Pub Date : 2025-03-05DOI: 10.1016/j.ncrna.2025.03.004
Victoria Cairoli , Daniel Valle-Millares , Pablo Ryan , Lourdes Dominguez , Luz Martín-Carbonero , Ignacio De los Santos , Elena De Matteo , Beatriz Ameigeiras , Marcela De Sousa , Verónica Briz , María V. Preciado , Amanda Fernández-Rodriguez , Pamela Valva
Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis.
Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F < 2) and significant (F ≥ 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F ≥ 2 and F < 2). Dysregulated biological pathways were subsequently analyzed in silico for the following groups: i) all patients; ii) HCV+; and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F ≥ 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis.
With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F ≥ 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833).
In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F ≥ 2 (AUROC = 0.936).
With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4508, hsa-miR-122-5p, hsa-miR-451a, hsa-miR-1290, hsa-miR-1246, hsa-miR-107, hsa-miR-15b-5p, hsa-miR-194-5p, hsa-miR-22-5p, hsa-miR-20b-5p, hsa-miR-142-5p, hsa-miR-328-3p, hsa-miR-335-3p, hsa-miR-125a-5p, hsa-miR-423-3p, hsa-let-7d-3p, hsa-miR-128-3p, hsa-miR-10a-5p) were recognized that regulate RNA silencing processes. In this case, hsa-miR-423-3p and hsa-miR-128-3p showed outstanding diagnostic performances (AUROC > 0.900).
Distinct EVs-miRNA profiles were identified in patients with varying liver fibrosis stages, both in the overall CHC cohort and within HCV+ and HCV+/HIV+ subgroups. These specific miRNA signatures would allow the elucidation of potential mechanisms involved in clinical evolution and identification of specific biomarkers of unfavorable progression, plausible to be used in a diagnostic panel. Furthermore, the developed score demonstrates the ability to discriminate within the CHC group those i
{"title":"Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study","authors":"Victoria Cairoli , Daniel Valle-Millares , Pablo Ryan , Lourdes Dominguez , Luz Martín-Carbonero , Ignacio De los Santos , Elena De Matteo , Beatriz Ameigeiras , Marcela De Sousa , Verónica Briz , María V. Preciado , Amanda Fernández-Rodriguez , Pamela Valva","doi":"10.1016/j.ncrna.2025.03.004","DOIUrl":"10.1016/j.ncrna.2025.03.004","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis.</div><div>Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F < 2) and significant (F ≥ 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F ≥ 2 and F < 2). Dysregulated biological pathways were subsequently analyzed <em>in silico</em> for the following groups: i) all patients; ii) HCV+; and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F ≥ 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis.</div><div>With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F ≥ 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833).</div><div>In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F ≥ 2 (AUROC = 0.936).</div><div>With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4508, hsa-miR-122-5p, hsa-miR-451a, hsa-miR-1290, hsa-miR-1246, hsa-miR-107, hsa-miR-15b-5p, hsa-miR-194-5p, hsa-miR-22-5p, hsa-miR-20b-5p, hsa-miR-142-5p, hsa-miR-328-3p, hsa-miR-335-3p, hsa-miR-125a-5p, hsa-miR-423-3p, hsa-let-7d-3p, hsa-miR-128-3p, hsa-miR-10a-5p) were recognized that regulate RNA silencing processes. In this case, hsa-miR-423-3p and hsa-miR-128-3p showed outstanding diagnostic performances (AUROC > 0.900).</div><div>Distinct EVs-miRNA profiles were identified in patients with varying liver fibrosis stages, both in the overall CHC cohort and within HCV+ and HCV+/HIV+ subgroups. These specific miRNA signatures would allow the elucidation of potential mechanisms involved in clinical evolution and identification of specific biomarkers of unfavorable progression, plausible to be used in a diagnostic panel. Furthermore, the developed score demonstrates the ability to discriminate within the CHC group those i","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 132-140"},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643439","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 : 2025-03-03DOI: 10.1016/j.ncrna.2025.03.001
Li Dong , Haicui Wu , Fanghua Qi , Yuan Xu , Wen Chen , Yuqi Wang , Pingping Cai
