沉默miR-135b降低宫颈癌HeLa细胞系增殖和迁移

正microRNAs是一种长度约为21~23个核苷酸的内源性RNA,通过与mRNAs的3'UTR互补配对抑制蛋白质的转录,从而调控动植物生长发育中的基因表达~([1])。miR-135b被发现在多种癌症的发生发展中作为癌基因或抑癌基因,其异常表达与多种肿瘤的发生密切相关,但结果不具有一致性。已     

长链非编码RNA在急性髓系白血病中调控机制的研究进展

<正>长链非编码RNA(long non-coding RNA,lncRNA)是指长度大于200个核苷酸的非编码RNA,起初它被认为是基因组转录的"噪音",即RNA聚合酶Ⅱ转录的副产物,并不具有生物学功能~([1-2])。但随着研究的深入,人们发现lncRNA参与了X染色体沉默、表观遗传调控、转录激活与干扰、细胞分化调节等多个关键的调控过程~([3-5])。研究表明,lncRNA的异常,包括     

生物信息学分析mircoRNA在乳腺癌中的调控网络

<正>生物信息学是指综合应用信息科学、数学的理论、方法和技术来管理、分析和利用生物分子数据的一门科学。科学地利用生物分子数据及其分析结果,可以大大提高研究和开发的科学性及效率~([1])。miRNA(mircoR NA)是一类由内源基因编码的长度为20~24个核苷酸的非编码单链小分子RNA。miRNA能够与靶信使RNAs(mRNAs)3'-端非翻译区(3'-UTR)互补配对,阻碍mRNA翻译或使其稳定性降低而被降解,从而参与到转录后调控~([2])。近年许多研究表明,     

miR-221/miR-222在人甲状腺乳头状癌中的表达增加

正miR-221/miR-222是近几年发现的一类广泛存在于真核生物中、长度约22个核苷酸、进化上高度保守、具有转录后负性调节作用的小分子非编码RNA~([1]),能够负性调节该基因的蛋白表达,进而参与多种重要的细胞传导途径和生理病理过程~([1])。本研究通过分析不同甲状腺组织miR-221/miR-222的表达,探讨miR-221/miR-222在甲状腺癌发     

长链非编码RNA MEG3 调控作用相关的信号通路研究进展

正随着基因组学的不断发展,越来越多的研究表明lncRNA表达水平的改变与疾病的发展和状态有明显的联系,尤其在肿瘤中发挥举足轻重的作用~([1])。LncRNA是长度大于200个核苷酸的转录RNA,保守性低,在体内通过控制蛋白质的合成、RNA的成熟和转运以及改变染色体结构从而使转录基因沉默等机制发挥调控作用~([2])。MEG3是一类重要的lncRNA,具有肿瘤抑制作用~([3]),有望成为肿瘤诊断的生物标志物和肿瘤治疗的靶点,以下就MEG3在肿瘤及多种相关疾病关系密切的信号通路的作用及其机制作一综述。     

牛磺酸上调基因1对肿瘤发生发展的调控作用

<正>基因的失调控(异常表达)是肿瘤发生发展的重要原因(诱因)业已被学术界所公认,而在这一过程中非编码RNA(non-coding RNA,ncRNA)起到了极为重要的调控作用~([1-2])。小RNA(small RNA;包括微小RNA,microRNA,miRNA,miR)和长链非编码RNA(long non-coding RNA,lncRNA)均属于ncRNA~([3-4])。     

氟西汀治疗抑郁症的疗效综述

正1概述抑郁症是一种重性精神障碍,以抑郁心境为主要表现,具有高发病率和高死亡率的显著特点,可发生于任何年龄与种族~([1-4])。全球每5个人中就有1人一生中受到抑郁症的影响~([5])。根据世界卫生组织的最新估计,目前有3亿多人罹患抑郁症,从2005-2015年,增加了18%以上~([6])。其终生患病率为4.4%~18%~([7-9]),成年人中平均每年有5%~     

