Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic.
乳腺癌(BC)是全球最常见的癌症类型之一,其发病机制复杂,亚型分类也同样复杂。微小 RNA(miRNA 或 miR)是一种非编码 RNA 小分子,在基因表达中起着至关重要的作用,与不同类型癌症中的肿瘤发生和血管生成有着重要联系。最近,人们阐明了编码和非编码 RNA 之间复杂的相互作用,进一步揭示了这些分子在癌症形成过程中所起作用的复杂性。在此背景下,人们对 miR 在 BC 中作用的认识有了显著提高,强调了这些分子的失调是影响 BC 发生、发展和分类的额外因素。在过去几年中,发表了大量有关 miR-125 在人类病理学,特别是在几种癌症形成中的作用的论文。有趣的是,miR-125 家族成员最近也与 BC 的形成有关,而且该分子与靶 mRNA 之间复杂的相互作用(竞争性内源性 RNA 网络,或 ceRNET)也已被描述。在这篇综述中,我们将总结有关这一主题的最新研究进展。
{"title":"miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine.","authors":"Roberto Piergentili, Enrico Marinelli, Gaspare Cucinella, Alessandra Lopez, Gabriele Napoletano, Giuseppe Gullo, Simona Zaami","doi":"10.3390/ncrna10020016","DOIUrl":"10.3390/ncrna10020016","url":null,"abstract":"<p><p>Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"10 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samar A Zailaie, Basmah B Khoja, Jumana J Siddiqui, Mohammad H Mawardi, Emily Heaphy, Amjad Aljagthmi, Consolato M Sergi
Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.
{"title":"Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease.","authors":"Samar A Zailaie, Basmah B Khoja, Jumana J Siddiqui, Mohammad H Mawardi, Emily Heaphy, Amjad Aljagthmi, Consolato M Sergi","doi":"10.3390/ncrna10010010","DOIUrl":"10.3390/ncrna10010010","url":null,"abstract":"<p><p>Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"10 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhenghua Chang, Rong Zhu, Jinxing Liu, Junliang Shang, Lingyun Dai
Biological research has demonstrated the significance of identifying miRNA-disease associations in the context of disease prevention, diagnosis, and treatment. However, the utilization of experimental approaches involving biological subjects to infer these associations is both costly and inefficient. Consequently, there is a pressing need to devise novel approaches that offer enhanced accuracy and effectiveness. Presently, the predominant methods employed for predicting disease associations rely on Graph Convolutional Network (GCN) techniques. However, the Graph Convolutional Network algorithm, which is locally aggregated, solely incorporates information from the immediate neighboring nodes of a given node at each layer. Consequently, GCN cannot simultaneously aggregate information from multiple nodes. This constraint significantly impacts the predictive efficacy of the model. To tackle this problem, we propose a novel approach, based on HyperGCN and Sørensen-Dice loss (HGSMDA), for predicting associations between miRNAs and diseases. In the initial phase, we developed multiple networks to represent the similarity between miRNAs and diseases and employed GCNs to extract information from diverse perspectives. Subsequently, we draw into HyperGCN to construct a miRNA-disease heteromorphic hypergraph using hypernodes and train GCN on the graph to aggregate information. Finally, we utilized the Sørensen-Dice loss function to evaluate the degree of similarity between the predicted outcomes and the ground truth values, thereby enabling the prediction of associations between miRNAs and diseases. In order to assess the soundness of our methodology, an extensive series of experiments was conducted employing the Human MicroRNA Disease Database (HMDD v3.2) as the dataset. The experimental outcomes unequivocally indicate that HGSMDA exhibits remarkable efficacy when compared to alternative methodologies. Furthermore, the predictive capacity of HGSMDA was corroborated through a case study focused on colon cancer. These findings strongly imply that HGSMDA represents a dependable and valid framework, thereby offering a novel avenue for investigating the intricate association between miRNAs and diseases.
