Micro RNAs与急性心肌梗死关系的研究进展

急性心肌梗死(acute myocardial infarction,AMI)是冠状动脉疾病最严重的表现,其引起的心肌组织损伤可促进心力衰竭的发展。尽管近些年由于生活方式的改变、治疗方式(如经皮冠状动脉介入治疗)的发展使AMI的预后得到了改善,但是AMI依旧每年危害着全球700多万人的身心健康,AMI仍然是世界范围内高发病率和高死亡率的主要疾病之一[1]。微小RNA(micro RNAs,miRNAs)是在20世纪90年代被发现的,mi RNAs的研究已经迅速发展成为一个成熟而广阔的领域。mi RNAs存在于几乎所有类型的细胞和细胞的病理生理活动中,包括与心血管系统相关的细胞。本文将mi RNAs对AMI病理生理进程的影响进行综述,希望为临床治疗提供新思路。

Genome-wide Investigation of micro RNAs and Their Targets in Brassica rapa ssp. pekinensis Root with Plasmodiophora brassicae Infection

Increasing evidence has revealed that micro RNAs play a pivotal role in the post transcriptional regulation of gene expression in response to pathogens in plants. However, there is little information available about the expression patterns of mi RNAs and their targets in Chinese cabbage(Brassica rapa ssp. pekinensis) under Plasmodiophora brassicae stress. In the present study, using deep sequencing and degradome analysis, a genome-wide identification of mi RNAs and their targets during P. brassicae stress was performed. A total of 221 known and 93 potentially novel mi RNAs were successfully identified from two root libraries of one control(635-10CK) and P. brassicae-treated Chinese cabbage samples(635-10T). Of these, 14 known and 10 potentially novel mi RNAs were found to be differentially expressed after P. brassicae treatment. Degradome analysis revealed that the 223 target genes of the 75 mi RNAs could be potentially cleaved. KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway analysis suggested that the putative target genes of the mi RNAs were predominately involved in selenocompound metabolism and plant hormone signal transduction. Then the expression of 12 mi RNAs was validated by quantitative real-time PCR(q RT-PCR). These results provide insights into the mi RNA-mediated regulatory networks underlying the stress response to the plant pathogen P. brassicae.

Micro RNAs in colorectal cancer

Introduction In 2008 over 1.2 million new cases along with 608 700 estimated CRC-associated deaths have occurred.In China,where it is now the third most common malignancy and the fifth leading cause of cancer-related death,the incidence of CRC is still increasing even with the improvements in the standard of living and changes in lifestyle.Despite improvements in

Identification of micro RNAs in six solanaceous plants and their potential link with phosphate and mycorrhizal signalings

To date, only a limited number of solanaceous miRNAs have been deposited in the miRNA database. Here,Rgenome-wide bioinformatic identification of miRNAs was performed in six solanaceous plants（potato, tomato, tobacco,eggplant, pepper, and petunia）. A total of 2,239 miRNAs were identified following a range of criteria, of which 982 were from potato, 496 from tomato, 655 from tobacco, 46 from eggplant,45 were from pepper, and 15 from petunia. The sizes of miRNA families and miRNA precursor length differ in all the species.Accordingly, 620 targets were predicted, which could be functionally classified as transcription factors, metabolic enzymes, RNA and protein processing proteins, and other proteins for plant growth and development. We also showed evidence for miRNA clusters and sense and antisense miR NAs.Additionally, five Pi starvation- and one arbuscular mycorrhiza（AM）-related cis-elements were found widely distributed in the putative promoter regions of the miRNA genes. Selected miRNAs were classified into three groups based on the presence or absence of P1BS and MYCScis-elements, and their expression in response to Pi starvation and AM symbiosis was validated by quantitative reverse transcription-polymerase chain reaction（qRT-PCR）. These results show that conserved miRNAs exist in solanaceous species and they might play pivotal roles in plant growth, development, and stress responses.

Micro-RNAs Regulate Metabolic Syndrome-induced Senescence in Adipose Tissue-derived Mesenchymal Stem Cells of through P16/MAPK Pathway

Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome(Met S)show decreased vitality.A growing number of micro RNAs(mi RNAs)are recognized as key modulators of senescence,but their role in regulating senescence in MSC in Mets is unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet(n=6 each).Next-generation mi RNA sequencing(mi RNA-seq)was performed to identify mi RNAs up-or down-regulated in Met S-MSC compare to Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We found the 7 upregulated mi RNAs,including mi R-27b,and 3 downregulated mi RNAs in Met S-MSCs,which regulate 35 SA genes,particularly MAPK signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions Met S modulate MSC expression of SA-mi RNAs that may play the role in modulating their senescence,and the p16 pathway in Met S-MSCs senescence is the primary pathway.

