Pub Date : 2025-02-22DOI: 10.1016/j.ncrna.2025.02.007
Heng Chen , Mengzhen Huang , Jiayi Li , Shanshan Zhang , Cuiyun Sun , Wenjun Luo , Lin Yu
Background
Alu-mediated p21 transcriptional regulator (APTR) overexpression is detected in different human cancers; however, few reports have investigated APTR gene amplification conditions. Furthermore, whether APTR amplification is related to glioma malignancy and the underlying mechanism remain unknown.
Methods
APTR amplification and expression levels in 153 glioma samples were analyzed using qPCR. Correlations between APTR and patient prognosis were evaluated using Kaplan-Meier survival and COX regression analyses. Both in vitro and in vivo phenotypic assays were performed to confirm the carcinogenic effects of APTR in glioblastoma (GBM) cells. RNA-sequencing and RNA immunoprecipitation and luciferase reporter assays were performed to confirm APTR as a competing endogenous RNA (ceRNA) and to identify the downstream axis of APTR.
Results
Our results suggest that APTR amplification and overexpression are novel independent diagnostic biomarkers for predicting poor prognosis in patients with gliomas. APTR knockdown significantly repressed the proliferation and invasion of GBM cells, both in vitro and in vivo. APTR was demonstrated to absorb miR-6734-5p and upregulate TCF7 and LEF1 expression. Taken together, these results suggest that APTR promotes the malignant phenotypes of GBM by inducing TCF7 and LEF1 expression.
Conclusion
We identified APTR as a novel prognostic biomarker in patients with gliomas and confirmed that APTR is a ceRNA that promotes glioma progression via the APTR/miR-6734-5p/TCF7/LEF1 axis.
{"title":"LncRNA APTR amplification serves as a potential glioma biomarker and promotes glioma progression via miR-6734-5p/ TCF7/LEF1 axis","authors":"Heng Chen , Mengzhen Huang , Jiayi Li , Shanshan Zhang , Cuiyun Sun , Wenjun Luo , Lin Yu","doi":"10.1016/j.ncrna.2025.02.007","DOIUrl":"10.1016/j.ncrna.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Alu-mediated p21 transcriptional regulator (<em>APTR</em>) overexpression is detected in different human cancers; however, few reports have investigated <em>APTR</em> gene amplification conditions. Furthermore, whether <em>APTR</em> amplification is related to glioma malignancy and the underlying mechanism remain unknown.</div></div><div><h3>Methods</h3><div><em>APTR</em> amplification and expression levels in 153 glioma samples were analyzed using qPCR. Correlations between APTR and patient prognosis were evaluated using Kaplan-Meier survival and COX regression analyses. Both <em>in vitro</em> and <em>in vivo</em> phenotypic assays were performed to confirm the carcinogenic effects of APTR in glioblastoma (GBM) cells. RNA-sequencing and RNA immunoprecipitation and luciferase reporter assays were performed to confirm APTR as a competing endogenous RNA (ceRNA) and to identify the downstream axis of APTR.</div></div><div><h3>Results</h3><div>Our results suggest that <em>APTR</em> amplification and overexpression are novel independent diagnostic biomarkers for predicting poor prognosis in patients with gliomas. APTR knockdown significantly repressed the proliferation and invasion of GBM cells, both <em>in vitro</em> and <em>in vivo</em>. APTR was demonstrated to absorb miR-6734-5p and upregulate TCF7 and LEF1 expression. Taken together, these results suggest that APTR promotes the malignant phenotypes of GBM by inducing TCF7 and LEF1 expression.</div></div><div><h3>Conclusion</h3><div>We identified APTR as a novel prognostic biomarker in patients with gliomas and confirmed that APTR is a ceRNA that promotes glioma progression via the APTR/miR-6734-5p/TCF7/LEF1 axis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 42-55"},"PeriodicalIF":5.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-21DOI: 10.1016/j.ncrna.2025.02.004
Yi-jing Liu , Hai-bing Miao , Shu Lin , Zhen Chen
