Pub Date : 2025-12-02DOI: 10.1016/j.ncrna.2025.11.005
Yongbin Wang , Baicheng Ma , Jiashuo Qiu , Likun Yu , Jianjun Xiong , Qianfu Yu , Xingnuan Li , Haichun Liao , Youen Huang , Shan He
N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic RNA, and has increasingly been recognized as a critical regulator of gene expression at both the transcriptional and post-transcriptional levels. The m6A modification process is highly dynamic and reversible, governed by methyltransferase writers (e.g., METTL3, METTL14, WTAP), demethylase erasers (such as FTO and ALKBH5), and specific readers (including YTHDF and IGF2BP protein families) that interpret the modification and mediate its downstream effects. Accumulating evidence indicates that m6A-mediated regulation of non-coding RNAs (ncRNAs) plays a pivotal role in osteogenic differentiation, a process central to bone formation. Impaired osteogenesis, which contributes to decreased bone mass, is closely linked to the onset and progression of osteoporosis. This review summarizes recent progress on the interplay between m6A modification and ncRNAs in osteogenic differentiation, and outlines a regulatory framework, the m6A-ncRNA-target gene axis, that includes m6A modification, ncRNA interactions, and downstream signaling pathways, such as Wnt/β-catenin and BMP/Smad, and discusses their potential as biomarkers or therapeutic targets for osteoporosis, with the goal of providing new insights into the epigenetic mechanisms underlying osteoporosis and to identify potential molecular targets for future therapeutic strategies.
{"title":"The progress of m6A methylation-regulated non-coding RNAs in osteogenic differentiation and osteoporosis","authors":"Yongbin Wang , Baicheng Ma , Jiashuo Qiu , Likun Yu , Jianjun Xiong , Qianfu Yu , Xingnuan Li , Haichun Liao , Youen Huang , Shan He","doi":"10.1016/j.ncrna.2025.11.005","DOIUrl":"10.1016/j.ncrna.2025.11.005","url":null,"abstract":"<div><div>N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic RNA, and has increasingly been recognized as a critical regulator of gene expression at both the transcriptional and post-transcriptional levels. The m6A modification process is highly dynamic and reversible, governed by methyltransferase writers (e.g., METTL3, METTL14, WTAP), demethylase erasers (such as FTO and ALKBH5), and specific readers (including YTHDF and IGF2BP protein families) that interpret the modification and mediate its downstream effects. Accumulating evidence indicates that m6A-mediated regulation of non-coding RNAs (ncRNAs) plays a pivotal role in osteogenic differentiation, a process central to bone formation. Impaired osteogenesis, which contributes to decreased bone mass, is closely linked to the onset and progression of osteoporosis. This review summarizes recent progress on the interplay between m6A modification and ncRNAs in osteogenic differentiation, and outlines a regulatory framework, the m6A-ncRNA-target gene axis, that includes m6A modification, ncRNA interactions, and downstream signaling pathways, such as Wnt/β-catenin and BMP/Smad, and discusses their potential as biomarkers or therapeutic targets for osteoporosis, with the goal of providing new insights into the epigenetic mechanisms underlying osteoporosis and to identify potential molecular targets for future therapeutic strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 1-11"},"PeriodicalIF":4.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645799","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 : 2025-11-25DOI: 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.
