铁死亡是近年来新发现的一种程序性细胞死亡形式,以铁依赖性氧化损伤、脂质过氧化和活性氧(reactive oxygen species,ROS)积累为特征,现成为缺血再灌注损伤(ischemia and reperfusion,I/R)、心血管疾病、肿瘤和神经系统疾病领域的重要...铁死亡是近年来新发现的一种程序性细胞死亡形式,以铁依赖性氧化损伤、脂质过氧化和活性氧(reactive oxygen species,ROS)积累为特征,现成为缺血再灌注损伤(ischemia and reperfusion,I/R)、心血管疾病、肿瘤和神经系统疾病领域的重要研究课题。展开更多
Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototox...Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimall...BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimally invasive biomarkers need to be integrated into clinical practice.AIM To identify circulating microRNAs as potential CRC biomarkers through a com-parative analysis of tissue and plasma samples from patients with CRC.METHODS This case-control study conducted a quantitative real-time polymerase chain reaction analysis of 84 microRNAs in tumoral and peritumoral tissues,and 179 microRNAs in plasma from 19 patients with CRC.A control cohort for the tissue analysis and another control cohort for the plasma analysis have been enrolled.RESULTS In total,14 microRNAs were significantly differentially expressed in the tissue and plasma samples.Notably,five microRNAs(miR-26b-5p,miR-101-3p,miR-30d-5p,miR-107,and miR-21-5p)presented the same trend in terms of fold change in both types of biological samples.Significant associations between the circulating levels of miR-21-5p and miR-26b-5p and lymphovascular invasion were found.CONCLUSION These five microRNAs with significantly altered levels in plasma and tumoral tissue,could be good non-invasive CRC biomarkers candidates,enhancing screening,and supporting precision and individualized patient care.展开更多
To illustrate the mechanisms of exosomal microRNAs(miRNAs)in common mental disorders,and explore their potential as diagnostic biomarkers and therapeutic targets,a systematic literature review of relevant studies on e...To illustrate the mechanisms of exosomal microRNAs(miRNAs)in common mental disorders,and explore their potential as diagnostic biomarkers and therapeutic targets,a systematic literature review of relevant studies on exosomal miRNAs in mental disorders was conducted.Data from cell experiments,animal models,and clinical studies were analyzed and combined to study the mechanisms and roles of exosomal miRNAs in various mental disorders.Research has shown that exosomal miRNAs,such as miR-146a,miR-223,miR-125b,and miR-451a,affect Alzheimer’s disease(AD)formation by regulating key pathways such as toll-like receptor 4(TLR4)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),respectively.MiR-146a-5p regulates the occurrence of schizophrenia through the Notch pathway.TLR4 regulates miR-146a and miR-155 in major depressive disorder(MDD),and miR-144-5p regulates the disease through PI3K/Akt.Exosomal miR-484,miR-652-3p,miR-142-3p,miR-21a-3p,and miR-21-5p regulate key pathways in bipolar disorder,autism spectrum disorder,and Rett syndrome(e.g.,TLR4,PI3K/Akt,and Epha4/TEK)and have an influence on mental disorders.Exosomal miRNAs are involved in the occurrence of mental disorders through TLR4,PI3K/Akt,and Epha4/TEK pathways,which provides a clearer understanding of disease cognition.Of these pathways,the TLR4 and PI3K/Akt pathways play a role in AD,MDD,and neurodevelopmental disorders,which can be used as an effective breakthrough in the study of mental disorders.Exosomal miRNAs could also serve as diagnostic biomarkers and therapeutic targets,providing new insights into precise interventions for mental disorders.展开更多
BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the ...BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.展开更多
microRNAs (miRNAs)是一类通常存在于细胞质中的短链非编码RNAs,通过与信使RNA (mRNA)的3'非翻译区(3'untranslated region, 3'UTR)结合,发挥调节转录后基因表达的功能。miRNAs在调控多种代谢过程和信号转导途径方面起着重...microRNAs (miRNAs)是一类通常存在于细胞质中的短链非编码RNAs,通过与信使RNA (mRNA)的3'非翻译区(3'untranslated region, 3'UTR)结合,发挥调节转录后基因表达的功能。miRNAs在调控多种代谢过程和信号转导途径方面起着重要作用。线粒体是真核细胞中进行氧化代谢和ATP合成的关键场所,负责糖类、脂质和氨基酸等大分子的代谢。那些特异性定位于线粒体的miRNAs,以及在细胞质中直接或间接调节线粒体特定功能的miRNAs,被称为线粒体miRNAs (mitochondrial miRNAs, mitomiRs)。这些miRNAs能调控相关基因表达,并在关键线粒体代谢途径中发挥独特作用,从而促进肿瘤的发生与发展。本文重点探讨mitomiR在线粒体中的作用以及在肿瘤中的调控机制,旨在进一步阐明肿瘤发生发展的分子机制,开发潜在的癌症新疗法。microRNAs (miRNAs) are a class of short non-coding RNAs typically found in the cytoplasm. They function to regulate post-transcriptional gene expression by binding to the 3' untranslated region (3'UTR) of messenger RNA (mRNA). miRNAs play a crucial role in modulating various metabolic processes and signal transduction pathways. Mitochondria serve as the primary sites for oxidative metabolism and ATP synthesis in eukaryotic cells, and they are responsible for the metabolism of macromolecules, including sugars, lipids, and amino acids. Mitochondrial miRNAs (mitomiRs) are a subset of miRNAs localized specifically within mitochondria and modulate mitochondrial-specific functions, either directly or indirectly, within the cytoplasm. These mitomiRs can modulate gene expression and have a distinct role in pivotal mitochondrial metabolic pathways, thereby influencing the initiation and progression of tumors. This article concentrates on the role of mitomiRs in mitochondria and their regulatory mechanisms in tumorigenesis, with the goal of further elucidating the molecular underpinnings of tumorigenesis and development, and of identifying potential novel therapeutic targets for cancer.展开更多
BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel ...BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel of circulating microRNAs(miRNAs)independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.METHODS In the present study,we analyzed the aberrant expression of miR-21,miR-221,miR-1246,miR-145,and miR-382,in addition to the tumor biomarkers cancer antigen 15-3(CA15-3)and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in breast cancer patients with varying grades.RESULTS Our results revealed distinct expression patterns of these miRNAs between grade II and III patients.Specifically,miR-21,miR-221,and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG wereobserved in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacyin differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggestingtheir interconnected roles in breast cancer progression. Receiver operating characteristic curve analysisdemonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing thehighest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancergrades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanceddiagnostic accuracy and sensitivity.CONCLUSIONThese findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patientsbased on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting thedevelopment of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management ofbreast cancer patients.展开更多
Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,whic...Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,which is further related to successful embryo implantation or conception,either naturally or after assisted reproductive technology.Moreover,this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells(EECs),which results in altered signaling biomolecule secretion,including exosome content.In the context of endometrium regeneration,mesenchymal stromal cells(MSCs)and umbilical cord(UC)-derived stem cells have been applied in clinical trials with promising results.It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs.Specifically,microRNAs in exosomes secreted by the hypoxic damaged EECs,such as miR-214-5p and miR-21-5p,play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3(STAT3)signaling pathway.Taking into consideration the above information,UC-MSCs may be considered as a modern intervention for endometrial regeneration.展开更多
Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarke...Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.展开更多
Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with...Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.展开更多
文摘Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.
基金Supported by European Union’s NextGeneration PNRR-III-C9-2022-I5,managed by the Ministry of Research,Innovation and Digitization,No.760009/30.12.2022,code CF 14/16.11.2022Ministry of Research,Innovation and Digitization of Romania,No.PN 23.16.02.04.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimally invasive biomarkers need to be integrated into clinical practice.AIM To identify circulating microRNAs as potential CRC biomarkers through a com-parative analysis of tissue and plasma samples from patients with CRC.METHODS This case-control study conducted a quantitative real-time polymerase chain reaction analysis of 84 microRNAs in tumoral and peritumoral tissues,and 179 microRNAs in plasma from 19 patients with CRC.A control cohort for the tissue analysis and another control cohort for the plasma analysis have been enrolled.RESULTS In total,14 microRNAs were significantly differentially expressed in the tissue and plasma samples.Notably,five microRNAs(miR-26b-5p,miR-101-3p,miR-30d-5p,miR-107,and miR-21-5p)presented the same trend in terms of fold change in both types of biological samples.Significant associations between the circulating levels of miR-21-5p and miR-26b-5p and lymphovascular invasion were found.CONCLUSION These five microRNAs with significantly altered levels in plasma and tumoral tissue,could be good non-invasive CRC biomarkers candidates,enhancing screening,and supporting precision and individualized patient care.
