Pub Date : 2024-11-09DOI: 10.1016/j.ncrna.2024.10.008
Hongjiao Wu , Yuning Xie , Ang Li , Xiyao Liu , Liwen Guo , Fengjun Wu , Zhenbang Yang , Zhi Zhang , Xuemei Zhang
Lung cancer is primarily classified as NSCLC, which is distinguished by a wide range of genetic variations. This study focused on RNF144A-AS1, a relatively unexplored lncRNA, to explore the impact of its genetic polymorphisms on the susceptibility to NSCLC. We detected RNF144A-AS1 expression and its correlation with prognosis and clinical pathological features using bioinformatics analysis. The association between RNF144A-AS1 polymorphism and NSCLC susceptibility was evaluated using case-control methods. This investigation featured a cohort of 700 NSCLC individuals and 700 healthy controls. The genotype of genetic variation was detected by PCR-RFLP and iMLDR, followed by subsequent calculation of OR and 95 % CI. Our data show that RNF144A-AS1 exhibits high expression levels in LUAD tissues and its expression is closely linked to LUAD progression and prognosis. Carrier of RNF144A-AS1 rs3806609 TT genotype increased NSCLC susceptibility compared to carrier of rs3806609 CC genotype (OR = 2.21, 95%CI = 1.57–3.13). Our study identifies RNF144A-AS1 genetic variants as potential susceptibility markers in NSCLC. RNF144A-AS1 promotes cell proliferation and migration in LUAD through the IFN-γ/JAK2/STAT1 signalling pathway. Collectively, these findings pave the way for developing targeted therapies and diagnostic tools based on RNF144A-AS1 and its variants.
{"title":"LncRNA RNF144A-AS1 gene polymorphisms and their influence on lung cancer patients in the Chinese Han population","authors":"Hongjiao Wu , Yuning Xie , Ang Li , Xiyao Liu , Liwen Guo , Fengjun Wu , Zhenbang Yang , Zhi Zhang , Xuemei Zhang","doi":"10.1016/j.ncrna.2024.10.008","DOIUrl":"10.1016/j.ncrna.2024.10.008","url":null,"abstract":"<div><div>Lung cancer is primarily classified as NSCLC, which is distinguished by a wide range of genetic variations. This study focused on <em>RNF144A-AS1</em>, a relatively unexplored lncRNA, to explore the impact of its genetic polymorphisms on the susceptibility to NSCLC. We detected <em>RNF144A-AS1</em> expression and its correlation with prognosis and clinical pathological features using bioinformatics analysis. The association between <em>RNF144A-AS1</em> polymorphism and NSCLC susceptibility was evaluated using case-control methods. This investigation featured a cohort of 700 NSCLC individuals and 700 healthy controls. The genotype of genetic variation was detected by PCR-RFLP and iMLDR, followed by subsequent calculation of <em>OR</em> and 95 % <em>CI</em>. Our data show that <em>RNF144A-AS1</em> exhibits high expression levels in LUAD tissues and its expression is closely linked to LUAD progression and prognosis. Carrier of <em>RNF144A-AS1</em> rs3806609 TT genotype increased NSCLC susceptibility compared to carrier of rs3806609 CC genotype (<em>OR</em> = 2.21, 95%<em>CI</em> = 1.57–3.13). Our study identifies <em>RNF144A-AS1</em> genetic variants as potential susceptibility markers in NSCLC. <em>RNF144A-AS1</em> promotes cell proliferation and migration in LUAD through the IFN-γ/JAK2/STAT1 signalling pathway. Collectively, these findings pave the way for developing targeted therapies and diagnostic tools based on <em>RNF144A-AS1</em> and its variants.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 252-260"},"PeriodicalIF":5.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661440","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}
Long non-coding RNAs (lncRNAs) can be incorporated into exosomes to mediate the intercellular communication, regulating the occurrence, development, and immunosuppression of cancers. T cell dysfunction has been a hallmark of many cancers, including melanoma, which enables cancer cells escape from host immune surveillance. However, the molecular mechanism of exosome-transmitted lncRNAs in CD8+ T cell dysfunction in melanoma remains largely unclear.
