miR-26b-3p靶向调控TRA2B表达抑制神经胶质瘤细胞的增殖和转移

目的探讨miR-26b-3p在神经胶质瘤细胞中的表达,以及其对神经胶质瘤细胞增殖和转移的影响。方法采用荧光实时定量PCR(qRT-PCR)检测神经胶质瘤组织与癌旁组织中miR-26b-3p与TRA2B的表达水平;通过向神经胶质瘤细胞细胞系中转染miR-26b-3p mimic和inhibitor干扰内源miR-26b-3p的表达,同时检测其靶基因TRA2B蛋白的表达变化;采用CCK-8法检测各组神经胶质瘤细胞增殖能力的变化,以及划痕实验对癌细胞迁移能力进行评估。结果神经胶质瘤患者组织与癌旁组织比较,miR-26b-3p的表达水平显著上调,TRA2B的表达水平显著下降,差异有统计学意义(P<0.05);Pearson相关性分析显示,在32例神经胶质瘤患者神经胶质瘤组织中,TRA2B的表达水平与miR-26b-3p表达呈显著负相关(r=-0.510;P<0.05);SHG-44细胞体外转染实验结果发现,降低细胞内源miR-26b-3p的表达时,TRA2B的表达水平显著升高,细胞的增殖活性以及转移能力会被抑制;而上调细胞内源miR-26b-3p的表达时,TRA2B的表达水平显著下降,细胞的增殖活性与转移能力会显著提高,相比于对照组,差异有统计学意义(P<0.05)。结论 miR-26b-3p在神经胶质瘤组织中高表达,其可能靶向调控TRA2B的表达抑制神经胶质瘤细胞的增殖活性与转移能力,在神经胶质瘤的发生发展过程中起着重要的生理功能。     

miR-195 inhibits tumor growth and angiogenesis through modulating IRS1 in breast cancer

Angiogenesis has been found as an attractive target for drug therapy as it is necessary for tumor growth. Accumulating evidences show that microRNAs (miRNAs), which are a group of highly conserved, single-stranded, short non-coding RNAs, play important roles through directly targeting angiogenic factors and protein kinases. The purpose of this study is to investigate the role of miR-195 in breast cancer development and angiogenesis through targeting IRS1. We show that miR-195 is inversely related with Insulin receptor substrate 1 (IRS1) in both breast cancer cells and breast cancer tissues. Induction of miR-195 could suppress IRS1 protein expression through binding to its 3′UTR regions either by transfection with miR-195 oligo or by infection with lentivirus encoding miR-195 gene. Moreover, re-expression of IRS1 reverses miR-195-mediated repression of tumor cell growth and miR-195 inhibits tumor angiogenesis through suppressing IRS1-VEGF axis. These data suggest that miR-195 mimics are potential therapeutic agents for breast cancer diagnose.     

肝硬化患者血清miR-122的表达及与Child-Pugh分级的关系

目的探讨肝硬化患者血清MicroRNA(miR)-122的表达水平与肝硬化Child-Pugh分级及并发症的关系。方法肝硬化患者87例,采用PCR实时荧光定量法测定患者血清miR-122水平,根据Child-Pugh分级对肝硬化患者进行分级,分析血清miR-122与肝硬化分级的关系。结果并发肝硬化腹水、消化道出血、自发性细菌性腹膜炎及失代偿期患者血清miR-122表达水平均高于未发生患者(P<0.05);不同肝硬化Child-Pugh分级血清中miR-122水平有统计学差异(P<0.05),A级与B级肝硬化患者血清miR-122水平无显著差异(P>0.05),A级和B级患者水平均显著低于C级(P<0.05)。多变量线性相关性显示,血清miR-122与丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(GGT)、碱性磷酸酶(ALP)呈正相关(P<0.05);与国际标准化比值(INR)及肌酐(Cr)水平呈负相关(P<0.05)。结论血清miR-122水平上升提示肝硬化已经失代偿,并与腹水、消化道出血、肝肾衰竭有关。因此,血清miR-122可作为评价肝硬化患者肝脏功能及预后的潜在生物学指标。     

miR-7在肾癌中的表达及临床意义研究

目的检测肾细胞癌组织及相应癌旁正常组织中miR-7的表达,分析18达与临床病理特征之间的关系,为进一步研究miR-7在肾癌的发生发展中作用奠定基础。方法收集48例经手术切除的配对肾癌及癌旁组织标本,提取组织中总RNA,经逆转录获得cDNA,采用实时荧光定量PCR（RT-qPCR）方法检测标本中miR-7表达量,并通过统计学软件分析其表达量与患者临床病理特征之间的相关性。结果与相应癌旁组织相比,肾癌组织中miR-7表达量明显升高,其中34例（70.8%）肾癌标本miR-7表达上调,14例（29.2%）表达下调,差异有统计学意义（P〈0.05）。肾细胞癌中miR-7表达上调与患者年龄、性别、肾癌组织类型、TNM分期、AJCC临床分期无相关性（P〉0.05）。结论 miR-7在肾癌组织中明显高表达,提示其可能与肾癌的发生和发展相关,可能成为肾癌早期诊断、治疗乃至预后判断的新的生物标记物。     

Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR)

Objective: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin (ATTR) amyloidosis.

