Pub Date : 2025-10-01Epub Date: 2025-05-23DOI: 10.1016/j.ncrna.2025.05.012
Federica Longo , Giuseppe Gattuso , Graziana Spoto , Daria Ricci , Anastasia Cristina Venera Vitale , Alessandro Lavoro , Saverio Candido , Massimo Libra , Luca Falzone
MicroRNAs (miRNAs) are important regulators of gene expression and their dysregulation is involved in various diseases, including tumors. Among these, colorectal cancer (CRC) is the result of both genetic and epigenetic alterations with miRNAs playing a key pathogenetic role. Although numerous studies have investigated the most frequently dysregulated miRNAs in CRC, there is still no consensus on the specific role of individual miRNAs in the mechanisms leading to tumorigenesis, tumor progression, and the development of chemoresistance. This lack of clarity highlights the need for a deeper understanding of miRNA functions in CRC. Therefore, this review aims to clarify the role of miRNAs in CRC by examining their involvement in major oncogenic pathways, highlighting key miRNAs implicated in the disease, and exploring their potential as diagnostic biomarkers and therapeutic targets. By providing a comprehensive overview, we hope to shed light on the complex and multifaceted roles of miRNAs in CRC, which could pave the way for more effective CRC monitoring and the development of miRNA-guided therapeutic strategies.
{"title":"The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications","authors":"Federica Longo , Giuseppe Gattuso , Graziana Spoto , Daria Ricci , Anastasia Cristina Venera Vitale , Alessandro Lavoro , Saverio Candido , Massimo Libra , Luca Falzone","doi":"10.1016/j.ncrna.2025.05.012","DOIUrl":"10.1016/j.ncrna.2025.05.012","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are important regulators of gene expression and their dysregulation is involved in various diseases, including tumors. Among these, colorectal cancer (CRC) is the result of both genetic and epigenetic alterations with miRNAs playing a key pathogenetic role. Although numerous studies have investigated the most frequently dysregulated miRNAs in CRC, there is still no consensus on the specific role of individual miRNAs in the mechanisms leading to tumorigenesis, tumor progression, and the development of chemoresistance. This lack of clarity highlights the need for a deeper understanding of miRNA functions in CRC. Therefore, this review aims to clarify the role of miRNAs in CRC by examining their involvement in major oncogenic pathways, highlighting key miRNAs implicated in the disease, and exploring their potential as diagnostic biomarkers and therapeutic targets. By providing a comprehensive overview, we hope to shed light on the complex and multifaceted roles of miRNAs in CRC, which could pave the way for more effective CRC monitoring and the development of miRNA-guided therapeutic strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 65-95"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220903","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 : 2025-10-01Epub Date: 2025-05-20DOI: 10.1016/j.ncrna.2025.05.010
Caroline R. Espada , Christian Anthon , Rubens D.M. Magalhães , José Carlos Quilles Junior , Natalia M.M. Teles , Fabiano S. Pais , Lissur A. Orsine , Letícia de Almeida , Tânia P.A. Defina , Adam Dowle , Jan Gorodkin , Pegine B. Walrad , Angela K. Cruz
Leishmania parasites alternate between hosts, facing environmental changes that demand rapid gene expression adaptation. Lacking canonical RNA polymerase II promoters, transcription in these eukaryotes is polycistronic, with gene regulation occurring post-transcriptionally. Although non-coding RNAs (ncRNAs) have been identified in Leishmania transcriptomes, their functions remain unclear. Recognizing RNA structure's importance, we performed a genome-wide alignment of L. braziliensis and related species, identifying conserved RNA structures, 38 of which overlap with known ncRNAs. One such ncRNA, lncRNA45, was functionally characterized. Using a knockout cell line, we demonstrated that lncRNA45 is crucial for parasite fitness. Reintroducing the wild type lncRNA45 restored fitness, while a version with a single nucleotide substitution in the structured region did not. This mutation also altered RNA-protein interactions. These findings suggest that lncRNA45's regulatory role and protein interactions rely on its secondary structure. This study highlights the significance of structured lncRNAs in Leishmania biology and their potential as therapeutic targets. Further research into these ncRNAs could uncover new parasite regulation mechanisms and inspire novel treatment strategies.