This study found that in patients with SLE (n = 5), lethal (let)-7f-5p expression was significantly downregulated in peripheral blood mononuclear cells. Further, high-throughput RNA sequencing was used to mine the differential transcriptome expression in renal tissue exosomes of systemic lupus erythematosus (SLE)-prone mice, and bioinformatics was utilized to analyze non-coding RNAs and coding RNAs in exosomes for their possible roles in SLE. In renal tissues of MRL/lpr SLE-prone mice with exosomes and Pristane-induced SLE mice, we also demonstrated aberrant expression levels of microRNA (miRNA) let-7f-5p. Meanwhile, in the macrophage inflammation model, the expression levels of let-7f-5p were downregulated, that of guanylate binding protein (Gbp2 and Gbp7) were upregulated, and the inflammatory state of macrophages was alleviated following transfection with the let-7f-5p mimic. Co-culturing mesenchymal stem cells with a macrophage model of inflammation resulted in increased let-7f-5p expression and downregulated inflammatory factors, Gbp2 and Gbp7 expression in macrophages. Dual luciferase reporter gene assays confirmed that let-7f-5p directly binds to the 3′ UTR of Gbp7 to regulate its expression. Let-7f-5p regulation of the Gbp family is involved in SLE pathogenesis and is a biomarker associated with the inflammatory response with potential clinical applications.
{"title":"Exosomes derived let-7f-5p is a potential biomarker of SLE with anti-inflammatory function","authors":"Yi-jing Liu , Hai-bing Miao , Shu Lin , Zhen Chen","doi":"10.1016/j.ncrna.2025.02.004","DOIUrl":"10.1016/j.ncrna.2025.02.004","url":null,"abstract":"<div><div>This study found that in patients with SLE (n = 5), lethal (let)-7f-5p expression was significantly downregulated in peripheral blood mononuclear cells. Further, high-throughput RNA sequencing was used to mine the differential transcriptome expression in renal tissue exosomes of systemic lupus erythematosus (SLE)-prone mice, and bioinformatics was utilized to analyze non-coding RNAs and coding RNAs in exosomes for their possible roles in SLE. In renal tissues of MRL/lpr SLE-prone mice with exosomes and Pristane-induced SLE mice, we also demonstrated aberrant expression levels of microRNA (miRNA) let-7f-5p. Meanwhile, in the macrophage inflammation model, the expression levels of let-7f-5p were downregulated, that of guanylate binding protein (Gbp2 and Gbp7) were upregulated, and the inflammatory state of macrophages was alleviated following transfection with the let-7f-5p mimic. Co-culturing mesenchymal stem cells with a macrophage model of inflammation resulted in increased let-7f-5p expression and downregulated inflammatory factors, Gbp2 and Gbp7 expression in macrophages. Dual luciferase reporter gene assays confirmed that let-7f-5p directly binds to the 3′ UTR of Gbp7 to regulate its expression. Let-7f-5p regulation of the Gbp family is involved in SLE pathogenesis and is a biomarker associated with the inflammatory response with potential clinical applications.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 116-131"},"PeriodicalIF":5.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-21DOI: 10.1016/j.ncrna.2025.02.003
Andrei Gurau , Suguru Yamauchi , Kaitlyn Ecoff , Kristen P. Rodgers , James R. Eshleman , Charles Conover Talbot Jr , Peng Huang , Joshua Choi , Patrick M. Forde , Valsamo Anagnostou , Malcolm Brock , Yuping Mei
Background
A new therapeutic avenue combining Durvalumab with cisplatin-pemetrexed (Durva-CP) has delivered a promising outcome for previously untreated patients with unresectable malignant pleural mesothelioma (MPM) in clinical trials. However, the limited patient response to Durva-CP needs predictors to select optimal candidates and monitor the developed resistance. Protein functional effector sncRNA (pfeRNA) reveals a fundamental mechanism underlying the regulation of protein activity. The common mechanisms underlying durvalumab, cisplatin, and pemetrexed indicate that PD-L1 pfeRNAs (PDLpfeRNAs) are key molecules that control the treatment response.