脑梗死患者血micro RNA表达水平对预后的影响

目的探讨脑梗死患者血micro RNA(miRNA)表达水平对预后的影响。方法选取邯郸市中心医院和安国市医院收治的63例急性脑梗死患者临床资料,分为两组,预后良好组31例,预后不良组32例。收集患者的一般资料,采集患者治疗前外周静脉血予以实时荧光定量-聚合酶链式反应(qPCR)检测miR-124、miR-125b、miR-126、miR-223、miR-422、miR-221、miR-335等miRNA的表达水平,进行多因素Logistic回归分析预后的影响因素。结果两组患者吸烟、NIHSS评分之间差异有统计学意义(χ^(2)/t=7.746、16.387,P<0.05)。预后良好组的miR-124、miR-125b、miR-126、miR-422、miR-221、miR-335水平显著低于预后不良组,而miR-223显著高于预后不良组,差异有统计学意义(t=8.421、6.348、5.434、9.847、7.987、10.346、7.652,P<0.05);miR-124、miR-125b、miR-126、miR-422、miR-221、miR-335、NIHSS评分均是影响不同预后的因素[OR(95%CI)=8.303(1.226~2.375)、4.241(1.119~6.890)、4.953(1.106~2.421)、4.860(0.316~5.900)、4.746(1.110~7.033)、6.677(0.266~8.219)、1.496(1.009~2.219),P<0.05]。结论不同预后的脑梗死患者外周血miRNA表达水平存在差异,对患者miR-124、miR-125b、miR-126、miR-422、miR-221、miR-335等指标进行监测,有助于观察患者的临床疗效及预后。

microRNA-34a在肝病发生发展中的作用

microRNA是一种小的非编码RNA,通过对各种靶基因的负调控参与细胞的增殖和凋亡等环节。目前越来越多证据表明,microRNA-34a参与非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)、酒精性肝病(alcoholic liver disease, ALD)、肝纤维化等多种肝脏疾的发生发展过程,尤其在肝癌方面发挥着重要作用;此外,中药单体或中药复方可以通过microRNA-34a对肝脏疾病进行调节。microRNA-34a作为无创生物学标志物为肝脏疾病的诊疗提供参考。

MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

Epithelial ovarian cancer(EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers(mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as micro RNAs(miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish mi RNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers.

Micro RNA在缺血性卒中后炎症反应中的研究进展

Micro RNA(miRNA)是一类小型非编码RNA,是控制正常和患病大脑各种功能所必需的基因调节因子,其正常表达对于维持大脑的正常功能是必不可少的。脑缺血后,多种miRNAs的表达水平发生了显著变化,并在脑卒中的病理生理过程中发挥了重要作用。近年来,miRNAs在脑缺血后炎症反应中的重要调控作用逐渐受到重视,其对神经元、小胶质细胞、星形胶质细胞、少突胶质细胞等的调控作用也逐渐清晰。

Noncoding RNAs as drivers of the phenotypic plasticity of oesophageal mucosa

The histological commitment of the lower oesophageal mucosa largely depends on a complex molecular landscape. After extended inflammatory insult due to gastroesophageal reflux disease,squamous oesophageal mucosa may differentiate into columnar metaplastic mucosa. In this setting,the presence of intestinal metaplasia is considered the starting point of Barrett's carcinogenetic cascade. Aside from secondary prevention strategies for Barrett's mucosa(BM) patients,there are multiple endoscopic ablative therapies available for BM eradication and for the replacement of metaplastic epithelia with a neosquamous mucosa. However,BM frequently recurs in a few years,which supports the notable phenotypic plasticity of the oesophageal mucosa. In recent years,several reports pinpointed a class of small noncoding RNAs,the micro RNAs(mi RNAs),as principal effectors and regulators of oesophageal mucosa metaplastic(and neoplastic) transformation. Because of mi RNAs notable stability in fixed archival diagnostic specimens,expression profiling of mi RNAs represent an innovative diagnostic,prognostic and predictive tool in the stratification of phenotypic alterations in the oesophageal mucosa.

