Diabetes mellitus has become one of the most common chronic diseases,thereby posing a major challenge to global health.Characterized by high levels of blood glucose(hyperglycemia),diabetes usually results from a loss ...Diabetes mellitus has become one of the most common chronic diseases,thereby posing a major challenge to global health.Characterized by high levels of blood glucose(hyperglycemia),diabetes usually results from a loss of insulin-producing β-cells in the pancreas,leading to a deficiency of insulin(type 1 diabetes),or loss of insulin sensitivity(type 2 diabetes).Both types of diabetes have serious secondary complications,such as microvascular abnormalities,cardiovascular dysfunction,and kidney failure.Various complex factors,such as genetic and environmental factors,are associated with the pathophysiology of diabetes.Over the past two decades,the role of small,single-stranded noncoding microRNAs in various metabolic disorders,especially diabetes mellitus and its complications,has gained widespread attention in the scientific community.Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans,these small RNAs post-transcriptionally suppress mRNA target expression.In this review,we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.展开更多
Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recen...Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recent research has highlighted roles for short non-coding microRNAs （miRNAs） in the regulation of stress tolerance. We proposed that they could also play an important role in muscle maintenance during hibernation. To explore this possibility, a group of 10 miRNAs known to be normally expressed in skeletal muscle of non-hibernating mammals were analyzed by RT-PCR in hibernating little brown bats, Myotis lucifugus. We then compared the expression of these miRNAs in euthermic control bats and bats in torpor. Our results showed that compared to euthermic controls, sig- nificant, albeit modest （1.2-1.6 fold）, increases in transcript expression were observed for eight mature miRNAs, including miR-la-1, miR-29b, miR-181b, miR-15a, miR-20a, miR-206 and miR-128-1, in the pectoral muscle of torpid bats. Conversely, expression of miR-21 decreased by 80% during torpor, while expression of miR-107 remained unaffected. Interestingly, these miRNAs have been either validated or predicted to affect multiple muscle-specific factors, including myostatin, FoxO3a, HDAC4 and SMADT, and are likely involved in the preservation of pectoral muscle mass and functionality during bat hibernation.展开更多
Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like pheno...Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-toepithelial transition(MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be thepreferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT(TFs) and the mi RNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and mi RNAs, where mi RNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of mi RNA biogenesis, the ribonuclease type Ⅲ endonuclease Dicer plays a central role in EMTTFs/mi RNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.展开更多
小分子调控RNA,包括siRNA(small interfering RNA)、miRNA(microRNA)和piRNA(piwi interacting RNA)、hsRNA(heterochromatin associated small RNA)等,是当前生命科学研究的前沿热点。越来越多的证据表明,这些小分子R N A存在于几乎所...小分子调控RNA,包括siRNA(small interfering RNA)、miRNA(microRNA)和piRNA(piwi interacting RNA)、hsRNA(heterochromatin associated small RNA)等,是当前生命科学研究的前沿热点。越来越多的证据表明,这些小分子R N A存在于几乎所有较高等的真核生物细胞中,对生物体具有非常重要的调控功能。它们通过各种序列特异性的RNA基因沉默作用,包括RNA干扰(RNAi)、翻译抑制、异染色质形成等,调控诸如生长发育、应激反应、沉默转座子等各种各样的细胞进程。随着对这些小分子调控RNA的发现,一些RNase III酶家族成员、Argonaute蛋白质家族成员及RNA结合蛋白质等先后被鉴定为小RNA的胞内蛋白质合作者,参与小RNA的加工成熟和在细胞内行使功能。本综述简介一些RNA沉默作用途径中重要组分的结构和功能的研究进展。展开更多
Ribonucleic acid （RNA） was previously thought to remain inside cells as an intermediate between genes and proteins during translation. However, it is now estimated that 98% of the mammalian genomic output is transcr...Ribonucleic acid （RNA） was previously thought to remain inside cells as an intermediate between genes and proteins during translation. However, it is now estimated that 98% of the mammalian genomic output is transcribed as noncoding RNAs, which are involved in diverse gene expression regulatory mechanisms and can be transferred from one cell to another through extracellular communication. For instance, microRNAs are 22-nucleotide-long noncoding RNAs that are generated by endonuclease cleavage of precursors inside the cells and are secreted as extracellular microRNAs to regulate target cell posttranscriptional gene expression via RNA interference. We and others have shown that different populations of microRNAs are expressed in distinct regions of the human epididymis and regulate the expression of target genes that are involved in the control of male fertility as indicated by knock-out mouse models. Importantly, some microRNAs, including the microRNA-888 （miR-888） cluster that is exclusively expressed in the reproductive system of human and nonhuman primates, are released in the sperm-surrounding fluid in the epididymis via extracellular vesicles, the so-called epididymosomes. In addition to interacting with the membrane of maturing spermatozoa, these extracellular vesicles containing microRNAs communicate with epithelial cells located downstream from their release site, suggesting a role in the luminal exocrine control of epididymal functions. Apart from their potential roles as mediators of intercellular communication within the epididymis, these extracellular microRNAs are potent molecular targets for the noninvasive diagnosis of male infertility.展开更多