{"title":"HGSMDA: miRNA-Disease Association Prediction Based on HyperGCN and Sørensen-Dice Loss.","authors":"Zhenghua Chang, Rong Zhu, Jinxing Liu, Junliang Shang, Lingyun Dai","doi":"10.3390/ncrna10010009","DOIUrl":"10.3390/ncrna10010009","url":null,"abstract":"<p><p>Biological research has demonstrated the significance of identifying miRNA-disease associations in the context of disease prevention, diagnosis, and treatment. However, the utilization of experimental approaches involving biological subjects to infer these associations is both costly and inefficient. Consequently, there is a pressing need to devise novel approaches that offer enhanced accuracy and effectiveness. Presently, the predominant methods employed for predicting disease associations rely on Graph Convolutional Network (GCN) techniques. However, the Graph Convolutional Network algorithm, which is locally aggregated, solely incorporates information from the immediate neighboring nodes of a given node at each layer. Consequently, GCN cannot simultaneously aggregate information from multiple nodes. This constraint significantly impacts the predictive efficacy of the model. To tackle this problem, we propose a novel approach, based on HyperGCN and Sørensen-Dice loss (HGSMDA), for predicting associations between miRNAs and diseases. In the initial phase, we developed multiple networks to represent the similarity between miRNAs and diseases and employed GCNs to extract information from diverse perspectives. Subsequently, we draw into HyperGCN to construct a miRNA-disease heteromorphic hypergraph using hypernodes and train GCN on the graph to aggregate information. Finally, we utilized the Sørensen-Dice loss function to evaluate the degree of similarity between the predicted outcomes and the ground truth values, thereby enabling the prediction of associations between miRNAs and diseases. In order to assess the soundness of our methodology, an extensive series of experiments was conducted employing the Human MicroRNA Disease Database (HMDD v3.2) as the dataset. The experimental outcomes unequivocally indicate that HGSMDA exhibits remarkable efficacy when compared to alternative methodologies. Furthermore, the predictive capacity of HGSMDA was corroborated through a case study focused on colon cancer. These findings strongly imply that HGSMDA represents a dependable and valid framework, thereby offering a novel avenue for investigating the intricate association between miRNAs and diseases.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"10 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10893088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rana A Youness, Danira Ashraf Habashy, Nour Khater, Kareem Elsayed, Alyaa Dawoud, Sousanna Hakim, Heba Nafea, Carole Bourquin, Reham M Abdel-Kader, Mohamed Z Gad
Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a "Maestro" role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H2S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H2S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders.
{"title":"Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review.","authors":"Rana A Youness, Danira Ashraf Habashy, Nour Khater, Kareem Elsayed, Alyaa Dawoud, Sousanna Hakim, Heba Nafea, Carole Bourquin, Reham M Abdel-Kader, Mohamed Z Gad","doi":"10.3390/ncrna10010007","DOIUrl":"10.3390/ncrna10010007","url":null,"abstract":"<p><p>Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a \"Maestro\" role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H<sub>2</sub>S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H<sub>2</sub>S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H<sub>2</sub>S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H<sub>2</sub>S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"10 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The analysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that hold potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods.
{"title":"sRNAflow: A Tool for the Analysis of Small RNA-Seq Data.","authors":"Pawel Zayakin","doi":"10.3390/ncrna10010006","DOIUrl":"10.3390/ncrna10010006","url":null,"abstract":"<p><p>The analysis of small RNA sequencing data across a range of biofluids is a significant research area, given the diversity of RNA types that hold potential diagnostic, prognostic, and predictive value. The intricate task of segregating the complex mixture of small RNAs from both human and other species, including bacteria, fungi, and viruses, poses one of the most formidable challenges in the analysis of small RNA sequencing data, currently lacking satisfactory solutions. This study introduces sRNAflow, a user-friendly bioinformatic tool with a web interface designed for the analysis of small RNAs obtained from biological fluids. Tailored to the unique requirements of such samples, the proposed pipeline addresses various challenges, including filtering potential RNAs from reagents and environment, classifying small RNA types, managing small RNA annotation overlap, conducting differential expression assays, analysing isomiRs, and presenting an approach to identify the sources of small RNAs within samples. sRNAflow also encompasses an alternative alignment-free analysis of RNA-seq data, featuring clustering and initial RNA source identification using BLAST. This comprehensive approach facilitates meaningful comparisons of results between different analytical methods.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"10 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco Rios, Maritere Uriostegui-Arcos, Mario Zurita
A characteristic of the cellular response to stress is the production of RNAs generated from a readthrough transcription of genes, called downstream-of-gene-(DoG)-containing transcripts. Additionally, transcription inhibitor drugs are candidates for fighting cancer. In this work, we report the results of a bioinformatic analysis showing that one of the responses to transcription inhibition is the generation of DoGs in cancer cells. Although some genes that form DoGs were shared between the two cancer lines, there did not appear to be a functional correlation between them. However, our findings show that DoGs are generated as part of the cellular response to transcription inhibition like other types of cellular stress, suggesting that they may be part of the defense against transcriptional stress.