Method
The expression of circulating LINC01214 (cirLINC01214) was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Exosomes were isolation from the culture medium and plasma of melanoma patients via ultracentrifugation and characterized by transmission electronic microscopy. The regulation of exosomal LINC01214 on CD8+ T cell function was determined by ELISA. The molecular mechanism of exosomal LINC01214 in CD8+ T cells were assessed by the RNA immunoprecipitation and pull-down assay. A mouse model with reconstituted human immune system was used to explore the role of exosomal LINC01214 in the resistance to anti-PD1 therapy.
Results
LINC01214 was highly expressed in melanoma tissues compared with matched adjacent normal tissues. Increased levels of circulating LINC01214 (cirLINC01214) was observed in melanoma patient plasma and correlated with poor PD-1 immunotherapy response. The cirLINC01214 was predominantly released by melanoma cells in an exosome manner. Melanoma cell-derived exosomal LINC01214 inhibits the production of IFN-γ, TNF-α, Granzyme-B and Perforin by CD8+ T cells. Further mechanism study found that cirLINC01214 delivered by exosomes suppressed CD8+ T cell function by up-regulating the expression of Protein Phosphatase 1 Regulatory Inhibitor Subunit 11 (PPP1R11) through sponging miR-4492. CirLINC01214 conferred resistance to PD-1 immunotherapy in melanoma xenograft mouse model. Melanoma patients with poor prognosis after PD-1 treatment carried high levels of exosomal LINC01214. Additionally, the secretion of exosomal cirLINC01214 was enhanced by the Warburg effect, which was consistent with the reprogrammed glucose metabolism of melanoma.
Conclusions
Our results demonstrated that exosomal LINC01214 released by melanoma cells promoted immunotherapy resistance by inducing CD8+ T cell dysfunction via the miR-4492/PPP1R11 regulatory loop. Targeting cirLINC01214 might be a potential therapeutic strategy to enhance the outcome of immunotherapy in melanoma.
{"title":"Glycolysis regulated exosomal LINC01214 inhibited CD8+ T cell function and induced anti-PD1 resistance in melanoma via modulating miR-4492/PPP1R11 axis","authors":"Zhi Ding, Baojin Wu, Junyi Yang, Daohe Wang, Jing Qiao, Fanli Guo","doi":"10.1016/j.ncrna.2024.10.005","DOIUrl":"10.1016/j.ncrna.2024.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Long non-coding RNAs (lncRNAs) can be incorporated into exosomes to mediate the intercellular communication, regulating the occurrence, development, and immunosuppression of cancers. T cell dysfunction has been a hallmark of many cancers, including melanoma, which enables cancer cells escape from host immune surveillance. However, the molecular mechanism of exosome-transmitted lncRNAs in CD8<sup>+</sup> T cell dysfunction in melanoma remains largely unclear.</div></div><div><h3>Method</h3><div>The expression of circulating LINC01214 (cirLINC01214) was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Exosomes were isolation from the culture medium and plasma of melanoma patients via ultracentrifugation and characterized by transmission electronic microscopy. The regulation of exosomal LINC01214 on CD8<sup>+</sup> T cell function was determined by ELISA. The molecular mechanism of exosomal LINC01214 in CD8<sup>+</sup> T cells were assessed by the RNA immunoprecipitation and pull-down assay. A mouse model with reconstituted human immune system was used to explore the role of exosomal LINC01214 in the resistance to anti-PD1 therapy.</div></div><div><h3>Results</h3><div>LINC01214 was highly expressed in melanoma tissues compared with matched adjacent normal tissues. Increased levels of circulating LINC01214 (cirLINC01214) was observed in melanoma patient plasma and correlated with poor PD-1 immunotherapy response. The cirLINC01214 was predominantly released by melanoma cells in an exosome manner. Melanoma cell-derived exosomal LINC01214 inhibits the production of IFN-γ, TNF-α, Granzyme-B and Perforin by CD8<sup>+</sup> T cells. Further mechanism study found that cirLINC01214 delivered by exosomes suppressed CD8<sup>+</sup> T cell function by up-regulating the expression of Protein Phosphatase 1 Regulatory Inhibitor Subunit 11 (PPP1R11) through sponging miR-4492. CirLINC01214 conferred resistance to PD-1 immunotherapy in melanoma xenograft mouse model. Melanoma patients with poor prognosis after PD-1 treatment carried high levels of exosomal LINC01214. Additionally, the secretion of exosomal cirLINC01214 was enhanced by the Warburg effect, which was consistent with the reprogrammed glucose metabolism of melanoma.</div></div><div><h3>Conclusions</h3><div>Our results demonstrated that exosomal LINC01214 released by melanoma cells promoted immunotherapy resistance by inducing CD8<sup>+</sup> T cell dysfunction via the miR-4492/PPP1R11 regulatory loop. Targeting cirLINC01214 might be a potential therapeutic strategy to enhance the outcome of immunotherapy in melanoma.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 242-251"},"PeriodicalIF":5.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593531","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 : 2024-10-28DOI: 10.1016/j.ncrna.2024.10.006
