microRNAs在肝再生中的作用研究进展

目的 microRNAs是一类非编码蛋白的小RNA分子,通过与靶基因mRNA 3’端的非编码区(3’UTRS)结合而在转录后水平调控基因表达,调节细胞增殖、分化、代谢、凋亡、器官发育等生物学过程。肝脏有很强的再生能力,是研究再生的重要材料。因此,我们在文中总结了microRNAs对肝再生调节作用的研究进展。     

microRNAs：小分子在肿瘤中的重要作用

microRNAs是一类新型保守的微小非编码单链RNA,成熟的microRNAs通过与靶基因mRNA碱基形成不完全配对,引起mRNA降解及转录抑制。研究表明,microRNAs对细胞增殖、细胞分化和细胞凋亡具有重要的调控作用,microRNAs的表达异常与肿瘤的发生发展密切相关,肿瘤中既存在肿瘤抑制作用的microRNAs,也存在肿瘤促进作用的microRNAs。因此,microRNAs分子虽小,却在肿瘤发生、发展的过程中作用重大。     

microRNA-155的研究进展

microRNAs是新发现的一类内源性短链非编码RNA分子,成熟的microRNAs规范针对30,50 UTR区,通过与靶基因的特异性相互作用来降解mRNA或者抑制靶基因的翻译,也可以在特定条件下上调     

环状RNA及其在肝病中的作用

环状RNA（circRNA）是一种不具有5’末端帽子结构和3’末端的poly（A）尾巴的新型非编码RNA,是由非共价键形成的反向连接的闭合环状结构。circRNA由于其具有作为miRNA分子海绵及生物标志物的作用,可用于肝脏疾病的治疗和诊断,因此,circ RNA已逐渐成为当今的研究热点。我们针对circRNA以及circRNA在肝病中的研究进行了综述,以期对未来的肝脏疾病的研究和治疗提供理论基础和新思路。     

MicroRNAs与胃癌关系研究进展

MicroRNAs是一类内源性非编码RNA,近年来研究发现,若干microRNAs参与基因调控,直接参与胃癌的发生和分化,microRNAs表达谱与胃癌的进展和预后等密切相关.因此,microRNAs的研究对于阐明胃癌相关基因的功能和胃癌癌变的分子机制具有重要的意义.     

microRNA 在自身免疫及血管炎性疾病发病中的作用

microRNAs(miRNAs)是一类保守的非编码小分子RNA,可与mRNA分子3'非翻译区(UTR)结合,在转录后水平调节多种蛋白质的表达。尽管miRNAs只占人类基因组的3%,却调控大约90%的基因。本文主要阐述在部分自身免疫及系统性血管炎性疾病发病中miRNAs的研究进展。     

神经疾病关联的长链非编码RNA的生物标记物作用

<正>转录组分析显示,只有1%~2%人类基因能编码蛋白质,其余约98%的大部分基因是非编码RNA(non-coding RNAs,ncRNAs)。ncRNA是一类不编码蛋白质但具有生物学功能的RNA分子,根据其长度可将其分为小非编码RNA[包括微小RNA(microRNAs,miRNA)、小干扰RNA(small interfering RNAs,siRNA)等]和长链非编码RNA(long non-cod-     

微小RNAs与心脏发育及疾病

微小RNAs（microRNAs）是一类内源性17~25个核苷酸大小的非编码RNA分子,能调节转录后靶基因的表达,在机体的生长发育、神经分化、细胞增殖、代谢和凋亡等过程中发挥重要作用。研究表明：microRNAs参与了心脏发育,多种miRNAs (miRNA-1, 133, 206 等)基因的表达变化影响心脏的正常发育。microRNAs的水平变化与心律失常、心肌梗死、心肌重构和心力衰竭等心脏疾病的形成亦密切相关。     

微小RNA与肝癌发生发展的研究进展

微dxRNA（microRNAs,miRNA）是一类内源性非编码小RNA分子,miRNA不仅参与各种细胞生理活动（如细胞增殖、分化、凋亡等）,还与肿瘤发生发展关系密切。研究表明miRNA可通过与靶mRNA的3’非编码区互补配对,使得靶mRNA降解或翻译抑制,从而在转录后水平调控基因表达。肝细胞癌是威胁人类健康的恶性肿瘤之一,深入了解miRNA及其在肝细胞癌进程中的作用,将为HCC的分子机制研究提供新的思路。     

