洋单细胞盐Dunaliella salina (DENV)在其表面偶联c (RGDyK)肽,构建一种基于外泌体样纳米囊泡的靶向给药系统,实现对食管癌细胞的靶向给药。此外,通过电穿孔将miR-375加载到cRGD-DENV中,并通过基质金属蛋白酶-2 (MMP-2)将aPD-L1偶联到其表面。进行表征以确认工程外泌体的成功制备。在体外研究了工程外泌体对肿瘤细胞活力、迁移、侵袭和凋亡的影响,并在体内进一步验证了工程外泌体对食管癌细胞的作用。结果制备了工程化的DENV输送系统,并对其进行了表征。其颗粒直径均匀(约150 nm),在MMP-2/9存在下具有体外缓释特性。重要的是,cRGD-DENV是有效的,促进了肿瘤部位的选择性递送,减少了DENV货物的非特异性摄取,在体外显著抑制肿瘤生长。体内实验结果显示,cRGD-DENV-aPDL1/miR375通过调控YWHAZ显著抑制肿瘤生长,影响食管癌细胞的增殖、迁移和侵袭。结论盐杜氏藻外泌体样纳米囊泡载体系统在肿瘤治疗中的应用潜力巨大,为快速、大规模制备功能化外泌体样纳米囊泡提供了良好的平台。
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Non-coding RNA Research
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