{"title":"Integrative analysis of tissue and circulating miRNAs as biomarkers for progression and survival in hepatocellular carcinoma","authors":"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","doi":"10.1016/j.ncrna.2025.11.002","DOIUrl":"10.1016/j.ncrna.2025.11.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 167-177"},"PeriodicalIF":4.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614881","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 : 2025-11-08DOI: 10.1016/j.ncrna.2025.10.005
Simona De Summa , Letizia Porcelli , Giuseppe De Palma , Antonio Palazzo , Giuseppina Matera , Alessandro Caniglia , Roberta Di Fonte , Rosella Fasano , Francesco A. Zito , Stefania Tommasi , Simona Serratì , Amalia Azzariti
Prostate cancer (PCa) is the most frequently diagnosed malignancy among men and remains a leading cause of cancer-related death. Despite the widespread use of diagnostic tools such as PSA testing and Gleason scoring, these methods often fall short in accurately predicting tumor progression, highlighting the urgent need for reliable, non-invasive biomarkers to improve prognosis. In this study, we explored the potential of long non-coding RNAs (lncRNAs) as novel prognostic biomarkers for PCa. An initial in silico analysis of public datasets identified six lncRNAs differentially expressed in PCa tissues compared to healthy and adjacent non-tumor tissues. Of these, three were validated in a cohort of prostate cancer and benign prostatic hyperplasia (BPH) tissue samples. Notably, four lncRNAs showed expression levels that increased with higher Gleason scores, suggesting their potential as indicators of disease progression rather than early detection. To evaluate their applicability in a non-invasive setting, we assessed the expression of these lncRNAs in urinary extracellular vesicles (EVs). The results evidenced that Lnc-OPRK1-3 and lnc-SRSF6-1 are candidates as non-invasive prognostic biomarkers since they were detectable in urine and exhibited expression levels that correlate with advancing disease, specifically in the transition from Gleason score 3 + 3 to 4 + 3 and above. Their detection through urine-based liquid biopsy could support more precise patient stratification and suggest clinical decision-making. Further investigation is needed to validate their functional relevance and clinical utility.
{"title":"LncRNA expression in prostate cancer: From in silico analysis to urinary EV-based liquid biopsy for prognosis","authors":"Simona De Summa , Letizia Porcelli , Giuseppe De Palma , Antonio Palazzo , Giuseppina Matera , Alessandro Caniglia , Roberta Di Fonte , Rosella Fasano , Francesco A. Zito , Stefania Tommasi , Simona Serratì , Amalia Azzariti","doi":"10.1016/j.ncrna.2025.10.005","DOIUrl":"10.1016/j.ncrna.2025.10.005","url":null,"abstract":"<div><div>Prostate cancer (PCa) is the most frequently diagnosed malignancy among men and remains a leading cause of cancer-related death. Despite the widespread use of diagnostic tools such as PSA testing and Gleason scoring, these methods often fall short in accurately predicting tumor progression, highlighting the urgent need for reliable, non-invasive biomarkers to improve prognosis. In this study, we explored the potential of long non-coding RNAs (lncRNAs) as novel prognostic biomarkers for PCa. An initial <em>in silico</em> analysis of public datasets identified six lncRNAs differentially expressed in PCa tissues compared to healthy and adjacent non-tumor tissues. Of these, three were validated in a cohort of prostate cancer and benign prostatic hyperplasia (BPH) tissue samples. Notably, four lncRNAs showed expression levels that increased with higher Gleason scores, suggesting their potential as indicators of disease progression rather than early detection. To evaluate their applicability in a non-invasive setting, we assessed the expression of these lncRNAs in urinary extracellular vesicles (EVs). The results evidenced that Lnc-OPRK1-3 and lnc-SRSF6-1 are candidates as non-invasive prognostic biomarkers since they were detectable in urine and exhibited expression levels that correlate with advancing disease, specifically in the transition from Gleason score 3 + 3 to 4 + 3 and above. Their detection through urine-based liquid biopsy could support more precise patient stratification and suggest clinical decision-making. Further investigation is needed to validate their functional relevance and clinical utility.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 117-125"},"PeriodicalIF":4.7,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466253","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 : 2025-11-05DOI: 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.
{"title":"miR-6850 drives phenotypic changes and signaling in high grade serous ovarian cancer","authors":"Kamil Filipek , Daniela Pollutri , Ivana Kurelac , Giuseppe Gasparre , Marianna Penzo","doi":"10.1016/j.ncrna.2025.10.004","DOIUrl":"10.1016/j.ncrna.2025.10.004","url":null,"abstract":"<div><div>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, <em>MIR6850</em> 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.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 104-116"},"PeriodicalIF":4.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466251","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 : 2025-10-14DOI: 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.