{"title":"Computational discovery of conserved RNA structures and functional characterization of a structured lncRNA in Leishmania braziliensis","authors":"Caroline R. Espada , Christian Anthon , Rubens D.M. Magalhães , José Carlos Quilles Junior , Natalia M.M. Teles , Fabiano S. Pais , Lissur A. Orsine , Letícia de Almeida , Tânia P.A. Defina , Adam Dowle , Jan Gorodkin , Pegine B. Walrad , Angela K. Cruz","doi":"10.1016/j.ncrna.2025.05.010","DOIUrl":"10.1016/j.ncrna.2025.05.010","url":null,"abstract":"<div><div><em>Leishmania</em> parasites alternate between hosts, facing environmental changes that demand rapid gene expression adaptation. Lacking canonical RNA polymerase II promoters, transcription in these eukaryotes is polycistronic, with gene regulation occurring post-transcriptionally. Although non-coding RNAs (ncRNAs) have been identified in <em>Leishmania</em> transcriptomes, their functions remain unclear. Recognizing RNA structure's importance, we performed a genome-wide alignment of <em>L. braziliensis</em> and related species, identifying conserved RNA structures, 38 of which overlap with known ncRNAs. One such ncRNA, <em>lncRNA45</em>, was functionally characterized. Using a knockout cell line, we demonstrated that <em>lncRNA45</em> is crucial for parasite fitness. Reintroducing the wild type <em>lncRNA45</em> restored fitness, while a version with a single nucleotide substitution in the structured region did not. This mutation also altered RNA-protein interactions. These findings suggest that <em>lncRNA45</em>'s regulatory role and protein interactions rely on its secondary structure. This study highlights the significance of structured lncRNAs in <em>Leishmania</em> biology and their potential as therapeutic targets. Further research into these ncRNAs could uncover new parasite regulation mechanisms and inspire novel treatment strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 51-64"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220902","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 : 2025-10-01Epub Date: 2025-06-09DOI: 10.1016/j.ncrna.2025.05.017
Tresa López-Royo , Laura Moreno-Martínez , Gabriel Rada , Sofía Macías-Redondo , Ana Cristina Calvo , Alberto García-Redondo , Raquel Manzano , Rosario Osta
Research in amyotrophic lateral sclerosis (ALS) faces major burdens, including the urgent need for sensitive and specific biomarkers, the identification of novel and effective therapeutic targets and a deeper understanding of the mechanisms driving the disease. In this line, long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their regulatory role in a variety of important biological processes such as RNA metabolism, neuroinflammation, apoptosis or proteostasis.
This study aims to elucidate the expression profile of 14 lncRNAs in both the SOD1G93A mouse model and ALS patients. Different stages of the disease (presymptomatic, symptomatic and terminal) and 3 regions of the central nervous system (CNS) differentially affected by ALS (spinal cord, brainstem and frontal cortex) were included in the experimental design.
In SOD1G93A mice, all 14 lncRNAs exhibited differential expression patterns influenced by sex, age, and region, except for Malat1, Neat1, and H19, which displayed consistent expression patterns (Malat1 was decreased, while Neat1 and H19 were increased). These patterns were most prominent in the spinal cord, where lncRNAs were overall down-regulated. In contrast, in the brainstem and frontal cortex, lncRNAs were predominantly up-regulated. Notably, Gas5 expression levels in frontal cortex and spinal cord at the terminal stage correlated with the onset and progression of motor coordination and strength decline. Additionally, three lncRNAs (Gas5, Neat1 and Myoparr) were found to significantly correlate with survival.
In human ALS samples, increased levels of NEAT1 and SNHG16 were observed in the brainstem, and of MEG3 and H19 in the frontal cortex, whereas MALAT1 levels were decreased in frontal cortex.