As the earliest aging organ in the reproductive system, the ovary has both reproductive and endocrine functions, which are closely related to overall female health. The exact pathogenesis of ovarian aging (OA) remains incompletely understood, with granulosa cells (GCs) dysfunction playing a significant role in this process. Recent advancements in research and biotechnology have highlighted the importance of non-coding RNAs (ncRNAs), including micro RNAs, long non-coding RNAs, and circular RNAs, in regulating the biological functions of GCs through gene expression modulation. This paper provides a comprehensive overview of the role of ncRNAs in various cellular functions such as apoptosis, autophagy, proliferation, and steroid synthesis in GCs, and explores the underlying regulatory mechanisms. Additionally, the therapeutic potential of ncRNAs, particularly those carried by exosomes derived from mesenchymal stem cells, in delaying OA is discussed. Understanding the regulatory mechanisms of ncRNAs in GC function and the current progress in this field is crucial for identifying effective biomarkers and therapeutic targets, ultimately aiding in the early diagnosis, prognostic assessment, and individualized treatment of OA.
{"title":"Non-coding RNA-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions","authors":"Li Dong , Haicui Wu , Fanghua Qi , Yuan Xu , Wen Chen , Yuqi Wang , Pingping Cai","doi":"10.1016/j.ncrna.2025.03.001","DOIUrl":"10.1016/j.ncrna.2025.03.001","url":null,"abstract":"<div><div>As the earliest aging organ in the reproductive system, the ovary has both reproductive and endocrine functions, which are closely related to overall female health. The exact pathogenesis of ovarian aging (OA) remains incompletely understood, with granulosa cells (GCs) dysfunction playing a significant role in this process. Recent advancements in research and biotechnology have highlighted the importance of non-coding RNAs (ncRNAs), including micro RNAs, long non-coding RNAs, and circular RNAs, in regulating the biological functions of GCs through gene expression modulation. This paper provides a comprehensive overview of the role of ncRNAs in various cellular functions such as apoptosis, autophagy, proliferation, and steroid synthesis in GCs, and explores the underlying regulatory mechanisms. Additionally, the therapeutic potential of ncRNAs, particularly those carried by exosomes derived from mesenchymal stem cells, in delaying OA is discussed. Understanding the regulatory mechanisms of ncRNAs in GC function and the current progress in this field is crucial for identifying effective biomarkers and therapeutic targets, ultimately aiding in the early diagnosis, prognostic assessment, and individualized treatment of OA.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 102-115"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592784","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 : 2025-03-03DOI: 10.1016/j.ncrna.2025.03.003
Yanfang Lu , Anqi Chen , Mengxiao Liao , Ruiyang Tao , Shubo Wen , Suhua Zhang , Chengtao Li
Age estimation is a critical aspect of human identification. Traditional methods, reliant on morphological examinations, are often suitable for living subjects. However, there are relatively few studies on age estimation based on biological samples, such as blood. Recent advancements have concentrated on DNA methylation for forensic age prediction. However, to explore further possibilities, this study investigated microRNAs (miRNAs) as alternative molecular markers for age estimation. Peripheral blood samples from 127 healthy individuals were analyzed for miRNA expression using small RNA sequencing. Lasso regression selected 103 candidate miRNAs, and Shapley additive explanations (SHAP) analysis identified 38 key miRNAs significant for age prediction. Five machine learning models were developed, with the elastic net model achieving the best performance (MAE of 4.08 years) on the testing set, surpassing current miRNA age estimation results. Additionally, we observed significant changes in the expression levels of miRNAs in healthy individuals aged 48–52 years. This study demonstrated the potential of blood miRNA biomarkers in age prediction and provides a set of miRNA markers for developing more accurate age prediction methods.