Anna Lucia Tornesello , Andrea Cerasuolo , Noemy Starita , Sara Amiranda , Tiziana Pecchillo Cimmino , Patrizia Bonelli , Franca Maria Tuccillo , Franco Maria Buonaguro , Luigi Buonaguro , Maria Lina Tornesello
Non-coding RNAs have long been recognized for their regulatory roles in various cellular processes, including cancer development and progression. Recent advancements have shed light on a novel aspect of non-coding RNA biology, revealing their ability to encode endogenous peptides also named micropeptides or microprotein through short open reading frames (sORFs). These small proteins play crucial roles in oncogenic processes, acting as either tumour suppressors or tumour promoters, and hold enormous potential as biomarkers for early diagnosis of cancer and as therapeutic targets. This comprehensive review highlights the state of the art on peptides encoded by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), elucidating their regulatory functions and implications in different cancer types, including breast cancer, hepatocellular carcinoma and colorectal cancer. The review also discusses challenges and future directions in the exploration of these emerging players in cancer biology, emphasizing the importance of further investigation for their clinical translation in diagnosis and therapy.
{"title":"Emerging role of endogenous peptides encoded by non-coding RNAs in cancer biology","authors":"Anna Lucia Tornesello , Andrea Cerasuolo , Noemy Starita , Sara Amiranda , Tiziana Pecchillo Cimmino , Patrizia Bonelli , Franca Maria Tuccillo , Franco Maria Buonaguro , Luigi Buonaguro , Maria Lina Tornesello","doi":"10.1016/j.ncrna.2024.10.006","DOIUrl":"10.1016/j.ncrna.2024.10.006","url":null,"abstract":"<div><div>Non-coding RNAs have long been recognized for their regulatory roles in various cellular processes, including cancer development and progression. Recent advancements have shed light on a novel aspect of non-coding RNA biology, revealing their ability to encode endogenous peptides also named micropeptides or microprotein through short open reading frames (sORFs). These small proteins play crucial roles in oncogenic processes, acting as either tumour suppressors or tumour promoters, and hold enormous potential as biomarkers for early diagnosis of cancer and as therapeutic targets. This comprehensive review highlights the state of the art on peptides encoded by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), elucidating their regulatory functions and implications in different cancer types, including breast cancer, hepatocellular carcinoma and colorectal cancer. The review also discusses challenges and future directions in the exploration of these emerging players in cancer biology, emphasizing the importance of further investigation for their clinical translation in diagnosis and therapy.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 231-241"},"PeriodicalIF":5.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572130","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}
Transfer RNA-derived small RNAs (tsRNAs) are a newly recognized class of small non-coding RNAs that are implicated in a variety of cancers, including head and neck tumors. Studies have identified tsRNAs with differential expression profiles in head and neck malignancies, highlighting their potential as biomarkers for diagnosis and prognosis. Functional analyses show that tsRNAs are involved in regulating critical cellular pathways, including those related to cell proliferation, migration, and metabolic processes. Despite these encouraging insights, there are myriad challenges that must be tackled. In summary, tsRNAs present considerable potential as therapeutic targets and biomarkers in the realm of head and neck tumors, meriting further investigation and clinical application to optimize outcomes in the management of these complex diseases. This literature review synthesizes current research on tsRNAs, tsRNAs hold significant promise as biomarkers and therapeutic targets, with the potential to transform diagnostic and treatment strategies for head and neck tumors, ultimately improving patient outcomes.