长链非编码RNA参与调控成骨细胞分化和破骨细胞的生成

文题释义： 长链非编码RNA(Lnc RNA)：是长度超过200个核苷酸的RNA分子,缺乏明显的开放阅读框,不具有或具有少许蛋白编码功能。 骨关节炎：是一种慢性退行性关节病,主要表现为关节软骨的退化、软骨下骨的改变、邻近骨的广泛重塑以及骨赘的形成。 背景：长链非编码RNA能够在转录及转录后水平等多个方面发挥作用,参与骨再生的调控,同时与骨关节炎有着密切的联系。 目的：综述长链非编码RNA在骨再生和骨关节炎中的研究进展。 方法：计算机检索CNKI数据库、PubMed数据库以及Elsevier数据库的相关文献,中文检索词为：长链非编码RNA,骨,骨再生,骨关节炎;英文检索词为：LncRNA,bone,bone regeneration,osteoarthritis。查阅2000年1月至2019年6月期间收录的长链非编码RNA在骨再生和骨关节炎方面的研究和应用,包括综述、基础研究以及临床研究。通过阅读文题和摘要进行初步筛选,排除与文章主题不相关的文献,根据纳入标准和排除标准,最终纳入64篇文献进行结果分析。 结果与结论：①骨再生是一个涉及到成骨细胞和破骨细胞相互作用的复杂过程,长链非编码RNA参与成骨细胞的分化和破骨细胞的生成,对成骨细胞和破骨细胞的平衡起着重要的作用,因此是骨再生过程中的关键分子;②长链非编码RNA参与了骨关节炎的发生和发展,长链非编码RNA的表达在骨关节炎患者和健康人群中有着明显的差异,在骨关节炎患者中一些长链非编码RNA的表达升高,部分表达降低,明确各自的表达差异和功能对预防和治疗骨关节炎意义重大。 ORCID: 0000-0002-6311-4748(熊坤) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Circulating microRNAs: A Potential Role in Diagnosis and Prognosis of Acute Myocardial Infarction

Rapid and correct diagnosis of acute myocardial infarction (AMI) plays a crucial role in saving patients'' life. Although some biomarkers (such as cardiac troponin and creatine kinase) are available for AMI diagnosis so far, there is still a clinical need for novel biomarkers, which can reliably rule in or rule out AMI immediately on admission. Circulating microRNAs (miRNAs) are a potential choice for novel biomarkers in AMI diagnosis and prognosis with high sensitivity and specificity. Circulating microRNAs are endogenous miRNAs that are detectable in whole blood, serum, or plasma in a highly stable form. Until now, around 20 circulating miRNAs were reported to be closely associated with AMI. In this minireview, we summarized recent available data on the correlation between circulating miRNAs and AMI. Some miRNAs, such as miR-208, miR-499, miR-133, and miR-1, were given special attention, since they may have a potential prospect in diagnosis and prognosis of AMI.     

微小RNAs在涡虫再生中的研究进展

涡虫由于其体内存在丰富的成体干细胞——新母细胞（neoblasts）而具有极强的再生能力。目前,涡虫已成为再生生物学研究的重要模式动物,neoblasts也成为生物医学领域的重要工具细胞。但关于调控涡虫再生和neoblasts增殖的基因网络仍不十分清楚。微小RNAs（miRNAs）是广泛存在于真核生物中的一类内源性、小片段、非编码RNA,可通过特异性识别并结合目的RNA,负调控功能基因的表达。近期的研究提示,miRNAs可能参与涡虫再生的调控。我们就miRNAs调控涡虫再生及neoblasts,增殖和分化特性的新近研究成果及进展进行综述。     

Dynamic miRNA expression patterns during retinal regeneration in zebrafish: Reduced dicer or miRNA expression suppresses proliferation of Müller Glia‐derived neuronal progenitor cells

Background: Adult zebrafish spontaneously regenerate their retinas after damage. Although a number of genes and signaling pathways involved in regeneration have been identified, the exact mechanisms regulating various aspects of regeneration are unclear. microRNAs (miRNAs) were examined for their potential roles in regulating zebrafish retinal regeneration. Results: To investigate the requirement of miRNAs during zebrafish retinal regeneration, we knocked down the expression of Dicer in retinas prior to light‐induced damage. Reduced Dicer expression significantly decreased the number of proliferating Müller glia‐derived neuronal progenitor cells during regeneration. To identify individual miRNAs with roles in neuronal progenitor cell proliferation, we collected retinas at different stages of light damage and performed small RNA high‐throughput sequencing. We identified subsets of miRNAs that were differentially expressed during active regeneration but returned to basal levels once regeneration was completed. We then knocked down five different miRNAs that increased in expression and assessed the effects on retinal regeneration. Reduction of miR‐142b and miR‐146a expression significantly reduced INL proliferation at 51h of light treatment, while knockdown of miR‐7a, miR‐27c, and miR‐31 expression significantly reduced INL proliferation at 72h of constant light. Conclusions: miRNAs exhibit dynamic expression profiles during retinal regeneration and are necessary for neuronal progenitor cell proliferation. Developmental Dynamics 243:1591–1605, 2014. © 2014 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists     