{"title":"Development of a microRNA-Based age estimation model using whole-blood microRNA expression profiling","authors":"Yanfang Lu , Anqi Chen , Mengxiao Liao , Ruiyang Tao , Shubo Wen , Suhua Zhang , Chengtao Li","doi":"10.1016/j.ncrna.2025.03.003","DOIUrl":"10.1016/j.ncrna.2025.03.003","url":null,"abstract":"<div><div>Age estimation is a critical aspect of human identification. Traditional methods, reliant on morphological examinations, are often suitable for living subjects. However, there are relatively few studies on age estimation based on biological samples, such as blood. Recent advancements have concentrated on DNA methylation for forensic age prediction. However, to explore further possibilities, this study investigated microRNAs (miRNAs) as alternative molecular markers for age estimation. Peripheral blood samples from 127 healthy individuals were analyzed for miRNA expression using small RNA sequencing. Lasso regression selected 103 candidate miRNAs, and Shapley additive explanations (SHAP) analysis identified 38 key miRNAs significant for age prediction. Five machine learning models were developed, with the elastic net model achieving the best performance (MAE of 4.08 years) on the testing set, surpassing current miRNA age estimation results. Additionally, we observed significant changes in the expression levels of miRNAs in healthy individuals aged 48–52 years. This study demonstrated the potential of blood miRNA biomarkers in age prediction and provides a set of miRNA markers for developing more accurate age prediction methods.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 81-91"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577509","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 : 2025-02-28DOI: 10.1016/j.ncrna.2025.01.003
Zhi-Peng Li , Yong-Xin Mai , Shu-Ting Zhou , Chuan-jian Shi , Jiang Shao , Pu-ping Liang , Wei-cheng Liang , Jin-fang Zhang
Objective
Recent evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating bone remodeling and skeletal homeostasis by harmonizing osteoblast and osteoclast development. Notably, the oncogenic lncRNA, Hottip, implicated in osteogenesis regulation, remains insufficiently elucidated. This study aims to delineate Hottip's role in bone remodeling and skeletal homeostasis.
Methods
Hottip knockout mice were generated to discern its impact on bone metabolism. In vitro experiments probed cellular mechanisms influenced by Hottip, while molecular interactions were explored to understand its basis. The therapeutic potential of Hottip overexpression was investigated through in vivo experiments.
Results
Hottip knockout mice displayed disrupted bone metabolism, aberrant tissue, and compromised quality, leading to delayed fracture healing. In vitro, Hottip knockdown impeded osteoblast differentiation, while promoting osteoclast differentiation, with converse effects upon Hottip overexpression. Mechanistically, Hottip physically interacted with EZH2, inducing its degradation and enhancing osteogenic gene transcription by suppressing H3K9me3 and H3K27me3. In vivo experiments validated Hottip overexpression's potential to promote bone regeneration and hasten fracture healing.
Conclusion
In summary, this study identifies Hottip as a critical regulator in osteoblast and osteoclast differentiation, crucial for maintaining skeletal homeostasis. Hottip emerges as a promising therapeutic target for enhancing bone regeneration. These findings contribute valuable insights into lncRNA-mediated mechanisms governing skeletal dynamics.