{"title":"tsRNA in head and neck tumors: Opportunities and challenges in the field","authors":"Zhuo wu , Yufeng Xu , Changzeng Zhou , Yongbo Zhang , Jingjing Chen","doi":"10.1016/j.ncrna.2024.10.003","DOIUrl":"10.1016/j.ncrna.2024.10.003","url":null,"abstract":"<div><div>Transfer RNA-derived small RNAs (tsRNAs) are a newly recognized class of small non-coding RNAs that are implicated in a variety of cancers, including head and neck tumors. Studies have identified tsRNAs with differential expression profiles in head and neck malignancies, highlighting their potential as biomarkers for diagnosis and prognosis. Functional analyses show that tsRNAs are involved in regulating critical cellular pathways, including those related to cell proliferation, migration, and metabolic processes. Despite these encouraging insights, there are myriad challenges that must be tackled. In summary, tsRNAs present considerable potential as therapeutic targets and biomarkers in the realm of head and neck tumors, meriting further investigation and clinical application to optimize outcomes in the management of these complex diseases. This literature review synthesizes current research on tsRNAs, tsRNAs hold significant promise as biomarkers and therapeutic targets, with the potential to transform diagnostic and treatment strategies for head and neck tumors, ultimately improving patient outcomes.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 223-230"},"PeriodicalIF":5.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444882","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 : 2024-10-11DOI: 10.1016/j.ncrna.2024.10.002
Marwa Matboli , Shaimaa Hamady , Maha Saad , Radwa Khaled , Abdelrahman Khaled , Eman MF. Barakat , Sayed Ahmed Sayed , SaraH.A. Agwa , Ibrahim Youssef
The global rise in Metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic dysfunction-associated steatohepatitis (MASH) highlights the urgent necessity for noninvasive biomarkers to detect these conditions early. To address this, we endeavored to construct a diagnostic model for MASLD/MASH using a combination of bioinformatics, molecular/biochemical data, and machine learning techniques. Initially, bioinformatics analysis was employed to identify RNA molecules associated with MASLD/MASH pathogenesis and enriched in ferroptosis and exophagy. This analysis unveiled specific networks related to ferroptosis (GPX4, LPCAT3, ACSL4, miR-4266, and LINC00442) and exophagy (TSG101, HGS, SNF8, miR-4498, miR-5189–5p, and CTBP1-AS2). Subsequently, serum samples from 400 participants (151 healthy, 150 MASH, and 99 MASLD) underwent biochemical and molecular analysis, revealing significant dyslipidemia, impaired liver function, and disrupted glycemic indicators in MASLD/MASH patients compared to healthy controls. Molecular analysis indicated increased expression of LPCAT3, ACSL4, TSG101, HGS, and SNF8, alongside decreased GPX4 levels in MASH and MASLD patients compared to controls. The expression of epigenetic regulators from both networks (miR-4498, miR-5189–5p, miR-4266, LINC00442, and CTBP1-AS2) significantly differed among the studied groups. Finally, supervised machine learning models, including Neural Networks and Random Forest, were applied to molecular signatures and clinical/biochemical data. The Random Forest model exhibited superior performance, and molecular features effectively distinguished between the three studied groups. Clinical features, particularly BMI, consistently served as discriminatory factors, while biochemical features exhibited varying discriminant behavior across MASH, MASLD, and control groups. Our study underscores the significant potential of integrating diverse data types to enable early detection of MASLD/MASH, offering a promising approach for non-invasive diagnostic strategies.
