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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 : 2026-02-01 Epub 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
Keratinocyte-specific long non-coding RNA NR037661 controls alternative splicing of ANGPTL4 to induce keratinocyte differentiation 角化细胞特异性长链非编码RNA NR037661控制ANGPTL4的选择性剪接以诱导角化细胞分化
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-10-14 DOI: 10.1016/j.ncrna.2025.10.003
Chunxiao Li , Qinyuan Zhu , Xinhang Cao , Dandan Xiao , Hui Yang , Xiang Kong , Ziyu Wang , Mingzhe Ma , Yangbai Sun

Background

Aberrant differentiation of keratinocytes has been implicated in various skin diseases. However, the impact of lncRNA on keratinocyte differentiation and RNA alternative splicing remains poorly understood. The primary aim of this study was to delineate the landscape of differentially expressed lncRNAs in keratinocytes undergoing differentiation and to elucidate the underlying molecular mechanisms.

Methods

Primary human keratinocytes (HKEn) were subjected to comprehensive microarray analysis to identify the differentially expressed lncRNAs upon calcium stimulation. Loss-of-function experiments were carried out to explore the role of NR037661 in keratinocyte differentiation. RNA sequencing analysis was performed to study the potential target genes of NR037761. RNA pull-down assay, SDS-PAGE, silver staining and mass spectrometry analysis were utilized to explore the potential proteins that interacted with NR037761 and participated in NR037761-mediated keratinocyte differentiation. The effects of NR037761 on the alternative splicing and expression of Angiopoietin-like 4 (ANGPTL4) were analyzed by RT-PCR and Western blot.

Results

NR037661 specifically interacts with the splicing factor Serine/arginine repetitive matrix protein 2 (SRRM2), facilitating its nuclear localization. This interaction modulates the alternative splicing (AS) of ANGPTL4 mRNA, ultimately influencing keratinocyte differentiation.