Methods
We specified PDLpfeRNAs by sncRNA deep sequencing, confirmed their binding to PD-L1 by immunoprecipitation and reverse pull-down assays, and demonstrated their roles in controlling the interaction behaviors of PD1/L1 through quality-controlled drug development assays. Following the standards required for the CLIA-compliant LDT, we measured their expression levels in 60 plasma biospecimens from 30 unresectable MPM patients enrolled in the PrE0505 Phase II multicenter study. Using the Cox proportional hazards model and Kaplan-Meier analyses, we described their significance in predicting the treatment response of unresectable MPM patients administered Durva-CP as first-line therapy.
Results
Two PDLpfeRNAs, PDLpfeRNAa and PDLpfeRNAb, were characterized, confirmed to bind to PD-L1, and identified to control the interaction behaviors of PD-1/L1. Their plasma relative expression levels (REL) demonstrated significant prognostic value for both overall survival (p = 0.0019) and progression-free survival (p = 0.019), and the association remained significant after adjusting for histological subtype (HR 2.59, 95 % CI: 1.00–6.70, p = 0.050) and age (HR 1.03, 95 % CI: 0.98–1.07, p = 0.269).
Conclusions
Plasma PDLpfeRNAs are predictors of treatment response of unresectable MPM patients treated with Durva-CP as first-line therapy to select optimal candidates and monitor the developed resistance.
{"title":"PD-L1 pfeRNAs as blood-based predictors of treatment response of unresectable malignant pleural mesothelioma patients administered Durvalumab with cisplatin and pemetrexed as first-line therapy","authors":"Andrei Gurau , Suguru Yamauchi , Kaitlyn Ecoff , Kristen P. Rodgers , James R. Eshleman , Charles Conover Talbot Jr , Peng Huang , Joshua Choi , Patrick M. Forde , Valsamo Anagnostou , Malcolm Brock , Yuping Mei","doi":"10.1016/j.ncrna.2025.02.003","DOIUrl":"10.1016/j.ncrna.2025.02.003","url":null,"abstract":"<div><h3>Background</h3><div>A new therapeutic avenue combining Durvalumab with cisplatin-pemetrexed (Durva-CP) has delivered a promising outcome for previously untreated patients with unresectable malignant pleural mesothelioma (MPM) in clinical trials. However, the limited patient response to Durva-CP needs predictors to select optimal candidates and monitor the developed resistance. Protein functional effector sncRNA (pfeRNA) reveals a fundamental mechanism underlying the regulation of protein activity. The common mechanisms underlying durvalumab, cisplatin, and pemetrexed indicate that PD-L1 pfeRNAs (PDLpfeRNAs) are key molecules that control the treatment response.</div></div><div><h3>Methods</h3><div>We specified PDLpfeRNAs by sncRNA deep sequencing, confirmed their binding to PD-L1 by immunoprecipitation and reverse pull-down assays, and demonstrated their roles in controlling the interaction behaviors of PD1/L1 through quality-controlled drug development assays. Following the standards required for the CLIA-compliant LDT, we measured their expression levels in 60 plasma biospecimens from 30 unresectable MPM patients enrolled in the PrE0505 Phase II multicenter study. Using the Cox proportional hazards model and Kaplan-Meier analyses, we described their significance in predicting the treatment response of unresectable MPM patients administered Durva-CP as first-line therapy.</div></div><div><h3>Results</h3><div>Two PDLpfeRNAs, PDLpfeRNAa and PDLpfeRNAb, were characterized, confirmed to bind to PD-L1, and identified to control the interaction behaviors of PD-1/L1. Their plasma relative expression levels (REL) demonstrated significant prognostic value for both overall survival (p = 0.0019) and progression-free survival (p = 0.019), and the association remained significant after adjusting for histological subtype (HR 2.59, 95 % CI: 1.00–6.70, p = 0.050) and age (HR 1.03, 95 % CI: 0.98–1.07, p = 0.269).</div></div><div><h3>Conclusions</h3><div>Plasma PDLpfeRNAs are predictors of treatment response of unresectable MPM patients treated with Durva-CP as first-line therapy to select optimal candidates and monitor the developed resistance.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 34-41"},"PeriodicalIF":5.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