{"title":"Long noncoding RNA hottip maintained skeletal homeostasis via suppressing the enhancer of zeste homolog 2 (Ezh2)/histone methylation regulatory axis","authors":"Zhi-Peng Li , Yong-Xin Mai , Shu-Ting Zhou , Chuan-jian Shi , Jiang Shao , Pu-ping Liang , Wei-cheng Liang , Jin-fang Zhang","doi":"10.1016/j.ncrna.2025.01.003","DOIUrl":"10.1016/j.ncrna.2025.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>Recent evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating bone remodeling and skeletal homeostasis by harmonizing osteoblast and osteoclast development. Notably, the oncogenic lncRNA, Hottip, implicated in osteogenesis regulation, remains insufficiently elucidated. This study aims to delineate Hottip's role in bone remodeling and skeletal homeostasis.</div></div><div><h3>Methods</h3><div>Hottip knockout mice were generated to discern its impact on bone metabolism. <em>In vitro</em> experiments probed cellular mechanisms influenced by Hottip, while molecular interactions were explored to understand its basis. The therapeutic potential of Hottip overexpression was investigated through <em>in vivo</em> experiments.</div></div><div><h3>Results</h3><div>Hottip knockout mice displayed disrupted bone metabolism, aberrant tissue, and compromised quality, leading to delayed fracture healing. <em>In vitro</em>, Hottip knockdown impeded osteoblast differentiation, while promoting osteoclast differentiation, with converse effects upon Hottip overexpression. Mechanistically, Hottip physically interacted with EZH2, inducing its degradation and enhancing osteogenic gene transcription by suppressing H3K9me3 and H3K27me3. <em>In vivo</em> experiments validated Hottip overexpression's potential to promote bone regeneration and hasten fracture healing.</div></div><div><h3>Conclusion</h3><div>In summary, this study identifies Hottip as a critical regulator in osteoblast and osteoclast differentiation, crucial for maintaining skeletal homeostasis. Hottip emerges as a promising therapeutic target for enhancing bone regeneration. These findings contribute valuable insights into lncRNA-mediated mechanisms governing skeletal dynamics<strong>.</strong></div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 141-151"},"PeriodicalIF":5.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704047","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}
MicroRNAs (miRNAs) are small non-coding RNAs that act as critical regulators of gene expression by repressing mRNA translation. The role of miRNAs in cell physiology spans from cell cycle control to cell proliferation and differentiation, both during development and in adult tissues. Accordingly, dysregulated expression of miRNAs has been reported in several diseases, including cancer, where miRNAs can act as oncogenes or oncosuppressors. Of note, miRNA signatures are also under investigation for classification, diagnosis, and prognosis of cancer patients.
Brain tumours are primarily associated with poor prognosis and high mortality, highlighting an urgent need for novel diagnostic, prognostic, and therapeutic tools. Among miRNAs investigated in brain tumours, miR-326 has been shown to act as a tumour suppressor in adult and paediatric brain cancers. In this review, we describe the role of miR-326 in malignant as well as benign cancers originating from brain tissue. In addition, since miR-326 expression can be regulated by other non-coding RNA species, adding a further layer of regulation in the cancer-promoting axis, we discuss this miRNA's role in targeted therapy for brain cancers.
{"title":"MiR-326: Role and significance in brain cancers","authors":"Zaira Spinello , Zein Mersini Besharat , Fabrizio Mainiero , Aurelia Rughetti , Laura Masuelli , Elisabetta Ferretti , Giuseppina Catanzaro","doi":"10.1016/j.ncrna.2025.02.006","DOIUrl":"10.1016/j.ncrna.2025.02.006","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are small non-coding RNAs that act as critical regulators of gene expression by repressing mRNA translation. The role of miRNAs in cell physiology spans from cell cycle control to cell proliferation and differentiation, both during development and in adult tissues. Accordingly, dysregulated expression of miRNAs has been reported in several diseases, including cancer, where miRNAs can act as oncogenes or oncosuppressors. Of note, miRNA signatures are also under investigation for classification, diagnosis, and prognosis of cancer patients.</div><div>Brain tumours are primarily associated with poor prognosis and high mortality, highlighting an urgent need for novel diagnostic, prognostic, and therapeutic tools. Among miRNAs investigated in brain tumours, miR-326 has been shown to act as a tumour suppressor in adult and paediatric brain cancers. In this review, we describe the role of miR-326 in malignant as well as benign cancers originating from brain tissue. In addition, since miR-326 expression can be regulated by other non-coding RNA species, adding a further layer of regulation in the cancer-promoting axis, we discuss this miRNA's role in targeted therapy for brain cancers.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 56-64"},"PeriodicalIF":5.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528734","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}