{"title":"Innovative approaches to metabolic dysfunction-associated steatohepatitis diagnosis and stratification","authors":"Marwa Matboli , Shaimaa Hamady , Maha Saad , Radwa Khaled , Abdelrahman Khaled , Eman MF. Barakat , Sayed Ahmed Sayed , SaraH.A. Agwa , Ibrahim Youssef","doi":"10.1016/j.ncrna.2024.10.002","DOIUrl":"10.1016/j.ncrna.2024.10.002","url":null,"abstract":"<div><div>The global rise in Metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic dysfunction-associated steatohepatitis (MASH) highlights the urgent necessity for noninvasive biomarkers to detect these conditions early. To address this, we endeavored to construct a diagnostic model for MASLD/MASH using a combination of bioinformatics, molecular/biochemical data, and machine learning techniques. Initially, bioinformatics analysis was employed to identify RNA molecules associated with MASLD/MASH pathogenesis and enriched in ferroptosis and exophagy. This analysis unveiled specific networks related to ferroptosis (GPX4, LPCAT3, ACSL4, miR-4266, and LINC00442) and exophagy (TSG101, HGS, SNF8, miR-4498, miR-5189–5p, and CTBP1-AS2). Subsequently, serum samples from 400 participants (151 healthy, 150 MASH, and 99 MASLD) underwent biochemical and molecular analysis, revealing significant dyslipidemia, impaired liver function, and disrupted glycemic indicators in MASLD/MASH patients compared to healthy controls. Molecular analysis indicated increased expression of LPCAT3, ACSL4, TSG101, HGS, and SNF8, alongside decreased GPX4 levels in MASH and MASLD patients compared to controls. The expression of epigenetic regulators from both networks (miR-4498, miR-5189–5p, miR-4266, LINC00442, and CTBP1-AS2) significantly differed among the studied groups. Finally, supervised machine learning models, including Neural Networks and Random Forest, were applied to molecular signatures and clinical/biochemical data. The Random Forest model exhibited superior performance, and molecular features effectively distinguished between the three studied groups. Clinical features, particularly BMI, consistently served as discriminatory factors, while biochemical features exhibited varying discriminant behavior across MASH, MASLD, and control groups. Our study underscores the significant potential of integrating diverse data types to enable early detection of MASLD/MASH, offering a promising approach for non-invasive diagnostic strategies.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 206-222"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433760","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 : 2024-10-10DOI: 10.1016/j.ncrna.2024.10.001
Liyuan Zhao , Mengyun Gu , Zhimin Sun , Lei Shi , Zixuan Yang , Minhui Zheng , Yan Wang , Luyao Sun , Gang Liu , Feng Miao , Naping Tang
Cardiovascular diseases (CVD) are widely recognized as a leading cause of death worldwide; however, early diagnosis and disease progression monitoring play a crucial role in their clinical management. The common diagnostic and prognostic biomarkers have represented a revolutionary tool for studying CVD; however, their applications are limited to invasive irreversible heart diseases, such as drug-induced myocardial injury. In light of this information, a growing number of studies are currently investigating the diagnostic and prognostic potential of novel CVD biomarkers. Examples of this are long non-coding RNA (lncRNA) and other RNAs that are specifically expressed at the early stages of heart disease. These RNAs have been reported to be involved in the development of CVD via activating or inhibiting inflammatory mediators and angiogenesis-related factors, as well as endothelial cell proliferation, migration and phenotypic transformation. This review collectively summarizes the recent studies' results concerning exosomal lncRNA biogenesis, characterization, and function, as well as its role as a novel biomarker in a variety of CVD.