In conclusion, this work supports lncRNAs as promising candidates as novel players and potential biomarkers in ALS and highlights SOD1G93A mice as a good model to study lncRNAs in the CNS in the context of this disease.
{"title":"LncRNA levels in the central nervous system as novel potential players and biomarkers in amyotrophic lateral sclerosis","authors":"Tresa López-Royo , Laura Moreno-Martínez , Gabriel Rada , Sofía Macías-Redondo , Ana Cristina Calvo , Alberto García-Redondo , Raquel Manzano , Rosario Osta","doi":"10.1016/j.ncrna.2025.05.017","DOIUrl":"10.1016/j.ncrna.2025.05.017","url":null,"abstract":"<div><div>Research in amyotrophic lateral sclerosis (ALS) faces major burdens, including the urgent need for sensitive and specific biomarkers, the identification of novel and effective therapeutic targets and a deeper understanding of the mechanisms driving the disease. In this line, long non-coding RNAs (lncRNAs) have emerged as promising candidates due to their regulatory role in a variety of important biological processes such as RNA metabolism, neuroinflammation, apoptosis or proteostasis.</div><div>This study aims to elucidate the expression profile of 14 lncRNAs in both the SOD1<sup>G93A</sup> mouse model and ALS patients. Different stages of the disease (presymptomatic, symptomatic and terminal) and 3 regions of the central nervous system (CNS) differentially affected by ALS (spinal cord, brainstem and frontal cortex) were included in the experimental design.</div><div>In SOD1<sup>G93A</sup> mice, all 14 lncRNAs exhibited differential expression patterns influenced by sex, age, and region, except for Malat1, Neat1, and H19, which displayed consistent expression patterns (Malat1 was decreased, while Neat1 and H19 were increased). These patterns were most prominent in the spinal cord, where lncRNAs were overall down-regulated. In contrast, in the brainstem and frontal cortex, lncRNAs were predominantly up-regulated. Notably, <em>Gas5</em> expression levels in frontal cortex and spinal cord at the terminal stage correlated with the onset and progression of motor coordination and strength decline. Additionally, three lncRNAs (<em>Gas5</em>, <em>Neat1</em> and <em>Myoparr</em>) were found to significantly correlate with survival.</div><div>In human ALS samples, increased levels of <em>NEAT1</em> and <em>SNHG16</em> were observed in the brainstem, and of <em>MEG3</em> and <em>H19</em> in the frontal cortex, whereas <em>MALAT1</em> levels were decreased in frontal cortex.</div><div>In conclusion, this work supports lncRNAs as promising candidates as novel players and potential biomarkers in ALS and highlights SOD1<sup>G93A</sup> mice as a good model to study lncRNAs in the CNS in the context of this disease.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 145-155"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471691","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 : 2025-10-01Epub 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":"2025-10-01","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}
Pub Date : 2025-10-01Epub Date: 2025-05-30DOI: 10.1016/j.ncrna.2025.05.015
Yang Wang , Cong Wang , Xin Dai , Ge Liu , Xiaolong Gao , Junru Zhang
Aging is an inevitable physiological process that occurs in living organisms and has significant implications for health and disease. As the human lifespan extends, the functionality of organs gradually diminishes, leading to the emergence of various aging-related symptoms. While it is not feasible to completely halt the aging process, investigating key molecules involved in aging can help devise valid strategies to delay its progression. Circular RNAs (circRNAs) are a novel category of non-protein-coding RNAs and are abundant in cells. Their distinctive circular structure and diverse biological functions have garnered considerable attention from the scientific community. CircRNAs play a crucial role in regulating biological processes such as the cell cycle, apoptosis, and autophagy. They are implicated in various mechanisms, including cell signaling, influencing post-transcriptional regulation, and functioning as sponges for microRNAs (miRNAs), to modulate gene expression and impact cellular senescence. This research paper sets out to elucidate the mechanisms by which circRNAs regulate gene expression, epigenetic modifications, and cellular functions, as well as to assess their potential applications in aging-associated disorders.