减体积肝移植模型大鼠肝脏组织miRNAs表达谱变化

BACKGROUND: Liver regeneration is the key factor influencing the prognosis of living donor liver transplantation. There has not been the research on special miRNA of liver regeneration after living donor liver transplantation. OBJECTIVE: To analyze the variation of miRNAs expression profile after rat reduced-size liver transplantation at certain time point, select and verify target miRNA which can provide targeting intervention strategies in liver regeneration after rat reduced-size liver transplantation and provide theoretical evidence for liver regeneration after living donor liver transplantation. METHODS: The reduced-size liver transplantation models were established. miRNAs microarray was used to detect miRNA expression. In differentially expressed microRNAs, real-time quantitative PCR was utilized to detect target miRNAs. The credibility of miRNAs microarray results was verified. RESULTS AND CONCLUSION: Compared with rat liver tissue in the sham operation group, 11 miRNAs up-regulated in reduced-size liver transplantation, including let-7b-5p, let-7c-5p, miR-101a-3p, miR-103-3p, miR-130a-3p, miR-142-5p, miR-186-5p, miR-199a-3p, miR-21-5p, 221-3p and miR-34a-5p. Four miRNAs were down-regulated, including miR-26b-5p, miR-150-5p, miR-19a-3p and rno-miR-146-5p. PCR test further verified that miR-221-3p and miR-199a-3p expression changes approximated the chip results at 24, 48 hours and 1 week, indicating that results of miRNA microarray were believable. These results verified that it exists variation of miRNAs expression profile after rat reduced-size liver transplantation, which picked out and verified the target miRNAs.        

microRNA对周围神经再生的调控作用

microRNA(miRNA)是高度保守的内源性非编码RNA,在多种生理和病理过程中起着重要的作用。周围神经损伤后,许多miRNA的表达发生显著变化。差异表达的miRNA负向调控其靶基因的表达,从而影响受损周围神经的再生和重塑。本综述从miRNA对神经元、施万细胞、失神经支配肌肉等的影响,阐明miRNA在周围神经过程中的调控作用。对于miRNA在周围神经损伤和再生过程中作用的研究,有助于更好地理解周围神经损伤后的内在分子调控机制,为将miRNA作为临床治疗的靶点提供了坚实的基础。     

MicroRNA dysregulation in response to RARβ2 inhibition reveals a negative feedback loop between MicroRNAs 1, 133a,and RARβ2 during tail and spinal cord regeneration in the adult newt

Background: The molecular events underlying epimorphic regeneration of the adult urodele amphibian tail and caudal spinal cord are undetermined. Given the dynamic nature of gene expression control by retinoic acid (RA) signaling and the pleiotropic effects of microRNAs (miRNAs) on multiple mRNA targets in this complex system, we examined whether RA signaling through a specific receptor, RARβ2, alters expression of select miRNAs during spinal cord regeneration. Results: An initial screen identified 18 highly conserved miRNAs dysregulated in regenerating tail and spinal cord tissues after inhibition of RARβ2 signaling with a selective antagonist, LE135. miRNAs let‐7c, miR‐1, and miR‐223 were expressed within the ependymoglial cells, coincident spatially with the expression of RARβ2. Altering the expression pattern of these three miRNAs led to a significant inhibition of caudal ependymal tube outgrowth by 21 days post tail amputation. We demonstrated that miR‐1 targets the 3′‐untranslated region of RARβ2 mRNA in vitro; and in vivo, up‐regulation of miR‐1 led to a significant decrease in RARβ2 protein. Conclusions: These and previous data suggest that miR‐1 and miR‐133a, both members of the same miRNA gene cluster, may participate with RARβ2 in a negative feedback loop contributing to the regulation of the ependymal response after tail amputation. Developmental Dynamics 244:1519–1537, 2015. © 2015 Wiley Periodicals, Inc.     

Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients

Objectives: Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection.Methods: Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR-134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection.Results: miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR-629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation.Conclusion: HCV patients have a broad ''fingerprint'' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation.     