文摘To illustrate the mechanisms of exosomal microRNAs(miRNAs)in common mental disorders,and explore their potential as diagnostic biomarkers and therapeutic targets,a systematic literature review of relevant studies on exosomal miRNAs in mental disorders was conducted.Data from cell experiments,animal models,and clinical studies were analyzed and combined to study the mechanisms and roles of exosomal miRNAs in various mental disorders.Research has shown that exosomal miRNAs,such as miR-146a,miR-223,miR-125b,and miR-451a,affect Alzheimer’s disease(AD)formation by regulating key pathways such as toll-like receptor 4(TLR4)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),respectively.MiR-146a-5p regulates the occurrence of schizophrenia through the Notch pathway.TLR4 regulates miR-146a and miR-155 in major depressive disorder(MDD),and miR-144-5p regulates the disease through PI3K/Akt.Exosomal miR-484,miR-652-3p,miR-142-3p,miR-21a-3p,and miR-21-5p regulate key pathways in bipolar disorder,autism spectrum disorder,and Rett syndrome(e.g.,TLR4,PI3K/Akt,and Epha4/TEK)and have an influence on mental disorders.Exosomal miRNAs are involved in the occurrence of mental disorders through TLR4,PI3K/Akt,and Epha4/TEK pathways,which provides a clearer understanding of disease cognition.Of these pathways,the TLR4 and PI3K/Akt pathways play a role in AD,MDD,and neurodevelopmental disorders,which can be used as an effective breakthrough in the study of mental disorders.Exosomal miRNAs could also serve as diagnostic biomarkers and therapeutic targets,providing new insights into precise interventions for mental disorders.
基金Supported by Patronage of the Autonomous University of Nayarit,Quality Postgraduate Program with resources from the 15%Special Tax allocated to the UAN 2022.
文摘BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.
文摘microRNAs (miRNAs)是一类通常存在于细胞质中的短链非编码RNAs,通过与信使RNA (mRNA)的3'非翻译区(3'untranslated region, 3'UTR)结合,发挥调节转录后基因表达的功能。miRNAs在调控多种代谢过程和信号转导途径方面起着重要作用。线粒体是真核细胞中进行氧化代谢和ATP合成的关键场所,负责糖类、脂质和氨基酸等大分子的代谢。那些特异性定位于线粒体的miRNAs,以及在细胞质中直接或间接调节线粒体特定功能的miRNAs,被称为线粒体miRNAs (mitochondrial miRNAs, mitomiRs)。这些miRNAs能调控相关基因表达,并在关键线粒体代谢途径中发挥独特作用,从而促进肿瘤的发生与发展。本文重点探讨mitomiR在线粒体中的作用以及在肿瘤中的调控机制,旨在进一步阐明肿瘤发生发展的分子机制,开发潜在的癌症新疗法。microRNAs (miRNAs) are a class of short non-coding RNAs typically found in the cytoplasm. They function to regulate post-transcriptional gene expression by binding to the 3' untranslated region (3'UTR) of messenger RNA (mRNA). miRNAs play a crucial role in modulating various metabolic processes and signal transduction pathways. Mitochondria serve as the primary sites for oxidative metabolism and ATP synthesis in eukaryotic cells, and they are responsible for the metabolism of macromolecules, including sugars, lipids, and amino acids. Mitochondrial miRNAs (mitomiRs) are a subset of miRNAs localized specifically within mitochondria and modulate mitochondrial-specific functions, either directly or indirectly, within the cytoplasm. These mitomiRs can modulate gene expression and have a distinct role in pivotal mitochondrial metabolic pathways, thereby influencing the initiation and progression of tumors. This article concentrates on the role of mitomiRs in mitochondria and their regulatory mechanisms in tumorigenesis, with the goal of further elucidating the molecular underpinnings of tumorigenesis and development, and of identifying potential novel therapeutic targets for cancer.
基金Supported by National Research Centre,Egypt,No.E120504.
文摘BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel of circulating microRNAs(miRNAs)independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.METHODS In the present study,we analyzed the aberrant expression of miR-21,miR-221,miR-1246,miR-145,and miR-382,in addition to the tumor biomarkers cancer antigen 15-3(CA15-3)and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in breast cancer patients with varying grades.RESULTS Our results revealed distinct expression patterns of these miRNAs between grade II and III patients.Specifically,miR-21,miR-221,and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG wereobserved in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacyin differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggestingtheir interconnected roles in breast cancer progression. Receiver operating characteristic curve analysisdemonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing thehighest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancergrades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanceddiagnostic accuracy and sensitivity.CONCLUSIONThese findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patientsbased on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting thedevelopment of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management ofbreast cancer patients.
文摘Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,which is further related to successful embryo implantation or conception,either naturally or after assisted reproductive technology.Moreover,this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells(EECs),which results in altered signaling biomolecule secretion,including exosome content.In the context of endometrium regeneration,mesenchymal stromal cells(MSCs)and umbilical cord(UC)-derived stem cells have been applied in clinical trials with promising results.It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs.Specifically,microRNAs in exosomes secreted by the hypoxic damaged EECs,such as miR-214-5p and miR-21-5p,play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3(STAT3)signaling pathway.Taking into consideration the above information,UC-MSCs may be considered as a modern intervention for endometrial regeneration.
文摘Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
文摘Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.