{"title":"Deciphering the multifaceted role of circular RNA in aging: from molecular mechanisms to therapeutic potentials","authors":"Yang Wang , Cong Wang , Xin Dai , Ge Liu , Xiaolong Gao , Junru Zhang","doi":"10.1016/j.ncrna.2025.05.015","DOIUrl":"10.1016/j.ncrna.2025.05.015","url":null,"abstract":"<div><div>Aging is an inevitable physiological process that occurs in living organisms and has significant implications for health and disease. As the human lifespan extends, the functionality of organs gradually diminishes, leading to the emergence of various aging-related symptoms. While it is not feasible to completely halt the aging process, investigating key molecules involved in aging can help devise valid strategies to delay its progression. Circular RNAs (circRNAs) are a novel category of non-protein-coding RNAs and are abundant in cells. Their distinctive circular structure and diverse biological functions have garnered considerable attention from the scientific community. CircRNAs play a crucial role in regulating biological processes such as the cell cycle, apoptosis, and autophagy. They are implicated in various mechanisms, including cell signaling, influencing post-transcriptional regulation, and functioning as sponges for microRNAs (miRNAs), to modulate gene expression and impact cellular senescence. This research paper sets out to elucidate the mechanisms by which circRNAs regulate gene expression, epigenetic modifications, and cellular functions, as well as to assess their potential applications in aging-associated disorders.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 129-144"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254875","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}
Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.
{"title":"Upregulation of LINC02154 promotes esophageal cancer progression by enhancing cell cycling and epithelial-mesenchymal transition","authors":"Kotoha Shimote , Takeshi Niinuma , Hiroshi Kitajima , Kazuya Ishiguro , Eiichiro Yamamoto , Gota Sudo , Akira Yorozu , Mutsumi Toyota , Masahiro Kai , Masashi Idogawa , Hiromu Suzuki","doi":"10.1016/j.ncrna.2025.06.001","DOIUrl":"10.1016/j.ncrna.2025.06.001","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) play crucial roles in the progression of human malignancies; however, their involvement in esophageal cancer (ESCA) remains incompletely understood. In this study, we screened for lncRNAs upregulated in ESCA and identified 12 lncRNAs significantly upregulated in primary ESCA tumors. Among those, elevated LINC02154 expression correlated positively with advanced T stages. LINC02154 knockdown in ESCA cell lines suppressed cell proliferation and migration, while ectopic expression of LINC02154 enhanced colony formation. Depletion of LINC02154 suppressed genes involved in various oncogenic processes, including cell cycling, epithelial-mesenchymal transition (EMT), and metabolism. We also found that LINC02154 promotes EMT and enhances chemoresistance, at least in part, through suppression of miR-200b. Finally, RNA-pulldown and mass spectrometry analysis revealed that LINC02154 interacts with proteins involved in the cornified envelope or desmosome. These findings suggest that LINC02154 exerts oncogenic effects through modulation of multiple oncogenic signaling pathways in ESCA and that LINC02154 is a potential therapeutic target.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 107-116"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231637","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 : 2025-10-01Epub Date: 2025-05-28DOI: 10.1016/j.ncrna.2025.05.016
Chang-Luo Li , Jin-Kun Zhuang , Zhong Liu , Zhong-Run Huang , Chun Xiang , Qian-Yu Chen , Ze-Xin Chen , Zhong-Song Shi
Background
Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes.
Methods
MiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-h MCAO following reperfusion at 6 h. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated.
Results
MiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models.
Conclusions
MiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.