儿童专科医院特色生物样本库的建立与应用

<正>生物样本库是一种集中收集、处理、存储和应用各种生物材料及其相关信息用于疾病的临床诊疗研究的生物应用系统~([1])。一般由两部分组成:一是样本实体库,即可以从中提取到DNA、RNA、蛋白质等成分的组织或血液等生物样本;二是样本信息库,包括从生物样本中提取DNA、RNA、蛋白质等成分所得到的个人独有的遗传信息数据及临床诊疗信息~([2])。早在1994年,中国科学院就建立了中华民族永生细胞     

西红花苷促进小鼠脾淋巴细胞增殖

正西红花苷(crocin)是从栀子和西红花2种传统中药材中提取的水溶性类胡萝卜素,是这2种中药材的主要药理活性成份。它水溶性好,容易被机体吸收,生物利用度高,西红花苷具有广泛的药理活性,是一种高效的抗氧化剂~([1])、此外,它还具有保护心血管~([2])、抗炎~([3-4])、神经保护~([5-7])及机体免疫力的作用~([8]),同时研究还发现西红花苷是一种天然肿瘤抑制剂,可以诱导多种肿瘤细胞发生凋亡,发挥抗肿瘤     

基于代谢组学的PM_(2.5)对代谢途径影响的研究进展

正细颗粒物(fine particulate matter/particulate matter 2.5,PM_(2.5))作为普遍存在的空气污染物之一,是影响人类健康的重要危险因素~([1])。PM_(2.5)体积小,表面积大,易吸附重金属、多环芳烃、微生物等有毒有害成分,对人体造成危害,引起了人们极大关注~([2])。许多流行病学研究都表明PM_(2.5)会增加人类患各种疾病的风险,包括心血管疾病~([3])、呼吸系统疾病~([4])、早产和低出生体重~([4])、糖尿病~([5])、神经毒性~([6])和肾功能损害~([7])等。     

MiR-494通过核转录因子-κB通路对脓毒症大鼠肾损伤的作用机制

目的：探讨miR-494 通过核转录因子-κB(NF-κB) 通路对脓毒症大鼠肾损伤的作用机制。方法：大鼠 分为假手术组、脓毒症大鼠模型组（ 模型组）、转染miR-494 inhibitor 脓毒症大鼠模型组（miR-494 inhibitor 组）。Masson 三色法检测大鼠肾组织病变程度,ELISA 法检测炎症因子水平,免疫印迹检测NF-κB 的蛋白表达, TUNEL 检测肾小管细胞凋亡,全自动生化分析仪检测大鼠血清及尿液中血肌酐（Scr）、尿素氮（BUN）及24 h 尿蛋白定量（UTP）等生物化学指标。结果：与假手术组相比,模型组及miR-494 inhibitor 组大鼠肾组织中miR- 494 表达量均升高,但miR-494 inhibitor 组大鼠miR-494 表达低于模型组;模型组和miR-494 inhibitor 组大鼠血清 中Scr、BUN 和UTP的表达水平均显著升高。与模型组相比,miR-494 inhibitor 组大鼠血清Scr、BUN、UTP水 平显著降低。假手术组肾组织结构完整,miR-494 inhibitor 组肾小球间质增多,肾间质增宽,炎症细胞浸润严重。 与miR-494 inhibitor 组相比,模型组肾小球硬度增加,肾小管周围组织炎症细胞浸润更加严重。假手术组大鼠白 介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和IL-1β 的表达水平最低,模型组大鼠IL-6、TNF-α 和IL-1β 的表达最高; 与模型组比较,miR-494 inhibitor 组大鼠IL-6、TNF-α 和IL-1β 的水平明显降低,肾小管上皮细胞的凋亡率比模型 组低,但高于假手术组。miR-494 inhibitor 组中大鼠NF-κB p65 蛋白表达比模型组低,但高于假手术组。结论： miR-494 低表达可抑制脓毒症大鼠NF-κB p65 的表达,降低炎症因子水平,从而改善肾损伤程度。     