{"title":"Keratinocyte-specific long non-coding RNA NR037661 controls alternative splicing of ANGPTL4 to induce keratinocyte differentiation","authors":"Chunxiao Li , Qinyuan Zhu , Xinhang Cao , Dandan Xiao , Hui Yang , Xiang Kong , Ziyu Wang , Mingzhe Ma , Yangbai Sun","doi":"10.1016/j.ncrna.2025.10.003","DOIUrl":"10.1016/j.ncrna.2025.10.003","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>Our findings illuminate a novel regulatory mechanism underlying keratinocyte differentiation, potentially revealing new therapeutic targets for skin diseases.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 93-103"},"PeriodicalIF":4.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418116","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 : 2025-10-10DOI: 10.1016/j.ncrna.2025.10.002
Xiuping Wang , Zhendong Yao , Yu Liu , Boneng Mao , Chen Shao , Shihe Shao
Background
Circular RNAs (circRNAs) have been implicated in developing gastric cancer (GC). However, the role of circMRPL35 in GC remains unknown.
Methods
This study identified differentially expressed circMRPL35 using gene expression profiles GSE78092, GSE131414, and GSE100170. RNA R enzyme and RNA FISH assays were used to explore the origin, cyclization site, and cellular localization of circMRPL35. The functions of circMRPL35, miR-6809-3p, and ZNF90 in GC cells were evaluated through loss- and gain-of-function experiments. The epithelial-mesenchymal transition (EMT) process and the TGF-β1/SMAD signaling pathway were analyzed using Western blot and immunofluorescence assays. Subcutaneous tumor models in nude mice were utilized to evaluate the impact of circMRPL35 on GC cells. The interactions among circMRPL35, miR-6809-3p, and ZNF90 were confirmed through luciferase reporter and rescue assays.
Results
The study demonstrated that circMRPL35, present in the cytoplasm and nucleus of MGC-803 and HGC-27 cells, originates from the cyclization of exons 4 and 5 on chromosome 2. In GC tissues and cells, circMRPL35 and ZNF90 were upregulated, while miR-6809-3p was downregulated. circMRPL35 and ZNF90 enhanced cell mobility and invasion and suppressed apoptosis by modulating the EMT process and TGF-β1/SMAD2/3 signaling pathway; conversely, miR-6809-3p exhibited the opposite effects. Mechanistically, circMRPL35 sponges miR-6809-3p to regulate ZNF90, thereby enhancing the phenotype of GC cells.
Conclusions
These results indicate that circMRPL35 acts as an oncogenic driver via the miR-6809-3p/ZNF90 axis, affecting the EMT process and the TGF-β1/SMAD2/3 signaling pathway to promote GC progression.