miR-135b, a microRNA, is consistently up-regulated in various cancer tissues and cells, promoting cancer progression. By inhibiting one or more target genes, miR-135b regulates phenotypes such as cancer growth, apoptosis, migration, invasion, drug resistance, and angiogenesis, establishing it as a critical driver of cancer progression. Additionally, miR-135b is regulated by various oncogenes and therapeutic drugs, highlighting its complexity and therapeutic potential. Significant progress has been made in understanding miR-135b's impact on cancer cell behavior, establishing it as a promising biomarker for cancer diagnosis and prognosis, as well as a potential target for future cancer therapies. However, despite the extensive research on this topic, there has been no comprehensive review summarizing its role and mechanisms across different cancer types. This review aims to provide a detailed overview of the biological characteristics of miR-135b, its regulatory targets, upstream signaling pathways, and its therapeutic potential, including its influence on cancer chemoresistance. The review also addresses key controversies surrounding miR-135b in cancer research, aiming to deepen the understanding of its role, promote the transformation of its clinical application, and provide a theoretical foundation for developing more effective cancer treatment strategies.
{"title":"miR-135b: A key role in cancer biology and therapeutic targets","authors":"Yingchun Shao , Shuangshuang Zhang , Yuxin Pan , Zhan Peng , Yinying Dong","doi":"10.1016/j.ncrna.2025.02.005","DOIUrl":"10.1016/j.ncrna.2025.02.005","url":null,"abstract":"<div><div>miR-135b, a microRNA, is consistently up-regulated in various cancer tissues and cells, promoting cancer progression. By inhibiting one or more target genes, miR-135b regulates phenotypes such as cancer growth, apoptosis, migration, invasion, drug resistance, and angiogenesis, establishing it as a critical driver of cancer progression. Additionally, miR-135b is regulated by various oncogenes and therapeutic drugs, highlighting its complexity and therapeutic potential. Significant progress has been made in understanding miR-135b's impact on cancer cell behavior, establishing it as a promising biomarker for cancer diagnosis and prognosis, as well as a potential target for future cancer therapies. However, despite the extensive research on this topic, there has been no comprehensive review summarizing its role and mechanisms across different cancer types. This review aims to provide a detailed overview of the biological characteristics of miR-135b, its regulatory targets, upstream signaling pathways, and its therapeutic potential, including its influence on cancer chemoresistance. The review also addresses key controversies surrounding miR-135b in cancer research, aiming to deepen the understanding of its role, promote the transformation of its clinical application, and provide a theoretical foundation for developing more effective cancer treatment strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 67-80"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-11DOI: 10.1016/j.ncrna.2025.02.002
Qianqian Wang , Peize Chen , Xiaorong Wang , Yueming Wu , Kaiguo Xia , Xiangyu Mu , Qiang Xuan , Jun Xiao , Yaohui He , Wen Liu , Xiaoyuan Song , Fei Sun
{"title":"Corrigendum to “piR-36249 and DHX36 together inhibit testicular cancer cells progression by upregulating OAS2” [Noncoding RNA Research 2023 8 (2) 174–186]","authors":"Qianqian Wang , Peize Chen , Xiaorong Wang , Yueming Wu , Kaiguo Xia , Xiangyu Mu , Qiang Xuan , Jun Xiao , Yaohui He , Wen Liu , Xiaoyuan Song , Fei Sun","doi":"10.1016/j.ncrna.2025.02.002","DOIUrl":"10.1016/j.ncrna.2025.02.002","url":null,"abstract":"","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 65-66"},"PeriodicalIF":5.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ncrna.2025.01.008
{"title":"List of reviewers in 2024","authors":"","doi":"10.1016/j.ncrna.2025.01.008","DOIUrl":"10.1016/j.ncrna.2025.01.008","url":null,"abstract":"","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 269-271"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ncrna.2024.12.003
Amal Ahmed Mohamed , Noha Nagah Amer , Noha Osama , Wael Hafez , Ali Elsaid Abdelrahman Ali , Mahmoud Maamoun Shaheen , Ayman Abd Alhady Alkhalegy , Eman Alsayed Abouahmed , Shamel Mohamed Soaida , Lamees A. Samy , Ahmed El-Kassas , Ivan Cherrez-Ojeda , Rehab R El-Awady
Objectives
Globally, hepatocellular Carcinoma (HCC) ranks seventh in women's cancer and fifth in men's cancer. Early identification can minimize mortality and morbidity. MicroRNAs and Toll-like receptors have been suggested as potential new biomarkers for HCC; Therefore, we explored Toll-like receptor 4 (TLR-4) and miRNA 15b-5p as new non-invasive HCC biomarkers and early detection approaches.