{"title":"Transcriptional Stress Induces the Generation of DoGs in Cancer Cells.","authors":"Francisco Rios, Maritere Uriostegui-Arcos, Mario Zurita","doi":"10.3390/ncrna10010005","DOIUrl":"10.3390/ncrna10010005","url":null,"abstract":"<p><p>A characteristic of the cellular response to stress is the production of RNAs generated from a readthrough transcription of genes, called downstream-of-gene-(DoG)-containing transcripts. Additionally, transcription inhibitor drugs are candidates for fighting cancer. In this work, we report the results of a bioinformatic analysis showing that one of the responses to transcription inhibition is the generation of DoGs in cancer cells. Although some genes that form DoGs were shared between the two cancer lines, there did not appear to be a functional correlation between them. However, our findings show that DoGs are generated as part of the cellular response to transcription inhibition like other types of cellular stress, suggesting that they may be part of the defense against transcriptional stress.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"10 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Cataldo, Douglas G. Cheung, John Hagan, Matteo Fassan, Sukhinder Sandhu-Deol, Carlo M. Croce, Gianpiero di Leva, M. Iorio
MiRNAs play crucial roles in a broad spectrum of biological processes, both physiological and pathological. Different reports implicate miR-205 in the control of breast stem cell properties. Differential miR-205 expression has been observed in different stages of mammary gland development and maturation. However, a functional role in this process has not been clearly demonstrated. We generated an miR-205 knockout in the FVB/N mouse strain, which is viable and characterized by enhanced mammary gland development. Indeed, mammary glands of miR-205 −/− female mice at different ages (1.5 and 5.5 months) show increased outgrowth and branching. This evidence is consistent with our previously reported data demonstrating the direct miR-205-mediated targeting of HER3, a master regulator of mammary gland development, and the oncosuppressive activity of this microRNA in different types of breast cancer.
{"title":"Genetic Loss of miR-205 Causes Increased Mammary Gland Development","authors":"A. Cataldo, Douglas G. Cheung, John Hagan, Matteo Fassan, Sukhinder Sandhu-Deol, Carlo M. Croce, Gianpiero di Leva, M. Iorio","doi":"10.3390/ncrna10010004","DOIUrl":"https://doi.org/10.3390/ncrna10010004","url":null,"abstract":"MiRNAs play crucial roles in a broad spectrum of biological processes, both physiological and pathological. Different reports implicate miR-205 in the control of breast stem cell properties. Differential miR-205 expression has been observed in different stages of mammary gland development and maturation. However, a functional role in this process has not been clearly demonstrated. We generated an miR-205 knockout in the FVB/N mouse strain, which is viable and characterized by enhanced mammary gland development. Indeed, mammary glands of miR-205 −/− female mice at different ages (1.5 and 5.5 months) show increased outgrowth and branching. This evidence is consistent with our previously reported data demonstrating the direct miR-205-mediated targeting of HER3, a master regulator of mammary gland development, and the oncosuppressive activity of this microRNA in different types of breast cancer.","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"76 24","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139130634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart failure (HF) is a widespread cardiovascular condition that poses significant risks to a wide spectrum of age groups and leads to terminal illness. Although our understanding of the underlying mechanisms of HF has improved, the available treatments still remain inadequate. Recently, long non-coding RNAs (lncRNAs) have emerged as crucial players in cardiac function, showing possibilities as potential targets for HF therapy. These versatile molecules interact with chromatin, proteins, RNA, and DNA, influencing gene regulation. Notable lncRNAs like Fendrr, Trpm3, and Scarb2 have demonstrated therapeutic potential in HF cases. Additionally, utilizing lncRNAs to forecast survival rates in HF patients and distinguish various cardiac remodeling conditions holds great promise, offering significant benefits in managing cardiovascular disease and addressing its far-reaching societal and economic impacts. This underscores the pivotal role of lncRNAs in the context of HF research and treatment.