{"title":"MicroRNA-29a-5p attenuates hemorrhagic transformation and improves outcomes after mechanical reperfusion for acute ischemic stroke","authors":"Chang-Luo Li , Jin-Kun Zhuang , Zhong Liu , Zhong-Run Huang , Chun Xiang , Qian-Yu Chen , Ze-Xin Chen , Zhong-Song Shi","doi":"10.1016/j.ncrna.2025.05.016","DOIUrl":"10.1016/j.ncrna.2025.05.016","url":null,"abstract":"<div><h3>Background</h3><div>Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes.</div></div><div><h3>Methods</h3><div>MiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-h MCAO following reperfusion at 6 h. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated.</div></div><div><h3>Results</h3><div>MiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models.</div></div><div><h3>Conclusions</h3><div>MiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 96-106"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231636","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 : 2025-10-01Epub Date: 2025-05-28DOI: 10.1016/j.ncrna.2025.05.014
Gusai Elhassan , Xiangxue Bu , Jiaxin Liu , Shuai Hou , Jinsong Yan , Haixin Lei
Loss or decreased expression of lncRNA MEG3 is a frequent event in the progression of many different malignancies. Overexpression of MEG3 in breast cancer cell lines MCF7 or MDA-MB-231 prevented cell migration, whereas depletion of MEG3 in human mammary epithelial cell line MCF10A strikingly promoted cell migration. As RNA-protein interactions are vital for RNA to function, RNP assembled on MEG3 in vivo was purified using affinity purification followed by mass spectrometry, which revealed ∼600 proteins with the potential to interact with MEG3. Bioinformatic analysis on RNA-seq data from MCF7 with MEG3 overexpression and MCF10A with MEG3 depletion led to the identification of CXCR4 as the major downstream mediator negatively regulated by MEG3 that facilitated breast cancer cell migration. In addition, the chromatin regulator CTCF emerged as the MEG3-binding protein that might regulate CXCR4 expression after comparison of proteins presenting in MEG3 lncRNP to ChIP-seq data and GPSAdb data of CXCR4. Further evidence was provided to show CTCF upregulated the expression of CXCR4 at transcriptional level, whereas co-expression of MEG3 with CTCF abolished transcriptional activation of CXCR4. Overall, our study pinpoints the importance of MEG3/CTCF-CXCR4 axis in regulating migration of breast cancer cells and provides novel insight into the mechanism of lncRNA MEG3 in cancer development.
{"title":"LncRNA MEG3/CTCF-CXCR4 axis functions in the regulation of breast cancer cell migration","authors":"Gusai Elhassan , Xiangxue Bu , Jiaxin Liu , Shuai Hou , Jinsong Yan , Haixin Lei","doi":"10.1016/j.ncrna.2025.05.014","DOIUrl":"10.1016/j.ncrna.2025.05.014","url":null,"abstract":"<div><div>Loss or decreased expression of lncRNA MEG3 is a frequent event in the progression of many different malignancies. Overexpression of MEG3 in breast cancer cell lines MCF7 or MDA-MB-231 prevented cell migration, whereas depletion of MEG3 in human mammary epithelial cell line MCF10A strikingly promoted cell migration. As RNA-protein interactions are vital for RNA to function, RNP assembled on MEG3 <em>in vivo</em> was purified using affinity purification followed by mass spectrometry, which revealed ∼600 proteins with the potential to interact with MEG3. Bioinformatic analysis on RNA-seq data from MCF7 with MEG3 overexpression and MCF10A with MEG3 depletion led to the identification of CXCR4 as the major downstream mediator negatively regulated by MEG3 that facilitated breast cancer cell migration. In addition, the chromatin regulator CTCF emerged as the MEG3-binding protein that might regulate CXCR4 expression after comparison of proteins presenting in MEG3 lncRNP to ChIP-seq data and GPSAdb data of CXCR4. Further evidence was provided to show CTCF upregulated the expression of CXCR4 at transcriptional level, whereas co-expression of MEG3 with CTCF abolished transcriptional activation of CXCR4. Overall, our study pinpoints the importance of MEG3/CTCF-CXCR4 axis in regulating migration of breast cancer cells and provides novel insight into the mechanism of lncRNA MEG3 in cancer development.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"14 ","pages":"Pages 117-128"},"PeriodicalIF":5.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241990","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 : 2025-08-01Epub Date: 2025-05-08DOI: 10.1016/j.ncrna.2025.05.005
Christopher Kyriacou , Sung Hye Kim , Maria Arianoglou , Shabnam Bobdiwala , Margaret Pikovsky , Nina Parker , Jennifer Barcroft , Maya Al-Memar , Phillip R. Bennett , David A. MacIntyre , Tom Bourne , Vasso Terzidou
Background
Pregnancy of unknown location (PUL) is classified if an early pregnancy is not visualised on transvaginal ultrasonography (TVUS). Biomarkers currently used to triage PUL outcomes have varying accuracy. Delayed or missed diagnosis of ectopic pregnancies (EP) continue to cause significant morbidity and mortality. We investigated whether maternal plasma microRNAs (miRNAs) can predict and differentiate high-risk EP from viable (VIUP) or non-viable (NVIUP) intrauterine pregnancies.