{"title":"circMRPL35 promotes gastric cancer progression through the miR-6809-3p/ZNF90 axis and affects the EMT process and TGF-β1/SMAD2/3 signaling","authors":"Xiuping Wang , Zhendong Yao , Yu Liu , Boneng Mao , Chen Shao , Shihe Shao","doi":"10.1016/j.ncrna.2025.10.002","DOIUrl":"10.1016/j.ncrna.2025.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNAs (circRNAs) have been implicated in developing gastric cancer (GC). However, the role of circMRPL35 in GC remains unknown.</div></div><div><h3>Methods</h3><div>This study identified differentially expressed circMRPL35 using gene expression profiles GSE78092, GSE131414, and GSE100170. RNA R enzyme and RNA FISH assays were used to explore the origin, cyclization site, and cellular localization of circMRPL35. The functions of circMRPL35, miR-6809-3p, and ZNF90 in GC cells were evaluated through loss- and gain-of-function experiments. The epithelial-mesenchymal transition (EMT) process and the TGF-β1/SMAD signaling pathway were analyzed using Western blot and immunofluorescence assays. Subcutaneous tumor models in nude mice were utilized to evaluate the impact of circMRPL35 on GC cells. The interactions among circMRPL35, miR-6809-3p, and ZNF90 were confirmed through luciferase reporter and rescue assays.</div></div><div><h3>Results</h3><div>The study demonstrated that circMRPL35, present in the cytoplasm and nucleus of MGC-803 and HGC-27 cells, originates from the cyclization of exons 4 and 5 on chromosome 2. In GC tissues and cells, circMRPL35 and ZNF90 were upregulated, while miR-6809-3p was downregulated. circMRPL35 and ZNF90 enhanced cell mobility and invasion and suppressed apoptosis by modulating the EMT process and TGF-β1/SMAD2/3 signaling pathway; conversely, miR-6809-3p exhibited the opposite effects. Mechanistically, circMRPL35 sponges miR-6809-3p to regulate ZNF90, thereby enhancing the phenotype of GC cells.</div></div><div><h3>Conclusions</h3><div>These results indicate that circMRPL35 acts as an oncogenic driver via the miR-6809-3p/ZNF90 axis, affecting the EMT process and the TGF-β1/SMAD2/3 signaling pathway to promote GC progression.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 79-92"},"PeriodicalIF":4.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418117","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 : 2025-10-10DOI: 10.1016/j.ncrna.2025.09.008
Mohammad A. Al Smadi , Haidar Haidar , Albert Salas-Huetos , Ulrike Fischer , Hashim Abdul-Khaliq , Eckart Meese , Masood Abu-Halima
Background
Sperm quality defined by motility and morphology has critical implications for fertility and pregnancy outcomes. Small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), play regulatory roles and may reflect underlying sperm function. This study aimed to identify small RNA types in sperm based on motility and morphology, examine their correlation with sperm and clinical parameters, and develop diagnostic tools to predict pregnancy outcomes.
Methods
A total of 98 male partners of couples undergoing infertility treatment were included. Thirteen males provided 39 sperm samples categorized into three groups based on quality: A (good), B (intermediate), and C (poor), each with 1500 individually selected sperm. Additionally, 85 males contributed purified sperm samples with various spermatogenic impairments. Small RNA sequencing was performed followed by RT-qPCR validation.
Results
Small RNA sequencing revealed a diverse RNA landscape in sperm, with long non-coding RNA (lncRNA) being the most abundant. Regulatory RNAs such as miRNAs and piRNAs were present at varying levels. Differential expression analysis identified 16 miRNAs and 37 piRNAs significantly different between groups A and C. Strong correlations were observed between miRNA/piRNA expression and sperm motility and morphology in groups A and C, but not in group B. miRNA expression levels were associated with sperm quality and pregnancy outcomes, including embryo quality, β-hCG levels, and live birth. Notably, hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p were linked to sperm impairments and hormonal markers (β-hCG, FSH, and LH). Higher expression of these miRNAs was associated with negative β-hCG outcomes and poor IVF prognosis. Lower expression of hsa-miR-15b-5p and hsa-miR-20a-5p was found in G1 embryos compared to G2 embryos. These miRNAs were also significantly correlated with live birth outcomes: higher expression was linked to failed IVF, while lower expression was linked to successful live births. Diagnostic validation showed AUCs of 0.76, 0.71, and 0.74 for hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p, respectively. A combined model yielded an AUC of 0.75.
Conclusion
These findings suggest that hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p could serve as potential biomarkers for assessing sperm quality and predicting pregnancy outcomes.