Conclusions

Our findings illuminate a novel regulatory mechanism underlying keratinocyte differentiation, potentially revealing new therapeutic targets for skin diseases.
背景:角质形成细胞的异常分化与多种皮肤病有关。然而,lncRNA对角质细胞分化和RNA选择性剪接的影响仍然知之甚少。本研究的主要目的是描述角化细胞分化过程中lncrna差异表达的情况,并阐明其潜在的分子机制。方法对人原代角质形成细胞(HKEn)进行微阵列分析,鉴定钙刺激下差异表达的lncrna。通过功能缺失实验探讨NR037661在角质形成细胞分化中的作用。通过RNA测序分析研究NR037761的潜在靶基因。利用RNA下拉法、SDS-PAGE、银染色和质谱分析探索与NR037761相互作用并参与NR037761介导的角质细胞分化的潜在蛋白。采用RT-PCR和Western blot分析NR037761对ANGPTL4 (Angiopoietin-like 4)选择性剪接和表达的影响。结果snr037661与剪接因子丝氨酸/精氨酸重复基质蛋白2 (SRRM2)特异性相互作用,促进其核定位。这种相互作用调节ANGPTL4 mRNA的选择性剪接(AS),最终影响角质形成细胞的分化。结论sour的发现揭示了角质细胞分化的新调控机制,可能为皮肤病的治疗提供新的靶点。
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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 : 2026-02-01 Epub 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
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 : 2026-02-01 Epub 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
List of reviewers in 2025 2025年审稿人名单
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-22 DOI: 10.1016/j.ncrna.2026.01.005
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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 : 2026-02-01 Epub 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
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 : 2026-02-01 Epub 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
Integrative analysis of tissue and circulating miRNAs as biomarkers for progression and survival in hepatocellular carcinoma 组织和循环mirna作为肝细胞癌进展和生存的生物标志物的综合分析
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-25 DOI: 10.1016/j.ncrna.2025.11.002
Abdullah Jabri , Abdulaziz Mhannayeh , Mohamed Alsharif , Bader Taftafa , Tooba Mujtaba , Arshiya Akbar , Ahmed Abu-zaid , Tanveer Ahmad Mir , Mohammad Imran Khan , Firoz Ahmed , Itika Arora , Ahmed Yaqinuddin
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with limited biomarkers available for early diagnosis and risk stratification. In this study, we performed an integrative analysis of tissue and circulating microRNA (miRNA) expression profiles to identify candidates linked to disease progression and clinical outcomes. Tumor miRNA data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) and serum miRNA data from the Gene Expression Omnibus (GSE113740) were analyzed using differential expression, survival analysis, functional enrichment, and clinical subgroup evaluation. We identified 16 significantly dysregulated miRNAs in HCC tissues, including hsa-miR-187 and hsa-miR-6718, which were associated with poor survival, and hsa-miR-5589, which showed a protective effect. Clinical analyses revealed stage-specific upregulation of hsa-miR-106b and downregulation of the hsa-miR-124 family in metastatic tumors. Functional enrichment highlighted pathways such as PI3K-Akt, MAPK signalling, and nucleocytoplasmic transport. Circulating miRNAs, including hsa-miR-3619-3p, hsa-miR-1290, and hsa-miR-1185-2-3p, correlated with AFP levels and disease stage, underscoring their value as non-invasive biomarkers. These findings demonstrate that integrated analysis of tissue and serum miRNAs can identify clinically relevant biomarkers and potential therapeutic targets in HCC.
肝细胞癌(HCC)是癌症相关死亡的主要原因,可用于早期诊断和风险分层的生物标志物有限。在这项研究中,我们对组织和循环microRNA (miRNA)表达谱进行了综合分析,以确定与疾病进展和临床结果相关的候选物。来自肝癌基因组图谱(TCGA-LIHC)的肿瘤miRNA数据和来自基因表达图谱(GSE113740)的血清miRNA数据通过差异表达、生存分析、功能富集和临床亚组评估进行分析。我们在HCC组织中发现了16个显著失调的mirna,包括与生存差相关的hsa-miR-187和hsa-miR-6718,以及具有保护作用的hsa-miR-5589。临床分析显示,转移性肿瘤中hsa-miR-106b的分期特异性上调和hsa-miR-124家族的下调。功能富集强调了PI3K-Akt、MAPK信号传导和核质转运等途径。循环mirna,包括hsa-miR-3619-3p、hsa-miR-1290和hsa-miR-1185-2-3p,与AFP水平和疾病分期相关,强调了它们作为非侵入性生物标志物的价值。这些发现表明,对组织和血清mirna的综合分析可以识别HCC临床相关的生物标志物和潜在的治疗靶点。
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引用次数: 0
miR-6850 drives phenotypic changes and signaling in high grade serous ovarian cancer miR-6850驱动高级别浆液性卵巢癌的表型变化和信号传导
IF 4.7 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-11-05 DOI: 10.1016/j.ncrna.2025.10.004
Kamil Filipek , Daniela Pollutri , Ivana Kurelac , Giuseppe Gasparre , Marianna Penzo
MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression, and their dysregulation is closely linked to cancer development. Ovarian cancer (OC), particularly the high-grade serous ovarian carcinoma (HGSOC) subtype, is the most lethal gynecological malignancy, primarily due to late-stage diagnosis and limited treatment options. Among the miRNAs encoded at the often amplified 8q24.3 region, miR-6850 has emerged as a potential candidate target owing to its genomic positioning inside this hotspot and its unexpectedly low expression in HGSOC tissues and cell lines. In silico investigations indicated that, despite the gain in MIR6850 copy number, its mature products, miR-6850-5p and miR-6850-3p, were expressed at low levels; notably, MIR6850 gene amplification was associated with enhanced disease-specific survival. Functional studies revealed that ectopic production of both isoforms in SKOV-3 and NIH:OVCAR3 cells inhibited proliferation, compromised clonogenic capacity, and disturbed cell cycle progression. Moreover, miR-6850 altered cell phenotype by facilitating mesenchymal-to-epithelial transition (MET), as shown by the overexpression of E-cadherin and β-catenin and the downregulation of Slug and Vimentin. It also regulated cell adhesion and migration while reducing global protein synthesis via the downregulation of the PI3K/Akt/mTOR pathway. Our results together identify miR-6850 as a tumor-suppressive miRNA in HGSOC, demonstrating its diverse anti-oncogenic actions and underscoring its potential as a prognostic biomarker and therapeutic target in ovarian cancer.
MicroRNAs (miRNAs)是基因表达的关键转录后调控因子,其失调与癌症的发生密切相关。卵巢癌(OC),特别是高级别浆液性卵巢癌(HGSOC)亚型,是最致命的妇科恶性肿瘤,主要是由于晚期诊断和有限的治疗选择。在经常被扩增的8q24. 4.3区域编码的mirna中,miR-6850由于其基因组定位在该热点内,并且在HGSOC组织和细胞系中的表达出乎意料地低,因此已成为潜在的候选靶标。计算机研究表明,尽管MIR6850拷贝数增加,但其成熟产物miR-6850-5p和miR-6850-3p的表达水平较低;值得注意的是,MIR6850基因扩增与疾病特异性生存率的提高相关。功能研究显示,SKOV-3和NIH:OVCAR3细胞中异位异构体的产生抑制了增殖,损害了克隆生成能力,并扰乱了细胞周期进程。此外,miR-6850通过促进间充质向上皮转化(MET)改变细胞表型,如E-cadherin和β-catenin的过表达以及Slug和Vimentin的下调。它还通过下调PI3K/Akt/mTOR通路来调节细胞粘附和迁移,同时减少全局蛋白合成。我们的研究结果共同确定了miR-6850在HGSOC中是一种肿瘤抑制miRNA,展示了其多种抗致癌作用,并强调了其作为卵巢癌预后生物标志物和治疗靶点的潜力。
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引用次数: 0
Overview of small proteins encoded by bacterial dual-function small RNAs 细菌双功能小rna编码小蛋白综述
IF 5.9 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-01 Epub Date: 2025-07-06 DOI: 10.1016/j.ncrna.2025.07.002
Xia Cai , Hui Shan , Jiaojiao Wang , Jiaxin Qin , Huiling Gong , Jun Cai , Jin He
Small RNAs (sRNAs) are widely used by bacteria to regulate diverse biological processes. Although they are generally considered “non-coding”, some sRNAs (called dual-function sRNAs) have been found to encode small proteins, which are usually less than 50 amino acids in length and have long been overlooked due to significant challenges in their annotation and biochemical detection. However, in the past few decades, an increasing number of small proteins encoded by dual-function sRNAs have been reported. Previous reviews of dual-function sRNAs have mainly focused on their base-pairing nucleic acid functions, with less emphasis on the nature of their translated peptides, resulting in limited understanding of their full functional scope. This article reviews ten small proteins encoded by dual-function sRNAs and introduces their physiological functions, interacting protein partners, and the research methods used, aiming to provide new perspectives and directions for the study of small proteins and enhance understanding of bacterial regulatory mechanisms mediated by dual-function sRNAs.
小rna (Small rna, sRNAs)被细菌广泛用于调控多种生物过程。虽然它们通常被认为是“非编码”的,但已经发现一些sRNAs(称为双功能sRNAs)编码小蛋白质,这些小蛋白质通常长度小于50个氨基酸,由于其注释和生化检测方面的重大挑战,长期以来一直被忽视。然而,在过去的几十年里,越来越多的由双功能sRNAs编码的小蛋白被报道出来。以往对双功能sRNAs的综述主要集中在其碱基配对核酸功能上,对其翻译肽的性质关注较少,导致对其全部功能范围的了解有限。本文综述了双功能sRNAs编码的10种小蛋白,并介绍了它们的生理功能、相互作用的蛋白伙伴及其研究方法,旨在为小蛋白的研究提供新的视角和方向,加深对双功能sRNAs介导的细菌调控机制的认识。
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引用次数: 0
期刊
Non-coding RNA Research
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