{"title":"The role of exosomal lncRNAs in cardiovascular disease: Emerging insights based on molecular mechanisms and therapeutic target level","authors":"Liyuan Zhao , Mengyun Gu , Zhimin Sun , Lei Shi , Zixuan Yang , Minhui Zheng , Yan Wang , Luyao Sun , Gang Liu , Feng Miao , Naping Tang","doi":"10.1016/j.ncrna.2024.10.001","DOIUrl":"10.1016/j.ncrna.2024.10.001","url":null,"abstract":"<div><div>Cardiovascular diseases (CVD) are widely recognized as a leading cause of death worldwide; however, early diagnosis and disease progression monitoring play a crucial role in their clinical management. The common diagnostic and prognostic biomarkers have represented a revolutionary tool for studying CVD; however, their applications are limited to invasive irreversible heart diseases, such as drug-induced myocardial injury. In light of this information, a growing number of studies are currently investigating the diagnostic and prognostic potential of novel CVD biomarkers. Examples of this are long non-coding RNA (lncRNA) and other RNAs that are specifically expressed at the early stages of heart disease. These RNAs have been reported to be involved in the development of CVD via activating or inhibiting inflammatory mediators and angiogenesis-related factors, as well as endothelial cell proliferation, migration and phenotypic transformation. This review collectively summarizes the recent studies' results concerning exosomal lncRNA biogenesis, characterization, and function, as well as its role as a novel biomarker in a variety of CVD.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 198-205"},"PeriodicalIF":5.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433759","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}
Cancer cell drug resistance hinders significantly therapeutic modalities in oncology. Dacarbazine is chemotherapeutic agent traditionally used for melanoma treatment although it's effectiveness insufficient. In the present study we performed NGS-based transcriptomic profiling of B16 melanoma tumors after Dacarbazine treatment in vivo. Whole transcriptome sequencing revealed 34 differentially expressed genes most of them associated with drug resistance and apoptosis evading. In accordance to bionformatic analysis, 6 signaling cascades: “D-Amino acid metabolism”, “NF-kappa B signaling pathway”, “Phosphatidylinositol signaling system”, “P53 signaling pathway”, “IL-17 signaling pathway” and “Bile secretion” were enriched by differentially expressed genes. Next we provided a combined treatment by Dacarbazine and miR-204-5p mimic as miR-204-5p was considered previously implicated in cancer drug resistance. This approach lead to an increase of miR-204-5p expression in B16 melanoma cells in vivo that was accompanied by subsequent decrease in the expression of miR-204-5p target genes – BCL2 and SIRT1 in the primary tumors. MiR-204-5p overexpression with Dacarbazine application resulted in increased the weight, and volume of primary tumors and diminished the proportion of β-Galactosidase expression in melanoma B16-bearing mice. Taking together, our study revealed that although miR-204-5p showed antiproliferative capacities in vitro, it's mimic in combination with Dacarbazine is able to potentiate tumor growth triggering probably a switch from senescent to proliferative phenotype of malignant cells.