{"title":"Long Non-Coding RNAs (lncRNAs) in Heart Failure: A Comprehensive Review","authors":"Shambhavi Jha, Vasanth Kanth Thasma Loganathbabu, Kasinathan Kumaran, Gopinath Krishnasamy, Kandasamy Nagarajan Aruljothi","doi":"10.3390/ncrna10010003","DOIUrl":"https://doi.org/10.3390/ncrna10010003","url":null,"abstract":"Heart failure (HF) is a widespread cardiovascular condition that poses significant risks to a wide spectrum of age groups and leads to terminal illness. Although our understanding of the underlying mechanisms of HF has improved, the available treatments still remain inadequate. Recently, long non-coding RNAs (lncRNAs) have emerged as crucial players in cardiac function, showing possibilities as potential targets for HF therapy. These versatile molecules interact with chromatin, proteins, RNA, and DNA, influencing gene regulation. Notable lncRNAs like Fendrr, Trpm3, and Scarb2 have demonstrated therapeutic potential in HF cases. Additionally, utilizing lncRNAs to forecast survival rates in HF patients and distinguish various cardiac remodeling conditions holds great promise, offering significant benefits in managing cardiovascular disease and addressing its far-reaching societal and economic impacts. This underscores the pivotal role of lncRNAs in the context of HF research and treatment.","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"26 34","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139148072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina Jonas, Felix Prinz, Manuela Ferracin, Katarina Krajina, Alexander Deutsch, Tobias Madl, B. Rinner, O. Slaby, Christiane Klec, Martin Pichler
MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC.
{"title":"MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B","authors":"Katharina Jonas, Felix Prinz, Manuela Ferracin, Katarina Krajina, Alexander Deutsch, Tobias Madl, B. Rinner, O. Slaby, Christiane Klec, Martin Pichler","doi":"10.3390/ncrna10010002","DOIUrl":"https://doi.org/10.3390/ncrna10010002","url":null,"abstract":"MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC.","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"26 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A growing body of literature connects HSCR to alterations in miRNA expression, but there are limited data on the normal miRNA landscape in the developing ENS. We sequenced small RNAs (smRNA-seq) and messenger RNAs (mRNA-seq) from ENS precursor cells of mid-gestation Ednrb-EGFP mice and compared them to aggregated RNA from all other cells in the developing bowel. Our smRNA-seq results identified 73 miRNAs that were significantly enriched and highly expressed in the developing ENS, with miR-9, miR-27b, miR-124, miR-137, and miR-488 as our top 5 miRNAs that are conserved in humans. However, contrary to prior reports, our follow-up analyses of miR-137 showed that loss of Mir137 in Nestin-cre, Wnt1-cre, Sox10-cre, or Baf53b-cre lineage cells had no effect on mouse survival or ENS development. Our data provide important context for future studies of miRNAs in HSCR and other ENS diseases and highlight open questions about facility-specific factors in development.
{"title":"Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System","authors":"Christopher Pai, Rajarshi Sengupta, R. Heuckeroth","doi":"10.3390/ncrna10010001","DOIUrl":"https://doi.org/10.3390/ncrna10010001","url":null,"abstract":"The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A growing body of literature connects HSCR to alterations in miRNA expression, but there are limited data on the normal miRNA landscape in the developing ENS. We sequenced small RNAs (smRNA-seq) and messenger RNAs (mRNA-seq) from ENS precursor cells of mid-gestation Ednrb-EGFP mice and compared them to aggregated RNA from all other cells in the developing bowel. Our smRNA-seq results identified 73 miRNAs that were significantly enriched and highly expressed in the developing ENS, with miR-9, miR-27b, miR-124, miR-137, and miR-488 as our top 5 miRNAs that are conserved in humans. However, contrary to prior reports, our follow-up analyses of miR-137 showed that loss of Mir137 in Nestin-cre, Wnt1-cre, Sox10-cre, or Baf53b-cre lineage cells had no effect on mouse survival or ENS development. Our data provide important context for future studies of miRNAs in HSCR and other ENS diseases and highlight open questions about facility-specific factors in development.","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"53 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139164178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}