Methodology
In this case-control study, four primary groups were formed from 400 patients who participated in this study: 100 hepatitis C (HCV) patients without cirrhosis or HCC, 100 HCV with cirrhosis patients, 100 HCC and HCV patients, and 100 healthy controls. The HCC diagnosis was confirmed according to the American Association for the Study of Liver Disease (AASLD) Practice Guidelines. Triphasic computed tomography was used to assess the HCC tumor size. Real-time PCR was used to analyze miRNA 15b-5p and Toll-like receptor 4 (TLR-4) expression profiles.
Results
Significant diagnostic performance was achieved by miRNA 15b-5p in differentiating the HCC group from the control group, with 90 % sensitivity and 88 % specificity (AUC] 0.935, p < 0.001), while TLR-4 had moderate diagnostic performance with 85 % sensitivity and 86 % specificity (AUC:0.885, p < 0.001).
Conclusions
The ability of miR-15b-5p to recognize HCC was positive and it outperformed Toll-like receptor4. MiR-15b-5p has the potential to be a more precise and predictive biological marker for HCC than Toll-like receptor4. Future studies exploring different miRNAs and HCC cases from various etiologies are required to better understand the role of miRNAs in this disease and allow for more effective strategies.
{"title":"Expression of miR-15b-5p and toll-like receptor4 as potential novel diagnostic biomarkers for hepatitis C virus-induced hepatocellular carcinoma","authors":"Amal Ahmed Mohamed , Noha Nagah Amer , Noha Osama , Wael Hafez , Ali Elsaid Abdelrahman Ali , Mahmoud Maamoun Shaheen , Ayman Abd Alhady Alkhalegy , Eman Alsayed Abouahmed , Shamel Mohamed Soaida , Lamees A. Samy , Ahmed El-Kassas , Ivan Cherrez-Ojeda , Rehab R El-Awady","doi":"10.1016/j.ncrna.2024.12.003","DOIUrl":"10.1016/j.ncrna.2024.12.003","url":null,"abstract":"<div><h3>Objectives</h3><div>Globally, hepatocellular Carcinoma (HCC) ranks seventh in women's cancer and fifth in men's cancer. Early identification can minimize mortality and morbidity. MicroRNAs and Toll-like receptors have been suggested as potential new biomarkers for HCC; Therefore, we explored Toll-like receptor 4 (TLR-4) and miRNA 15b-5p as new non-invasive HCC biomarkers and early detection approaches.</div></div><div><h3>Methodology</h3><div>In this case-control study, four primary groups were formed from 400 patients who participated in this study: 100 hepatitis C (HCV) patients without cirrhosis or HCC, 100 HCV with cirrhosis patients, 100 HCC and HCV patients, and 100 healthy controls. The HCC diagnosis was confirmed according to the American Association for the Study of Liver Disease (AASLD) Practice Guidelines. Triphasic computed tomography was used to assess the HCC tumor size. Real-time PCR was used to analyze miRNA 15b-5p and Toll-like receptor 4 (TLR-4) expression profiles.</div></div><div><h3>Results</h3><div>Significant diagnostic performance was achieved by miRNA 15b-5p in differentiating the HCC group from the control group, with 90 % sensitivity and 88 % specificity (AUC] 0.935, p < 0.001), while TLR-4 had moderate diagnostic performance with 85 % sensitivity and 86 % specificity (AUC:0.885, p < 0.001).</div></div><div><h3>Conclusions</h3><div>The ability of miR-15b-5p to recognize HCC was positive and it outperformed Toll-like receptor4. MiR-15b-5p has the potential to be a more precise and predictive biological marker for HCC than Toll-like receptor4. Future studies exploring different miRNAs and HCC cases from various etiologies are required to better understand the role of miRNAs in this disease and allow for more effective strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 262-268"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.ncrna.2025.01.009
G. Zaccagnini , D. Baci , S. Tastsoglou , I. Cozza , A. Madè , C. Voellenkle , M. Nicoletti , C. Ruatti , M. Longo , L. Perani , C. Gaetano , A. Esposito , F. Martelli