目的通过研究Dicer蛋白表达水平与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)临床病理特征的关系探讨其在OSCC发展过程中的作用。方法利用免疫组化法对76例OSCC、20例白斑、10例癌旁非肿瘤性口腔上皮(normal adjacent to the t...目的通过研究Dicer蛋白表达水平与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)临床病理特征的关系探讨其在OSCC发展过程中的作用。方法利用免疫组化法对76例OSCC、20例白斑、10例癌旁非肿瘤性口腔上皮(normal adjacent to the tumor,NAT)样本的Dicer酶表达进行评估研究。利用Image-Pro Plus 6.0图像分析系统计算平均光密度值(mean optical density,MOD),SPSS 14.0软件系统分析Dicer蛋白MOD、阳性细胞百分比(percentage of positive cells,PP)与临床病理参数的关系。结果 OSCC、白斑组织、NAT的Dicer蛋白MOD、PP依次递减,三者间差异有统计学意义(P<0.05)。Dicer过度表达与肿瘤分期呈正相关关系(P<0.01),与淋巴结转移存在正相关关系(P<0.05),与年龄、性别、分化程度无相关关系。结论 Dicer蛋白表达上调可能通过影响OSCC的生长以及淋巴转移而参与OSCC的发生发展。展开更多
文摘Diabetes mellitus has become one of the most common chronic diseases,thereby posing a major challenge to global health.Characterized by high levels of blood glucose(hyperglycemia),diabetes usually results from a loss of insulin-producing β-cells in the pancreas,leading to a deficiency of insulin(type 1 diabetes),or loss of insulin sensitivity(type 2 diabetes).Both types of diabetes have serious secondary complications,such as microvascular abnormalities,cardiovascular dysfunction,and kidney failure.Various complex factors,such as genetic and environmental factors,are associated with the pathophysiology of diabetes.Over the past two decades,the role of small,single-stranded noncoding microRNAs in various metabolic disorders,especially diabetes mellitus and its complications,has gained widespread attention in the scientific community.Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans,these small RNAs post-transcriptionally suppress mRNA target expression.In this review,we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.
基金supported by a Discovery grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada (Grant No. 6793)
文摘Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recent research has highlighted roles for short non-coding microRNAs （miRNAs） in the regulation of stress tolerance. We proposed that they could also play an important role in muscle maintenance during hibernation. To explore this possibility, a group of 10 miRNAs known to be normally expressed in skeletal muscle of non-hibernating mammals were analyzed by RT-PCR in hibernating little brown bats, Myotis lucifugus. We then compared the expression of these miRNAs in euthermic control bats and bats in torpor. Our results showed that compared to euthermic controls, sig- nificant, albeit modest （1.2-1.6 fold）, increases in transcript expression were observed for eight mature miRNAs, including miR-la-1, miR-29b, miR-181b, miR-15a, miR-20a, miR-206 and miR-128-1, in the pectoral muscle of torpid bats. Conversely, expression of miR-21 decreased by 80% during torpor, while expression of miR-107 remained unaffected. Interestingly, these miRNAs have been either validated or predicted to affect multiple muscle-specific factors, including myostatin, FoxO3a, HDAC4 and SMADT, and are likely involved in the preservation of pectoral muscle mass and functionality during bat hibernation.
基金Supported by The Ligue Nationale contre le Cancer,to Puisieux A
文摘Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-toepithelial transition(MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be thepreferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT(TFs) and the mi RNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and mi RNAs, where mi RNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of mi RNA biogenesis, the ribonuclease type Ⅲ endonuclease Dicer plays a central role in EMTTFs/mi RNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.
文摘Ribonucleic acid （RNA） was previously thought to remain inside cells as an intermediate between genes and proteins during translation. However, it is now estimated that 98% of the mammalian genomic output is transcribed as noncoding RNAs, which are involved in diverse gene expression regulatory mechanisms and can be transferred from one cell to another through extracellular communication. For instance, microRNAs are 22-nucleotide-long noncoding RNAs that are generated by endonuclease cleavage of precursors inside the cells and are secreted as extracellular microRNAs to regulate target cell posttranscriptional gene expression via RNA interference. We and others have shown that different populations of microRNAs are expressed in distinct regions of the human epididymis and regulate the expression of target genes that are involved in the control of male fertility as indicated by knock-out mouse models. Importantly, some microRNAs, including the microRNA-888 （miR-888） cluster that is exclusively expressed in the reproductive system of human and nonhuman primates, are released in the sperm-surrounding fluid in the epididymis via extracellular vesicles, the so-called epididymosomes. In addition to interacting with the membrane of maturing spermatozoa, these extracellular vesicles containing microRNAs communicate with epithelial cells located downstream from their release site, suggesting a role in the luminal exocrine control of epididymal functions. Apart from their potential roles as mediators of intercellular communication within the epididymis, these extracellular microRNAs are potent molecular targets for the noninvasive diagnosis of male infertility.
文摘目的通过研究Dicer蛋白表达水平与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)临床病理特征的关系探讨其在OSCC发展过程中的作用。方法利用免疫组化法对76例OSCC、20例白斑、10例癌旁非肿瘤性口腔上皮(normal adjacent to the tumor,NAT)样本的Dicer酶表达进行评估研究。利用Image-Pro Plus 6.0图像分析系统计算平均光密度值(mean optical density,MOD),SPSS 14.0软件系统分析Dicer蛋白MOD、阳性细胞百分比(percentage of positive cells,PP)与临床病理参数的关系。结果 OSCC、白斑组织、NAT的Dicer蛋白MOD、PP依次递减,三者间差异有统计学意义(P<0.05)。Dicer过度表达与肿瘤分期呈正相关关系(P<0.01),与淋巴结转移存在正相关关系(P<0.05),与年龄、性别、分化程度无相关关系。结论 Dicer蛋白表达上调可能通过影响OSCC的生长以及淋巴转移而参与OSCC的发生发展。