{"title":"Small RNA sequencing in individually selected sperm: Biomarkers for male subfertility and predictors of pregnancy success","authors":"Mohammad A. Al Smadi , Haidar Haidar , Albert Salas-Huetos , Ulrike Fischer , Hashim Abdul-Khaliq , Eckart Meese , Masood Abu-Halima","doi":"10.1016/j.ncrna.2025.09.008","DOIUrl":"10.1016/j.ncrna.2025.09.008","url":null,"abstract":"<div><h3>Background</h3><div>Sperm quality defined by motility and morphology has critical implications for fertility and pregnancy outcomes. Small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), play regulatory roles and may reflect underlying sperm function. This study aimed to identify small RNA types in sperm based on motility and morphology, examine their correlation with sperm and clinical parameters, and develop diagnostic tools to predict pregnancy outcomes.</div></div><div><h3>Methods</h3><div>A total of 98 male partners of couples undergoing infertility treatment were included. Thirteen males provided 39 sperm samples categorized into three groups based on quality: A (good), B (intermediate), and C (poor), each with 1500 individually selected sperm. Additionally, 85 males contributed purified sperm samples with various spermatogenic impairments. Small RNA sequencing was performed followed by RT-qPCR validation.</div></div><div><h3>Results</h3><div>Small RNA sequencing revealed a diverse RNA landscape in sperm, with long non-coding RNA (lncRNA) being the most abundant. Regulatory RNAs such as miRNAs and piRNAs were present at varying levels. Differential expression analysis identified 16 miRNAs and 37 piRNAs significantly different between groups A and C. Strong correlations were observed between miRNA/piRNA expression and sperm motility and morphology in groups A and C, but not in group B. miRNA expression levels were associated with sperm quality and pregnancy outcomes, including embryo quality, β-hCG levels, and live birth. Notably, hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p were linked to sperm impairments and hormonal markers (β-hCG, FSH, and LH). Higher expression of these miRNAs was associated with negative β-hCG outcomes and poor IVF prognosis. Lower expression of hsa-miR-15b-5p and hsa-miR-20a-5p was found in G1 embryos compared to G2 embryos. These miRNAs were also significantly correlated with live birth outcomes: higher expression was linked to failed IVF, while lower expression was linked to successful live births. Diagnostic validation showed AUCs of 0.76, 0.71, and 0.74 for hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p, respectively. A combined model yielded an AUC of 0.75.</div></div><div><h3>Conclusion</h3><div>These findings suggest that hsa-miR-15b-5p, hsa-miR-19a-5p, and hsa-miR-20a-5p could serve as potential biomarkers for assessing sperm quality and predicting pregnancy outcomes.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 126-143"},"PeriodicalIF":4.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520423","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 : 2025-10-09DOI: 10.1016/j.ncrna.2025.10.001
Jing Ren , Huiqiong Zou , Siyu Sun , Shan Chen , Rui He , Qianbing Zhou , Jun Tao , Junying Yang
Background
Porphyromonas gingivalis lipopolysaccharide (P.g-LPS), a key virulence factor in periodontitis, contributes to systemic vascular diseases, notably atherosclerosis. MicroRNA-21 (miR-21), a critical post-transcriptional regulator, influences inflammation and vascular pathology, but its role in endothelial responses to P.g-LPS remains unclear.
Methods
Gingival biopsies from eight patients with periodontitis and eight healthy controls were analyzed using immunofluorescence co-labeling for Cluster of Differentiation 31 (CD31) with TUNEL or Interleukin-6 (IL-6) to assess endothelial apoptosis and inflammation. MiR-21 levels were quantified using quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Human umbilical vein endothelial cells (HUVECs) were treated with P.g-LPS and transfected with miR-21 mimics or inhibitors. Apoptosis, proliferation, and migration were evaluated by flow cytometry, Cell Counting Kit-8 (CCK-8) assay, and wound healing analysis, respectively. Western blotting and Enzyme-Linked Immunosorbent Assay(ELISA) measured inflammatory and apoptotic markers. Luciferase reporter assays confirmed that PDCD4 was a direct target of miR-21, and the effects of Programmed Cell Death 4(PDCD4) knockdown on Nuclear Factor kappa B (NF-κB)/Inducible Nitric Oxide Synthase (iNOS)/Nitric Oxide (NO) signaling were examined.