Matrix metalloproteinases (MMPs) cleave proteins of extracellular matrix thus facilitating cellular invasion and cancer progression. High MMP-2 activity is frequently reported in several diseases including endometriosis and cancer. Endometriosis, though benign causing pain and infertility, rarely culminate into ovarian cancer. New diagnostic markers are needed for early diagnosis and proper therapeutic avenues since the only diagnostic method is laparoscopy to date. Emerging evidence shows the importance of MMP activity and involvement of noncoding RNA, e.g. miRNA thereon. We investigated the role of miRNA-34a in MMP-2-mediated regulation of invasion and tumorigenesis in endometriosis. Database analysis showed a decreased miRNA-34a in different gynecological malignancies. qRT-PCR with human endometriotic and control tissues revealed a significant elevation in MMP-2 activity with downregulated miR-34a in diseased individuals proving an inverse correlation between miRNA-34a and MMP-2. Luciferase assay in SK-OV-3 cells demonstrated that miRNA-34a-5p directly binds the 3′UTR of the MMP-2 promoter to reduce its transcription followed by suppression of invasion. The zymographic assay also showed a reduced MMP-2 activity upon miR-34a treatment in End1/E6E7 and SK-OV-3 cells. We also found that miRNA-34a-5p inhibits invasion, migration, colony/spheroid formation, and stemness of the cells thereby reducing in vitro tumorigenesis. Subsequently, the immunoblotting results confirmed that MMP-2, and mesenchymal markers like n-cadherin, vimentin, and slug expression were downregulated, whereas the e-cadherin was upregulated in the cells treated with miRNA-34a mimic. Our study demonstrates the direct binding of miR-34a-5p with the MMP-2 gene's 3′UTR and thus repressed its transcription as well as suppressing endometriosis progression.
{"title":"Suppression of endometriosis by miRNA-34a via inhibition of matrix metalloproteinase-2: An alternative pathway to impede invasion","authors":"Yasmin Begum , Anuradha Pandit , Devendra Shukla , Rahul Gupta , Pramathes DasMahapatra , Amit Kumar Srivastava , Snehasikta Swarnakar","doi":"10.1016/j.ncrna.2025.02.001","DOIUrl":"10.1016/j.ncrna.2025.02.001","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs) cleave proteins of extracellular matrix thus facilitating cellular invasion and cancer progression. High MMP-2 activity is frequently reported in several diseases including endometriosis and cancer. Endometriosis, though benign causing pain and infertility, rarely culminate into ovarian cancer. New diagnostic markers are needed for early diagnosis and proper therapeutic avenues since the only diagnostic method is laparoscopy to date. Emerging evidence shows the importance of MMP activity and involvement of noncoding RNA, e.g. miRNA thereon. We investigated the role of miRNA-34a in MMP-2-mediated regulation of invasion and tumorigenesis in endometriosis. Database analysis showed a decreased miRNA-34a in different gynecological malignancies. qRT-PCR with human endometriotic and control tissues revealed a significant elevation in MMP-2 activity with downregulated miR-34a in diseased individuals proving an inverse correlation between miRNA-34a and MMP-2. Luciferase assay in SK-OV-3 cells demonstrated that miRNA-34a-5p directly binds the 3′UTR of the MMP-2 promoter to reduce its transcription followed by suppression of invasion. The zymographic assay also showed a reduced MMP-2 activity upon miR-34a treatment in End1/E6E7 and SK-OV-3 cells. We also found that miRNA-34a-5p inhibits invasion, migration, colony/spheroid formation, and stemness of the cells thereby reducing in vitro tumorigenesis. Subsequently, the immunoblotting results confirmed that MMP-2, and mesenchymal markers like n-cadherin, vimentin, and slug expression were downregulated, whereas the e-cadherin was upregulated in the cells treated with miRNA-34a mimic. Our study demonstrates the direct binding of miR-34a-5p with the MMP-2 gene's 3′UTR and thus repressed its transcription as well as suppressing endometriosis progression.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"12 ","pages":"Pages 92-101"},"PeriodicalIF":5.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592783","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 : 2025-02-22DOI: 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}
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