Aortic stenosis, a common valvular heart disease, can lead to left ventricular pressure overload, triggering pro-fibrotic responses in the heart. miR-210 is a microRNA that responds to hypoxia and ischemia and plays a role in immune regulation and in cardiac remodeling upon myocardial infarction. This study investigated the effects of miR-210 on cardiac fibrosis caused by pressure overload.
Using a mouse model with inducible miR-210 over-expression, we subjected mice to transverse aortic constriction (TAC) to induce pressure overload. Mice with miR-210 over-expression developed eccentric hypertrophy, heightened expression of hypertrophic markers (Nppa and Nppb) and increased cross sectional area of cardiomyocytes, impacting the free wall of the left ventricle. These findings suggest that miR-210 worsens cardiac dysfunction. Furthermore, miR-210 over-expression led to a more robust and sustained inflammatory response in the heart, increased interstitial and perivascular fibrosis, and activation of myofibroblasts. miR-210 also promoted angiogenesis. In vitro, cardiac fibroblasts over-expressing miR-210 showed increased adhesion, wound healing and migration capacity.
Our results demonstrate that miR-210 contributes to adverse cardiac remodeling in response to pressure overload, including eccentric hypertrophy, inflammation, and fibrosis.
{"title":"miR-210 overexpression increases pressure overload-induced cardiac fibrosis","authors":"G. Zaccagnini , D. Baci , S. Tastsoglou , I. Cozza , A. Madè , C. Voellenkle , M. Nicoletti , C. Ruatti , M. Longo , L. Perani , C. Gaetano , A. Esposito , F. Martelli","doi":"10.1016/j.ncrna.2025.01.009","DOIUrl":"10.1016/j.ncrna.2025.01.009","url":null,"abstract":"<div><div>Aortic stenosis, a common valvular heart disease, can lead to left ventricular pressure overload, triggering pro-fibrotic responses in the heart. miR-210 is a microRNA that responds to hypoxia and ischemia and plays a role in immune regulation and in cardiac remodeling upon myocardial infarction. This study investigated the effects of miR-210 on cardiac fibrosis caused by pressure overload.</div><div>Using a mouse model with inducible miR-210 over-expression, we subjected mice to transverse aortic constriction (TAC) to induce pressure overload. Mice with miR-210 over-expression developed eccentric hypertrophy, heightened expression of hypertrophic markers (Nppa and Nppb) and increased cross sectional area of cardiomyocytes, impacting the free wall of the left ventricle. These findings suggest that miR-210 worsens cardiac dysfunction. Furthermore, miR-210 over-expression led to a more robust and sustained inflammatory response in the heart, increased interstitial and perivascular fibrosis, and activation of myofibroblasts. miR-210 also promoted angiogenesis. <em>In vitro</em>, cardiac fibroblasts over-expressing miR-210 showed increased adhesion, wound healing and migration capacity.</div><div>Our results demonstrate that miR-210 contributes to adverse cardiac remodeling in response to pressure overload, including eccentric hypertrophy, inflammation, and fibrosis.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 20-33"},"PeriodicalIF":5.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-27DOI: 10.1016/j.ncrna.2025.01.010
Jiandong Zhang , Lei Ma , Limin He , Quanxiao Xu , Yan Ding , Lidong Wang
Background
While radiation-induced lung injury decreases quality of life and suppresses efficacy of radiotherapy, to date, the relationship between radiation-induced lung injury and repair remains unclear. Our previous studies revealed that TNFRSF10B-RIPK1/RIPK3-MLKL signaling induces necroptosis of alveolar epithelial cells and potentiates radiation-induced lung injury. We also found that microRNA-541-3p is differentially expressed in radiation-damaged lungs. The connection between microRNA-541-3p, TNFRSF10B signaling, and TGFβ1 signaling is also unclear.