Results
Endothelial cells from patients with periodontitis exhibited increased apoptosis and inflammation. P.g-LPS significantly reduced miR-21 expression in HUVECs. MiR-21 inhibition exacerbated apoptosis and inflammatory mediator expression, while suppressing proliferation and migration.MiR-21 overexpression mitigated these effects. PDCD4 was validated as a direct miR-21 target. Suppression of miR-21 enhanced NF-κB/iNOS/NO activation, and PDCD4 knockdown attenuated this pathway, indicating a regulatory mechanism.
Conclusion
MiR-21 acts as a protective regulator against P.g-LPS-induced endothelial injury by targeting PDCD4 and modulating the NF-κB/iNOS/NO pathway, thereby reducing inflammation and apoptosis. These findings indicate that miR-21 is a potential therapeutic target for vascular complications associated with chronic inflammatory diseases like periodontitis.
{"title":"MiR-21 modulates P.g-LPS induced apoptosis and inflammatory response in HUVECs via NF-κB/iNOS/NO pathway by targeting PDCD4","authors":"Jing Ren , Huiqiong Zou , Siyu Sun , Shan Chen , Rui He , Qianbing Zhou , Jun Tao , Junying Yang","doi":"10.1016/j.ncrna.2025.10.001","DOIUrl":"10.1016/j.ncrna.2025.10.001","url":null,"abstract":"<div><h3>Background</h3><div><em>Porphyromonas gingivalis</em> lipopolysaccharide (<em>P.g-</em>LPS), a key virulence factor in periodontitis, contributes to systemic vascular diseases, notably atherosclerosis. MicroRNA-21 (miR-21), a critical post-transcriptional regulator, influences inflammation and vascular pathology, but its role in endothelial responses to <em>P.g-</em>LPS remains unclear.</div></div><div><h3>Methods</h3><div>Gingival biopsies from eight patients with periodontitis and eight healthy controls were analyzed using immunofluorescence co-labeling for Cluster of Differentiation 31 (CD31) with TUNEL or Interleukin-6 (IL-6) to assess endothelial apoptosis and inflammation. MiR-21 levels were quantified using quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). Human umbilical vein endothelial cells (HUVECs) were treated with <em>P.g-</em>LPS and transfected with miR-21 mimics or inhibitors. Apoptosis, proliferation, and migration were evaluated by flow cytometry, Cell Counting Kit-8 (CCK-8) assay, and wound healing analysis, respectively. Western blotting and Enzyme-Linked Immunosorbent Assay(ELISA) measured inflammatory and apoptotic markers. Luciferase reporter assays confirmed that PDCD4 was a direct target of miR-21, and the effects of Programmed Cell Death 4(PDCD4) knockdown on Nuclear Factor kappa B (NF-κB)/Inducible Nitric Oxide Synthase (iNOS)/Nitric Oxide (NO) signaling were examined.</div></div><div><h3>Results</h3><div>Endothelial cells from patients with periodontitis exhibited increased apoptosis and inflammation. <em>P.g-</em>LPS significantly reduced miR-21 expression in HUVECs. MiR-21 inhibition exacerbated apoptosis and inflammatory mediator expression, while suppressing proliferation and migration.MiR-21 overexpression mitigated these effects. PDCD4 was validated as a direct miR-21 target. Suppression of miR-21 enhanced NF-κB/iNOS/NO activation, and PDCD4 knockdown attenuated this pathway, indicating a regulatory mechanism.</div></div><div><h3>Conclusion</h3><div>MiR-21 acts as a protective regulator against <em>P.g-</em>LPS-induced endothelial injury by targeting PDCD4 and modulating the NF-κB/iNOS/NO pathway, thereby reducing inflammation and apoptosis. These findings indicate that miR-21 is a potential therapeutic target for vascular complications associated with chronic inflammatory diseases like periodontitis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"16 ","pages":"Pages 144-155"},"PeriodicalIF":4.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520422","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.2025.09.009
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}
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