Patients and methods: We performed a retrospective analysis of patients with biopsy-proven ATTRwt (wild-type transthyretin amyloid protein) and genopositive ATTR V122I (valine-to-isoleucine substitution at position 122 of the TTR gene) amyloidosis evaluated at the Amyloidosis Center at Boston University and Boston Medical Center between 1 January 2003 and 31 December 2016.

Results: There were a total of 226 patients with ATTRwt and ATTR V122I amyloidosis evaluated during the specified time frame with 155 and 71 patients in each cohort, respectively. Those with complete medical records, 140 patients with ATTRwt and 57 V1221 ATTRm subjects, were included in the analyses. Fifty-five patients (39%) in the ATTRwt cohort and 28 patients (49%) in the ATTR V122I cohort had an MGUS, as indicated by an abnormality in the serum-free light-chain ratio and/or serum immunofixation electrophoresis.

Conclusion: These data confirm the high prevalence of coexistent MGUS with ATTR amyloidosis in this patient population, with an MGUS rate that is higher than the general population. These findings also highlight the importance of a thorough diagnostic evaluation in patients with amyloidosis to determine the precursor protein, as the clinical course and treatment of AL (light-chain amyloid protein) and ATTR amyloidosis are distinct.     

Low Prevalence of Clinically Apparent Cardiac Amyloidosis Among Carriers of Transthyretin V122I Variant in a Large Electronic Medical Record

BackgroundTransthyretin (TTR) gene mutations are the most common cause of hereditary amyloidosis. Valine replaced by isoleucine in position 122 (V122I) variant is common, particularly in the black population. Carriers of V122I have increased risk for developing cardiac amyloidosis. Despite a relatively high prevalence, the penetrance of V122I is not firmly established. This study sought to determine the prevalence of clinically apparent cardiac amyloidosis among carriers of the TTR V122I variant.MethodsBioVU, a Vanderbilt University resource linking DNA samples and pre-existing genetic data to de-identified electronic medical records was used to identify TTR V122I mutation carriers. Automated billing code queries (International Classification of Diseases, 9th revision codes), problem list searches, and manual chart reviews were used to identify subjects with clinically diagnosed cardiac amyloidosis.ResultsAmong 28,429 subjects with available genotype data, 129 were V122I carriers. Carriers had a median age of 42 years (interquartile range 16-64). Noncarriers had a median age of 62 years, (interquartile range 41-77). The carrier rate was 3.7% in blacks and 0.02% in whites. Overall, the prevalence of clinically apparent cardiac amyloidosis was 0.8% in carriers and 0.04% in noncarriers (P = .05). Above age 60, the prevalence of cardiac amyloidosis was 2.6% in carriers and 0.06% in noncarriers (P = .03).ConclusionCarriers of the TTR V122I variant are at a higher risk for development of cardiac amyloidosis, particularly at age>60 years. However, clinically apparent cardiac amyloidosis in this population was uncommon. These results support that the penetrance of TTR V122I is age dependent and suggest it may be significantly lower than previously reported.     

姜黄素下调miR-155抑制缺血性脑卒中炎性应答的实验研究

目的分析姜黄素对缺血性脑卒中的抗炎作用,并探讨miR-155、Toll样受体4(TLR4信号通路是否参与该抗炎机制。方法线栓法建立Sprague Dawley大鼠大脑中动脉闭塞模型(MCAO),将大鼠分为假手术组(8例)、MCAO模型组(8例)、姜黄素治疗组(8例),检测大鼠梗死体积、miR-155 mRNA相对表达量以及TLR4蛋白表达情况,ELISA法检测大鼠肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)表达。结果姜黄素显著改善MCAO大鼠脑梗死体积、神经系统功能评分以及运动功能(P<0.05),可显著降低MCAO大鼠miR-155mRNA、TLR4蛋白以及炎性因子TNF-α、IL-6、IL-1β的表达(均P<0.05)。结论姜黄素主要通过下调miR-155/TLR4信号通路抑制缺血性脑卒中的炎性应答。     

MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.