Objective
This study was performed to explore the regulatory effects of microRNA-541-3p on TNFRSF10B and TGFβ1 signaling.
Methods
Mouse alveolar epithelial cells were transfected with a vector expressing microRNA-541-3p to regulate expression of target genes. Flow cytometry, polymerase chain reaction, and western blotting were used to analyze cell necroptosis, target gene expression, and target protein expression, respectively.
Results
Overexpression of microRNA-541-3p positively regulated TNFRSF10B-RIPK1/RIPK3-MLKL signaling through Rac2 to induce cell necroptosis. MicroRNA-541-3p negatively regulates Rac2. MicroRNA-541-3p and Rac2 regulate the expression of Tgf-beta1 and its encoded proteins.
Conclusions
The Rac2 gene synchronously regulates TNFRSF10B-RIPK1/RIPK3-MLKL and TGFβ1 signaling. MicroRNA-541-3P/Rac2 act as mediators of radiation damage and repair signaling.
{"title":"MicroRNA-541-3p/Rac2 signaling bridges radiation-induced lung injury and repair","authors":"Jiandong Zhang , Lei Ma , Limin He , Quanxiao Xu , Yan Ding , Lidong Wang","doi":"10.1016/j.ncrna.2025.01.010","DOIUrl":"10.1016/j.ncrna.2025.01.010","url":null,"abstract":"<div><h3>Background</h3><div>While radiation-induced lung injury decreases quality of life and suppresses efficacy of radiotherapy, to date, the relationship between radiation-induced lung injury and repair remains unclear. Our previous studies revealed that TNFRSF10B-RIPK1/RIPK3-MLKL signaling induces necroptosis of alveolar epithelial cells and potentiates radiation-induced lung injury. We also found that microRNA-541-3p is differentially expressed in radiation-damaged lungs. The connection between microRNA-541-3p, TNFRSF10B signaling, and TGFβ1 signaling is also unclear.</div></div><div><h3>Objective</h3><div>This study was performed to explore the regulatory effects of microRNA-541-3p on TNFRSF10B and TGFβ1 signaling.</div></div><div><h3>Methods</h3><div>Mouse alveolar epithelial cells were transfected with a vector expressing microRNA-541-3p to regulate expression of target genes. Flow cytometry, polymerase chain reaction, and western blotting were used to analyze cell necroptosis, target gene expression, and target protein expression, respectively.</div></div><div><h3>Results</h3><div>Overexpression of microRNA-541-3p positively regulated TNFRSF10B-RIPK1/RIPK3-MLKL signaling through Rac2 to induce cell necroptosis. MicroRNA-541-3p negatively regulates Rac2. MicroRNA-541-3p and Rac2 regulate the expression of Tgf-beta1 and its encoded proteins.</div></div><div><h3>Conclusions</h3><div>The Rac2 gene synchronously regulates TNFRSF10B-RIPK1/RIPK3-MLKL and TGFβ1 signaling. MicroRNA-541-3P/Rac2 act as mediators of radiation damage and repair signaling.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 10-19"},"PeriodicalIF":5.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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