Validation of a serum microRNA panel as biomarkers for early diagnosis of hepatocellular carcinoma post-hepatitis C infection in Egyptian patients

AIM To investigate the prospective importance of serum micro(mi)RNAs(mi R-125 b, mi R-138 b, mi R-1269, mi R-214-5p, mi R-494, mi R375 and mi R-145) as early biomarkers for the diagnosis of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS Two-hundred and fifty HCV4 a patients, 224 HCV4 aHCC patients, and 84 healthy controls were enrolled in the study. Expression levels of mi R214-5p, mi R-125 b, mi R-1269 and mi R-375 were quantified using quantitative real-time PCR.RESULTS Expression of the selected mi RNAs in serum wassignificantly lower in HCC patients than in the healthy controls, except for mi R-1269 and mi R-494. There was a significant difference between HCC and HCV patients, in particular for HCC and late stage fibrosis, rather than HCV patients and early fibrosis. It is obvious that mi R-1269 was significantly upregulated in HCC cases compared to hepatic fibrosis cases. Each mi RNA can show HCC progression. Multivariate logistic regression analysis indicated that the tested panel of mi RNAs(mi R214-5p, mi R-125 b, mi R-1269 and mi R-375) represent accurate and specific indictors of HCC development.CONCLUSION This study presents a panel of mi RNAs with strong power as putative diagnostic and prognostic biomarkers for HCV-induced HCC. Moreover, mi R-214-5p and mi R-1269 could be considered as early biomarkers for tracking the progress of liver fibrosis to HCC.

Inhibition of Micro RNA 219 Expression Protects Synaptic Plasticity via Activating NMDAR1, Ca MKIIγ,and p-CREB after Microwave Radiation

In recent decades,the potential health hazards of microwave exposure have been attracting increasing attention.Our previous studies have demonstrated that microwave exposure impaired learning and memory in experimental animal models[1,2].

Role of mitochondria in regulating micro RNA activity and its relevance to the central nervous system

Mitochondria serve as the powerhouse of cells,respond to cellular demands and stressors,and play an essential role in cell signaling,differentiation,and survival.Aberrant mitochondria function has been linked to diverse and complex human diseases such as neurodegenerative diseases,cancers,myopathies,premature aging,and metabolic syndromes（Nunnari and Suomalainen,2012）.

Regulatory role of microRNA on inflammatory responses of diabetic retinopathy

The prevalence of diabetes has been increasing in the U.S., with diabetes as a significant concern for patients＇ physical and financial health. Diabetic retinopathy is the leading cause of vi- sual loss in working-age of adults and is characterized by retinal neurodegeneration and microvascular abnormalities in the eye. Hyperglycemia is one significant risk factor for diabetic retinop- athy and can result in increased inflammatory responses and vascular dysfunction. However, the molecular mechanisms un-derlying these pathologies are not fully understood. Although treatments are currently available for the patients with prolif-erative diabetic retinopathy or macular edema, including laser photocoagulation, steroids, or anti-vascular endothelial growth factor （VEGF） injections, many patients fail to respond to these therapies. Therefore, it is imperative to develop additional novel therapeutics for diabetic retinopathy.

Loss of micro RNA-124 expression in neurons in the peri-lesion area in mice with spinal cord injury

Micro RNA-124（mi R-124） is abundantly expressed in neurons in the mammalian central nervous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and postnatal neural differentiation. However, the expression profile of mi R-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of mi R-124 in mouse brain and spinal cord after spinal cord injury using in situ hybridization. Furthermore, the expression of mi R-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The mi R-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with Neu N immunohistochemical staining. The mi R-124 was mainly expressed in neurons throughout the brain and spinal cord. The expression of mi R-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were Neu N＋/mi R-124-. Moreover, the neurons distal to the peri-lesion site were Neu N＋/mi R-124＋. These findings indicate that mi R-124 expression in neurons is reduced after spinal cord injury, and may reflect the severity of spinal cord injury.

Valproic acid as a micro RNA modulator to promote neurite outgrowth

Valproic acid （VPA） has been a first-choice drug for clinical treatment of epilepsy and manic disorder. For decades, its phar- macological action was believed to act on inhibition of gam- ma-aminobutyric acid （GABA） transaminase, in turn, increas- ing GABA in inhibitory synapses. However, in recent years, VPA has been investigated on other therapeutic actions. Those investigations demonstrate that VPA shows neuroprotective ef- fects by promoting neurogenesis, neuronal differentiation, and neuroregeneration （Foti et al., 2013）.