{"title":"MiR-204-5p overexpression abrogates Dacarbazine-induced senescence in melanoma cells in vivo MiR-204-5p abrogates senescence","authors":"Ekaterina Lapkina , Ivan Zinchenko , Viktoriya Kutcenko , Eugeniya Bondar , Andrey Kirichenko , Irina Yamskikh , Nadezhda Palkina , Tatiana Ruksha","doi":"10.1016/j.ncrna.2024.09.009","DOIUrl":"10.1016/j.ncrna.2024.09.009","url":null,"abstract":"<div><div>Cancer cell drug resistance hinders significantly therapeutic modalities in oncology. Dacarbazine is chemotherapeutic agent traditionally used for melanoma treatment although it's effectiveness insufficient. In the present study we performed NGS-based transcriptomic profiling of B16 melanoma tumors after Dacarbazine treatment in vivo. Whole transcriptome sequencing revealed 34 differentially expressed genes most of them associated with drug resistance and apoptosis evading. In accordance to bionformatic analysis, 6 signaling cascades: “D-Amino acid metabolism”, “NF-kappa B signaling pathway”, “Phosphatidylinositol signaling system”, “P53 signaling pathway”, “IL-17 signaling pathway” and “Bile secretion” were enriched by differentially expressed genes. Next we provided a combined treatment by Dacarbazine and miR-204-5p mimic as miR-204-5p was considered previously implicated in cancer drug resistance. This approach lead to an increase of miR-204-5p expression in B16 melanoma cells in vivo that was accompanied by subsequent decrease in the expression of miR-204-5p target genes – <em>BCL2</em> and <em>SIRT1</em> in the primary tumors. MiR-204-5p overexpression with Dacarbazine application resulted in increased the weight, and volume of primary tumors and diminished the proportion of β-Galactosidase expression in melanoma B16-bearing mice. Taking together, our study revealed that although miR-204-5p showed antiproliferative capacities in vitro, it's mimic in combination with Dacarbazine is able to potentiate tumor growth triggering probably a switch from senescent to proliferative phenotype of malignant cells.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 130-139"},"PeriodicalIF":5.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468054024001422/pdfft?md5=0ce9497a2cf357a1c39c78b5715a8f14&pid=1-s2.0-S2468054024001422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314205","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}
The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.
The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs.
Methods
The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients’ sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs.
Results
The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly.
Conclusions
This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.
导言：阻塞性睡眠呼吸暂停（OSA）与癌症之间的关系早已得到公认。然而，人们对睡眠呼吸暂停促进肿瘤发生的机制以及 OSA 对癌症确诊后存活率的影响知之甚少。在过去的几年中，研究的重点是探索不同的生物标志物，以了解这种关系的内在机制，而 miRNA（约 22 个核苷酸的非编码单链，转录后调控基因表达）已成为这一过程的可能参与者。研究目的是根据特定 miRNAs 的表达评估 OSA 对转移性结直肠癌（mCRC）患者生存期的影响。方法通过 qRT-PCR 分析患者血清中 6 种 miRNAs 的表达，分别是 miR-21、miR-23b、miR-26a、miR-27b、miR-145 和 miR-210。结果与无OSA的mCRC相比，有OSA的mCRC中miR-21、miR-23b、miR-26a和miR-210的表达明显上调。在有 OSA 且 miR-21、miR-23b、miR-26a 和 miR-210 表达增加的 mCRC 患者中，一线治疗后病情恶化的风险更高，总生存期和无进展生存期都明显最差。相反，随着 miR-27b 和 miR-145 表达的增加，确诊为 OSA 和 mCRC 患者的预期寿命明显改善。
{"title":"MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer","authors":"Piera Soccio , Giorgia Moriondo , Giulia Scioscia , Pasquale Tondo , Giuseppina Bruno , Guido Giordano , Roberto Sabato , Maria Pia Foschino Barbaro , Matteo Landriscina , Donato Lacedonia","doi":"10.1016/j.ncrna.2024.09.008","DOIUrl":"10.1016/j.ncrna.2024.09.008","url":null,"abstract":"<div><h3>Introduction</h3><p>The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.</p><p>The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs.</p></div><div><h3>Methods</h3><p>The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients’ sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs.</p></div><div><h3>Results</h3><p>The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly.</p></div><div><h3>Conclusions</h3><p>This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.</p></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 91-97"},"PeriodicalIF":5.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468054024001410/pdfft?md5=047b575ed7275facdb46de7373165c47&pid=1-s2.0-S2468054024001410-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232350","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}
The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.
