Pub Date : 2025-09-30DOI: 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.
{"title":"Investigation of cervical cell image segmentation technology based on deep learning and non-coding RNAs","authors":"Cheng Cheng , Yi Yang , Youshan Qu","doi":"10.1016/j.ncrna.2025.09.009","DOIUrl":"10.1016/j.ncrna.2025.09.009","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 54-58"},"PeriodicalIF":4.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-30DOI: 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.
{"title":"Illustration of the variable 1D sequences but conserved 2D and 3D structures of different ncRNA nanostructures for tracking the evolution and origin of organisms","authors":"Kai Jin , Margaret Bohmer , Peixuan Guo","doi":"10.1016/j.ncrna.2025.09.003","DOIUrl":"10.1016/j.ncrna.2025.09.003","url":null,"abstract":"<div><div>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 <em>in vivo</em> RNA nanotechnology.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 156-166"},"PeriodicalIF":4.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-29DOI: 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).
{"title":"ncFN: a comprehensive non-coding RNA function annotation framework based on a global and heterogeneous biomolecular network","authors":"Min Long , Haizhou Liu , Mengqin Yuan , Xu Zhou , Tao Zhang , Quan Wang , Wei Jiang","doi":"10.1016/j.ncrna.2025.09.007","DOIUrl":"10.1016/j.ncrna.2025.09.007","url":null,"abstract":"<div><div>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 <span><span>http://www.jianglab.cn/ncFN/</span><svg><path></path></svg></span>, and all codes are deposited on GitHub (<span><span>https://github.com/LongMin0705/ncFN</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 70-78"},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145326034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-19DOI: 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.
{"title":"LncRNA-EME1 enhances BRCA1 recruitment and alters repair of DNA damage in cervical cancer radioresistance","authors":"Qing Li, Zhenyu Zhou, Xiaoying Li, Qiongyu Lan","doi":"10.1016/j.ncrna.2025.09.006","DOIUrl":"10.1016/j.ncrna.2025.09.006","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>in vivo</em>.</div></div><div><h3>Results</h3><div>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. <em>In vivo</em> xenograft experiments further confirmed that lncRNA-EME1 promotes BRCA1 expression and contributes to cervical cancer radioresistance.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 57-69"},"PeriodicalIF":4.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-16DOI: 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.
{"title":"Long non-coding RNAs in B-cell acute lymphoblastic leukemia: Disease implication, challenges and therapeutic opportunities","authors":"Devesh Srivastava, Ashish Misra","doi":"10.1016/j.ncrna.2025.09.005","DOIUrl":"10.1016/j.ncrna.2025.09.005","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 40-56"},"PeriodicalIF":4.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-15DOI: 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.
{"title":"AQUARIUM_HB: a bioinformatics pipeline for human blood circular RNA analysis","authors":"Shaoxun Yuan , Xue Bai , Linwei Li , Wanjun Gu","doi":"10.1016/j.ncrna.2025.09.004","DOIUrl":"10.1016/j.ncrna.2025.09.004","url":null,"abstract":"<div><div>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 <em>AQUARIUM-HB</em>, a comprehensive bioinformatics pipeline for identifying, quantifying, annotating, and analyzing circRNAs from human blood transcriptomes. <em>AQUARIUM-HB</em> 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 <em>AQUARIUM-HB</em> using a human blood RNA-seq dataset from COVID-19 patients, showcasing its potential for improving the accuracy and depth of circRNA biomarker discovery.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 32-39"},"PeriodicalIF":4.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-13DOI: 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.
{"title":"miRNA-195-5p modulates cell proliferation and stemness by targeting the Wnt signalling network in breast cancer","authors":"Sanjeev Kumar , Neeru Saini","doi":"10.1016/j.ncrna.2025.09.001","DOIUrl":"10.1016/j.ncrna.2025.09.001","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"15 ","pages":"Pages 172-181"},"PeriodicalIF":4.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-12DOI: 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.
{"title":"Circadian rhythm-related miR-6883-5p suppresses enzalutamide-resistant prostate cancer","authors":"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","doi":"10.1016/j.ncrna.2025.09.002","DOIUrl":"10.1016/j.ncrna.2025.09.002","url":null,"abstract":"<div><div>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.</div><div>In this study, we identified a significant downregulation of <em>PER1</em> 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 <em>PER1</em> and miR-6883-5p, while miR-6883-5p negatively regulates CLOCK expression, thereby impacting the transcription-translation feedback loop (TTFL) of circadian genes.</div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 21-31"},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 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.
{"title":"Non-coding RNAs in congenital heart disease and placental development: Bridging molecular mechanisms to clinical biomarkers and therapies","authors":"Haoxuan Wang , Xinzhe Chen , Yinghui Li , Shudan Xiao , Tianqi Teng , Sumin Yang , Kun Wang , Meihua Zhang","doi":"10.1016/j.ncrna.2025.08.006","DOIUrl":"10.1016/j.ncrna.2025.08.006","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 1-20"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 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.
{"title":"Exosome-like nanovesicles from Dunaliella salina efficient sequential Co-delivery of anti-PDL1 and miR-375 for enhancing gene/immune therapy","authors":"Zhaoyi Wei , Mengxi Zhu , Shan Li , Junling An , Yiwen Liu , Shuying Feng , Tingting Yang , Shegan Gao , Gaofeng Liang","doi":"10.1016/j.ncrna.2025.08.007","DOIUrl":"10.1016/j.ncrna.2025.08.007","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>A novel targeted drug delivery system based on exosome-like nanovesicles has been developed using the natural Marine single-celled salt <em>Dunaliella salina</em> (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 <em>in vitro</em> and the effects of engineered exosomes on esophageal cancer cells were further verified <em>in vivo</em>.</div></div><div><h3>Results</h3><div>The engineered DENV delivery system was prepared and characterized. It exhibited a uniform particle diameter (approximately 150 nm) with <em>in vitro</em> 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 <em>in vitro</em>. <em>In vivo</em> 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.</div></div><div><h3>Conclusions</h3><div>The potential of <em>Dunaliella salina</em> 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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 191-203"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}