外周血miR-494及Let-7e在诊断急性缺血性脑卒中患者中的临床价值

目的：通过检测急性缺血性脑卒中患者与正常对照组外周血中miR-494及Let-7e的表达水平,探讨其与急性缺血性脑卒中的关系。方法：收集67例急性缺血性脑卒中患者及50例非卒中正常健康人群,采用实时荧光定量PCR法(Quantitative Real-time PCR,QRT-PCR)检测血浆中miR-494及Let-7e表达水平,比较两组外周血中表达水平的差异。并对miR-494及Let-7e行ROC曲线分析,分析其对急性缺血性脑卒中的诊断价值。进一步将急性缺血性脑卒中患者分为预后不佳组(MRS 3-6)和预后良好组(MRS0-2),分析其在两组之间的差异。结果：急性缺血性脑卒中患者外周血中的miR-494(1.71±1.14)及Let-7e(1.43±0.93)的表达水平较正常对照组外周血明显升高(P<0.05)。miR-494及Let-7eROC曲线下面积分别为0.777、0.756。预后不良组的miR-494(2.04±0.11 vs.1.46±0.05)及Let-7e(1.68±0.61 vs.1.24±0.27)表达水平均较预后良好组显著升高,两组之间有统计学差异(P<0.05)。结论：miR-494及Let-7e可能与急性缺血性脑卒中相关,对急性缺血性脑卒中患者的临床诊断和预后判断具有潜在的应用价值。     

MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40

PurposeCerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species (ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40) in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion (I/R) injury.Materials and MethodsA mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemia in vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation (OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. The relationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays.ResultsBhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40 overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p was verified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reverse the effects of miR-494-3p overexpression on ROS production and cell apoptosis.ConclusionMiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.     

miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer

Altered microRNA (miRNA) expression may occur early in bladder cancer and may play a role in carcinogenesis and tumor behavior. We evaluated whether alterations in miRNA expression could improve disease stratification and outcome prognosis in bladder tumors and noninvasive diagnosis in urinary samples. miR-143, miR-222, and miR-452 expression levels were analyzed by quantitative RT-PCR (RT-qPCR) in paired urinary and matching tumors and in two independent prospective series of tumors and urinary specimens. Differential expression of miR-143, miR-222, and miR-452 in urine were verified by in situ hybridization in matching tumors. Tumor miRNA expression by RT-qPCR correlated with tumor grade, size, and presence of carcinoma in situ for miR-222, recurrence (miR-222 and miR-143), progression (miR-222 and miR-143), disease-specific survival (miR-222), and overall survival (miR-222). Protein expression patterns of potential miRNA targets, including vascular endothelial growth factor, BCL2, v-erb-b2 erythroblastic leukemia viral oncogene (ERBB) homolog 3, and ERBB4, were evaluated by IHC in tissue arrays containing tumors for which miRNAs were assessed by RT-qPCR. Target expression correlated with expression of their predicted regulatory miRNAs, recurrence (ERBB3), progression (ERBB4), disease-specific survival (ERBB3 and ERBB4), and overall survival (ERBB3 and ERBB4). Furthermore, RT-qPCR of miR-452 (area under the curve, 0.848) and miR-222 (area under the curve, 0.718) in urine provided high accuracies for bladder cancer diagnosis. Thus, bladder tumors were characterized by changes in miRNA expression that could aid in tumor stratification and clinical outcome prognosis, and miRNAs were detected in urinary specimens for noninvasive diagnosis.     