Induction of cancer-related microRNA expression profiling using excretory-secretory products of Clonorchis sinensis

Clonorchis sinensis is a carcinogenic human liver fluke by which chronic infection is strongly associated with the development of cholangiocarcinoma. Although this cholangiocarcinoma is caused by both physical and chemical irritation from direct contact with adult worms and their excretory–secretory products (ESPs), the precise molecular events of the host–pathogen interactions remain to be elucidated. To better understand the effect of C. sinensis infection on cholangiocarcinogenesis, we profiled the kinetics of changes in cancer-related microRNAs (miRNAs) in human cholangiocarcinoma cells (HuCCT1) treated with C. sinensis ESPs for different periods. Using miRNA microarray chips containing 135 cancer-related miRNAs, we identified 16 miRNAs showing differentially altered expression following ESP exposure. Of these miRNAs, 13 were upregulated and 3 were downregulated in a time-dependent manner compared with untreated controls. Functional clustering of these dysregulated miRNAs revealed involvement in cell proliferation, inflammation, oncogene activation/suppression, migration/invasion/metastasis, and DNA methylation. In particular, decreased expression of let-7i, a tumor suppressor miRNA, was found to be associated with the ESP-induced upregulation of TLR4 mRNA and protein, which contribute to host immune responses against liver fluke infection. Further real-time quantitative PCR analysis using ESP-treated normal cholangiocytes (H69) revealed that the expressions of nine miRNAs (miR-16-2, miR-93, miR-95, miR-153, miR-195, miR-199-3P, let7a, let7i, and miR-124a) were similarly regulated, indicating that the cell proliferation and inhibition of tumor suppression mediated by these miRNAs is common to both cancerous and non-cancerous cells. These findings constitute further our understanding of the multiple cholangiocarcinogenic pathways triggered by liver fluke infection.     

Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish

Appendage regeneration is defined by rapid changes in gene expression that achieve dramatic developmental effects, suggesting involvement of microRNAs (miRNAs). Here, we find dynamic regulation of many miRNAs during zebrafish fin regeneration. In particular, miR-133 levels are high in uninjured fins but low during regeneration. When regeneration was blocked by Fibroblast growth factor (Fgf) receptor inhibition, high miR-133 levels were quickly restored. Experimentally increasing amounts of miR-133 attenuated fin regeneration. Conversely, miR-133 antagonism during Fgf receptor inhibition accelerated regeneration through increased proliferation within the regeneration blastema. The Mps1 kinase, an established positive regulator of blastemal proliferation, is an in vivo target of miR-133. Our findings identify miRNA depletion as a new regulatory mechanism for complex tissue regeneration.     

Serum aca-mir-146a is a potential biomarker for early diagnosis of Angiostrongylus cantonensis infection

Infection with Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis, but it lacks an effective early diagnostic tool for the disease. Recently, growing number of serum microRNAs (miRNAs) were investigated to serve as potentially noninvasive biomarkers for various diseases. However, it is unclear if the molecule can considered a biomarker for diagnosing the infection of A. cantonensis. Here, we attempted to identify potential A. cantonensis-derived miRNAs for the early diagnosis of angiostrongyliasis. Through Solexa deep sequencing and GO “biological process” classifications, we found that there were 18 miRNAs of significantly differential expression in the fourth-stage larvae (L4) larva of A. cantonensis when compared with the third-stage larvae (L3) larva of A. cantonensis. Among the 18 miRNAs, the sequences of 6 miRNAs, including aca-miR-29a, aca-miR-124, aca-miR-125a, aca-miR-146a, aca-miR-101, and aca-miR-185, were different from human- and mouse-derived miRNAs (both are the nonpermissive hosts of A. cantonensis). The expression patterns of the six A. cantonensis-derived miRNAs in serum were investigated by polymerase chain reaction on the A. cantonensis-infected mice and their controls. We found that aca-miR-146a had a significantly higher expression level in every experimental positive group, which suggested that this miRNA might be useful for early diagnosis. Receiver operating characteristic (ROC) curve analysis showed that aca-miR-146a was an effective biomarker for discriminating A. cantonensis-infected mice from healthy control cases, with an area under the ROC curve (AUC) of 0.90. Its diagnostic accuracy was assessed on patients (n?=?30) and healthy controls (n?=?30), and the sensitivity and specificity reached 83 and 86.7 %, respectively. Our study revealed that aca-mir-146a in serum is an effective biomarker to track infection of A. cantonensis.