Methods
Plasma was collected from women with PUL/EP (n = 120), mostly between four to eight weeks’ gestation, where outcomes of EP (n = 39), VIUP (n = 58) and NVIUP (miscarriage, n = 23) were determined using TVUS. Nanostring nCounter miRNA assay was used to examine the expression of ∼800 miRNAs in 22 women. Differentially expressed miRNAs were validated using RT-qPCR in 98 women.
Results
Nanostring nCounter miRNA assay identified 19 miRNAs which were expressed significantly higher in EP/NVIUP compared with VIUP. Two miRNAs were validated in a second, separate validation cohort using RT-qPCR: hsa-miR-21-5p in EP was 2.8-fold higher than in VIUP (p = 0.03, ROC AUC = 0.64), and hsa-miR-411-5p had 0.2-fold decreased expression (p = 0.02, ROC AUC = 0.66). Combining the divergent miRNAs as a ratio improved discrimination of EP from VIUP (p < 0.001, ROC AUC = 0.74).
Conclusion
Plasma miRNAs are differentially expressed in EP and VIUP and are detectable as early as four gestational weeks. Exploring miRNA targets may further understanding of EP pathophysiology, offering the potential to use miRNA as predictive and diagnostic markers in early pregnancy.
{"title":"Maternal plasma microRNAs as potential biomarkers for triaging pregnancies of unknown location and ectopic pregnancy diagnosis","authors":"Christopher Kyriacou , Sung Hye Kim , Maria Arianoglou , Shabnam Bobdiwala , Margaret Pikovsky , Nina Parker , Jennifer Barcroft , Maya Al-Memar , Phillip R. Bennett , David A. MacIntyre , Tom Bourne , Vasso Terzidou","doi":"10.1016/j.ncrna.2025.05.005","DOIUrl":"10.1016/j.ncrna.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Pregnancy of unknown location (PUL) is classified if an early pregnancy is not visualised on transvaginal ultrasonography (TVUS). Biomarkers currently used to triage PUL outcomes have varying accuracy. Delayed or missed diagnosis of ectopic pregnancies (EP) continue to cause significant morbidity and mortality. We investigated whether maternal plasma microRNAs (miRNAs) can predict and differentiate high-risk EP from viable (VIUP) or non-viable (NVIUP) intrauterine pregnancies.</div></div><div><h3>Methods</h3><div>Plasma was collected from women with PUL/EP (n = 120), mostly between four to eight weeks’ gestation, where outcomes of EP (n = 39), VIUP (n = 58) and NVIUP (miscarriage, n = 23) were determined using TVUS. Nanostring nCounter miRNA assay was used to examine the expression of ∼800 miRNAs in 22 women. Differentially expressed miRNAs were validated using RT-qPCR in 98 women.</div></div><div><h3>Results</h3><div>Nanostring nCounter miRNA assay identified 19 miRNAs which were expressed significantly higher in EP/NVIUP compared with VIUP. Two miRNAs were validated in a second, separate validation cohort using RT-qPCR: hsa-miR-21-5p in EP was 2.8-fold higher than in VIUP (<em>p</em> = 0.03, ROC AUC = 0.64), and hsa-miR-411-5p had 0.2-fold decreased expression (<em>p</em> = 0.02, ROC AUC = 0.66). Combining the divergent miRNAs as a ratio improved discrimination of EP from VIUP (<em>p</em> < 0.001, ROC AUC = 0.74).</div></div><div><h3>Conclusion</h3><div>Plasma miRNAs are differentially expressed in EP and VIUP and are detectable as early as four gestational weeks. Exploring miRNA targets may further understanding of EP pathophysiology, offering the potential to use miRNA as predictive and diagnostic markers in early pregnancy.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 162-173"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138850","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 : 2025-08-01Epub Date: 2025-04-08DOI: 10.1016/j.ncrna.2025.04.003