MicroRNA-regulated viral vectors for gene therapy

Safe and effective gene therapy approaches require targeted tissue-specific transfer of a therapeutic transgene.Besides traditional approaches, such as transcriptional and transductional targeting, micro RNA-dependent posttranscriptional suppression of transgene expression has been emerging as powerful new technology to increase the specificity of vector-mediated transgene expression. Micro RNAs are small non-coding RNAs and often expressed in a tissue-, lineage-, activation- or differentiation-specific pattern. They typically regulate gene expression by binding to imperfectly complementary sequences in the 3' untranslated region(UTR) of the m RNA. To control exogenous transgene expression, tandem repeats of artificial micro RNA target sites are usually incorporated into the 3' UTR of the transgene expression cassette, leading to subsequent degradation of transgene m RNA in cel s expressing the corresponding micro RNA. This targeting strategy, first shown for lentiviral vectors in antigen presenting cells, has now been used for tissue-specific expression of vector-encoded therapeutic transgenes, to reduce immune response against the transgene, to control virus tropism for oncolytic virotherapy, to increase safety of live attenuated virus vaccines and to identify and select cell subsets for pluripotent stem cell therapies, respectively. This review provides an introduction into the technical mechanism underlying micro RNA-regulation, highlights new developments in this field and gives an overview of applications of micro RNA-regulated viral vectors for cardiac, suicide gene cancer and hematopoietic stem cell therapy, as well as for treatment of neurological and eye diseases.

Altered microRNA expression profiles in a rat model of spina bifida

Micro RNAs（mi RNAs） are dynamically regulated during neurodevelopment,yet few reports have examined their role in spina bifida.In this study,we used an established fetal rat model of spina bifida induced by intragastrically administering olive oil-containing all-trans retinoic acid to dams on day 10 of pregnancy.Dams that received intragastric administration of all-trans retinoic acid-free olive oil served as controls.The mi RNA expression profile in the amniotic fluid of rats at 20 days of pregnancy was analyzed using an mi RNA microarray assay.Compared with that in control fetuses,the expression of mi RNA-9,mi RNA-124 a,and mi RNA-138 was significantly decreased（〉 2-fold）,whereas the expression of mi RNA-134 was significantly increased（〉 4-fold） in the amniotic fluid of rats with fetuses modeling spina bifida.These results were validated using real-time quantitative reverse-transcription polymerase chain reaction.Hierarchical clustering analysis of the microarray data showed that these differentially expressed mi RNAs could distinguish fetuses modeling spina bifida from control fetuses.Our bioinformatics analysis suggested that these differentially expressed mi RNAs were associated with many cytological pathways,including a nervous system development signaling pathway.These findings indicate that further studies are warranted examining the role of mi RNAs through their regulation of a variety of cell functional pathways in the pathogenesis of spina bifida.Such studies may provide novel targets for the early diagnosis and treatment of spina bifida.

MicroRNAs标志物在子痫前期胎盘组织中的表达

目的探讨血清MicroRNAs标志物在子痫前期胎盘组织中的表达及变化的意义。方法选择2019年7月—2020年7月在河源市和平县人民医院就诊的60例确诊为子痫前期孕妇为子痫前期组,另选60例同期排除子痫前期的孕妇为对照组,测量两组患者血压,24 h尿蛋白定量,采用real-time PCR检测两组患者的胎盘组织中的miR-210、miR-181a、miR-222、miR-26b、miR-377、miR-455的水平,并将所获得数据进行比较。结果通过比较发现,对照组5.00%孕妇为高血压,0.00%孕妇尿蛋白定量高于0.15g/24 h;子痫前期组80.00%孕妇为高血压,90.00%尿蛋白定量高于0.15g/24 h,组间比较差异均有统计学意义(P<0.05)。子痫前期组患者miR-210、miR-181a、miR-222、miR-26b水平明显高于对照组,miR-377、miR-455的水平明显低于对照组,差异均有统计学意义(P<0.05)。结论在子痫前期患者的胎盘组织中不同类型的MicroRNAs水平发生改变,通过血清MicroRNAs标志物水平检测可以提高子痫前期的诊断率,保障降低孕妇及胎儿安全风险,具有很好的应用前景。

Role of Dicer on tumorigenesis in glioma cells

Micro RNAs（miRNAs）are non-coding,single-stranded RNAs that regulate target gene expression by repressing translation or promoting RNA cleavage.Recent studies show that miRNA expression is globally decreased in some human tumors.Dicer is an essential component of the miRNA processing machinery.To determine whether global reduction of miRNA effects tumorigenesis,small interfering RNA were designed to target Dicer to restrain whole miRNA expression in the glioblastoma cell line-TJ905.With effective knock-down of Dicer,tumor cells were invasive and proliferative,and globally impaired miRNA processing enhanced proliferation and invasiveness of glioma cells in vitro.Suppression of Dicer expression resulted in a more aggressive glioma phenotype,which suggests that global reduction of miRNA expression could have an oncogenic role in glioblastoma cells.