Expression of P-glycoprotein in hepatocellular carcinoma. A determinant of chemotherapy response

To characterize the P-glycoprotein (Pgp) expression in human hepatocellular carcinoma (HCC), we studied 101 cases of HCC treated with surgical resection without prior treatment. Pgp expression was detected immunohistochemically using 2 monoclonal antibodies (C494, C219) and correlated with pathologic features, survival, and p53 expression. Chemotherapy response was analyzed in a separate group of patients with inoperable HCC treated with systemic chemotherapy. Positive immunostaining was seen in 92% and 80% of the tumors with C494 and C219, respectively; bile canalicular type staining was seen in all positive tumors. Pgp expression was less extensive in the tumors than in the corresponding nontumorous liver tissue. Tumor Pgp expression with either antibody had no association with cellular differentiation, aggressive pathologic features, survival, or p53 overexpression. In patients with inoperable HCC, the chemotherapy response was significantly inversely related to Pgp expression with C494 and C219. Pgp was expressed in human HCC but was patchy and less extensive than in the nontumorous tissue. Response to systemic chemotherapy was inversely related to the level of Pgp expression in patients with inoperable tumors. Pgp expression in tumors not treated with chemotherapy was not associated with a more aggressive tumor phenotype or p53 overexpression and did not influence survival.     

Gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas

BackgroundBreast carcinoma is one of the most common tumors in women. The immune microenvironment, especially T cell infiltration, is related to the occurrence and prognosis of breast carcinoma.ObjectiveThis study investigated the gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas.MethodsThe gene expression data and corresponding clinical phenotype data from the Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) were downloaded. The stromal and immune score were calculated using ESTIMATE. The differentially expressed genes (DEGs) with a high vs. low stromal score and a high vs. low immune score were screened and then functionally enriched. The tumor-infiltrating immune cells were investigated using the Cibersort algorithm, and the CD4+ and CD8+ T cell-related genes were identified using a Spearman correlation test of infiltrating abundance with the DEGs. Moreover, the miRNA-mRNA pairs and lncRNA-miRNA pairs were predicted to construct the competing endogenous RNAs (ceRNA) network. Kaplan-Meier (K-M) survival curves were also plotted.ResultsIn total, 478 DEGs with a high vs. low stromal score and 796 DEGs with a high vs. low immune score were identified. In addition, 39 CD4+ T cell-related genes and 78 CD8+ T cell-related genes were identified; of these, 14 genes were significantly associated with the prognosis of BRCA patients. Moreover, for CD4+ T cell-related genes, the chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis was identified from the ceRNA network, whereas the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis was identified for CD8+ T cell-related genes.ConclusionsThe chr22-38_28785274-29006793.1–miR-34a/c-5p–CAPN6 axis and the chr22-38_28785274-29006793.1–miR-494-3p–SLC9A7 axis might regulate cellular activities associated with CD4+ and CD8+ T cell infiltration, respectively, in BRCA.     

miR-132在神经系统疾病中作用的研究进展

MicroRNAs(miRNAs)作为基因表达的关键调控因子,主要通过在转录后调控大量靶信使RNA(messenger RNA,mRNA)的表达,参与大部分生物学过程以及许多疾病的发病机制。miR-132的表达在神经元发育、成熟过程中是必要的。同时,miR-132作为一种最重要的神经相关miRNAs之一,在神经系统和免...     

Participation of miR-200 in pulmonary fibrosis

Excessive extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF). Epithelial-mesenchymal transition, involving transition of alveolar epithelial cells (AECs) to pulmonary fibroblasts, appears to be an important contributory process to lung fibrosis. Although aberrant expression of microRNAs (miRs) is involved in a variety of pathophysiologic processes, the role of miRs in fibrotic lung diseases is less well understood. In the present study, we found that miR-200a, miR-200b, and miR-200c are significantly down-regulated in the lungs of mice with experimental lung fibrosis. Levels of miR-200a and miR-200c were reduced in the lungs of patients with IPF. miR-200 had greater expression in AECs than in lung fibroblasts, and AECs from mice with experimental pulmonary fibrosis had diminished expression of miR-200. We found that the miR-200 family members inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition of AECs. miR-200 family members can reverse the fibrogenic activity of pulmonary fibroblasts from mice with experimental pulmonary fibrosis and from patients with IPF. Indeed, the introduction of miR-200c diminishes experimental pulmonary fibrosis in mice. Thus, the miR-200 family members participate importantly in fibrotic lung diseases and suggest that restoring miR-200 expression in the lungs may represent a novel therapeutic approach in treating pulmonary fibrotic diseases.