{"title":"Emerging roles of CircRNA-miRNA networks in cancer development and therapeutic response","authors":"Mehrdad Hashemi , Elaheh Mohandesi Khosroshahi , Pouria Daneii , Aria Hassanpoor , Maedeh Eslami , Zeinab Khazaei Koohpar , Saba Asadi , Abbas Zabihi , Behdokht Jamali , Amin Ghorbani , Noushin Nabavi , Mohammad Reza Memarkashani , Shokooh Salimimoghadam , Afshin Taheriazam , Shing Cheng Tan , Maliheh Entezari , Najma Farahani , Kiavash Hushmandi","doi":"10.1016/j.ncrna.2024.09.006","DOIUrl":"10.1016/j.ncrna.2024.09.006","url":null,"abstract":"<div><p>The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.</p></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 98-115"},"PeriodicalIF":5.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468054024001392/pdfft?md5=a8d444ef2c8088ac828116ae5df5d55f&pid=1-s2.0-S2468054024001392-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243601","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 : 2024-09-10DOI: 10.1016/j.ncrna.2024.09.007
Mai A. Zaafan , Amr M. Abdelhamid
Background
Globally, myocardial infarction (MI) is one of the main causes of death. This study aims to investigate the role of miR-217 in the pathogenesis through targeting MAPK and PI3K/AKT signaling pathways in experimental model of myocardial infarction and studying the possible cardioprotective role of dihydromyricetin (DHM) through modulation of this pathway.
Methods
Dihydromyricetin was injected (100 mg/kg; p.o.) in isoprenaline induced myocardial infarction rat model for 14 days. Rats were anaesthetized and blood samples were taken for serum separation, estimation of creatine kinase-MB (CK-MB), and troponin-I levels after 24 h had passed since the last isoprenaline injection. In addition, the hearts were also used for the other biochemical studies and the histological evaluation.
Results
DHM resulted in a significant suppression of the elevated levels miR-217 and MAPK compared to the MI control group and restored the normal level of serum CK-MB. Furthermore, DHM successfully restored the oxidative balance and halted the pro-inflammatory mediators in the cardiac tissue.
Conclusion
Accordingly, our experiment emphasizes the anti-ischemic property that has been demonstrated through modulation of expression level of miR-217 and consequent deactivation of MAPK and PI3K/AKT signaling pathways, and this was assured by halting downstream pro-inflammatory markers.
{"title":"Molecular insight of miRNA-217 role in the pathogenesis of myocardial infarction: Promising diagnostic biomarker and therapeutic target","authors":"Mai A. Zaafan , Amr M. Abdelhamid","doi":"10.1016/j.ncrna.2024.09.007","DOIUrl":"10.1016/j.ncrna.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>Globally, myocardial infarction (MI) is one of the main causes of death. This study aims to investigate the role of miR-217 in the pathogenesis through targeting MAPK and PI3K/AKT signaling pathways in experimental model of myocardial infarction and studying the possible cardioprotective role of dihydromyricetin (DHM) through modulation of this pathway.</div></div><div><h3>Methods</h3><div>Dihydromyricetin was injected (100 mg/kg; p.o.) in isoprenaline induced myocardial infarction rat model for 14 days. Rats were anaesthetized and blood samples were taken for serum separation, estimation of creatine kinase-MB (CK-MB), and troponin-I levels after 24 h had passed since the last isoprenaline injection. In addition, the hearts were also used for the other biochemical studies and the histological evaluation.</div></div><div><h3>Results</h3><div>DHM resulted in a significant suppression of the elevated levels miR-217 and MAPK compared to the MI control group and restored the normal level of serum CK-MB. Furthermore, DHM successfully restored the oxidative balance and halted the pro-inflammatory mediators in the cardiac tissue.</div></div><div><h3>Conclusion</h3><div>Accordingly, our experiment emphasizes the anti-ischemic property that has been demonstrated through modulation of expression level of miR-217 and consequent deactivation of MAPK and PI3K/AKT signaling pathways, and this was assured by halting downstream pro-inflammatory markers.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"10 ","pages":"Pages 192-197"},"PeriodicalIF":5.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424486","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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