Lingyu Tang , Xuan Deng , Ming Guan , Liang Zhong
Chemotherapeutic efficacy in colorectal cancer (CRC) is significantly hindered by the development of drug resistance. Emerging evidence indicates that circular RNAs (circRNAs) play pivotal roles in various cancer-related biological processes. Nonetheless, the specific role of circRNAs in oxaliplatin resistance in CRC remains largely unexplored. In this study, hsa_circ_0076691 (circ76691) overexpression was observed in the oxaliplatin-resistant CRC group and could predict poor prognosis. Functional analyses revealed that circ76691 attenuates oxaliplatin-induced apoptosis both in vitro and in vivo, thereby contributing to enhanced oxaliplatin resistance. Mechanistically, circ76691 transcriptionally downregulates miR-589–3p expression and acts as a molecular sponge for miR-589–3p, sequestering it from its downstream targets. Notably, fibroblast growth factor 9 (FGF9), identified as a downstream inhibitory target of miR-589–3p, is subsequently upregulated due to circ76691 activity. Furthermore, circ76691 expression is transcriptionally induced by USF1 through direct binding to its promoter region. Collectively, these findings elucidate the USF1/circ76691/miR-589–3p/FGF9 axis in inhibiting oxaliplatin-induced apoptosis, suggesting circ76691 as a potential therapeutic target to enhance the efficacy of platinum-based therapy.
{"title":"USF1-activated hsa_circ_0076691 induces oxaliplatin resistance via facilitating FGF9 expression in miR-589-3p-dependent manners","authors":"Lingyu Tang , Xuan Deng , Ming Guan , Liang Zhong","doi":"10.1016/j.ncrna.2025.04.003","DOIUrl":"10.1016/j.ncrna.2025.04.003","url":null,"abstract":"<div><div>Chemotherapeutic efficacy in colorectal cancer (CRC) is significantly hindered by the development of drug resistance. Emerging evidence indicates that circular RNAs (circRNAs) play pivotal roles in various cancer-related biological processes. Nonetheless, the specific role of circRNAs in oxaliplatin resistance in CRC remains largely unexplored. In this study, hsa_circ_0076691 (circ76691) overexpression was observed in the oxaliplatin-resistant CRC group and could predict poor prognosis. Functional analyses revealed that circ76691 attenuates oxaliplatin-induced apoptosis both <em>in vitro</em> and <em>in vivo</em>, thereby contributing to enhanced oxaliplatin resistance. Mechanistically, circ76691 transcriptionally downregulates miR-589–3p expression and acts as a molecular sponge for miR-589–3p, sequestering it from its downstream targets. Notably, fibroblast growth factor 9 (FGF9), identified as a downstream inhibitory target of miR-589–3p, is subsequently upregulated due to circ76691 activity. Furthermore, circ76691 expression is transcriptionally induced by USF1 through direct binding to its promoter region. Collectively, these findings elucidate the USF1/circ76691/miR-589–3p/FGF9 axis in inhibiting oxaliplatin-induced apoptosis, suggesting circ76691 as a potential therapeutic target to enhance the efficacy of platinum-based therapy.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"13 ","pages":"Pages 15-28"},"PeriodicalIF":5.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837909","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号