PAQR3: a novel tumor suppressor gene

PAQR3, also known as RKTG (Raf kinase trapping to Golgi), is a member of the progestin and adipoQ receptor (PAQR) family. The role of PAQR3 as a tumor suppressor has recently been established in different types of human cancer in which PAQR3 exerts its biological function through negative regulation of the oncogenic Raf/MEK/ERK signaling. Multiple studies have found that PAQR3 downregulation frequently occurs in human cancers and is very often associated with tumor progression and shortened patients’ survival. Moreover, restoring the expression of PAQR3 could induce apoptosis and inhibit proliferation and invasiveness of cancer cells. Downregulation of PAQR3 by oncogenic microRNAs has also been reported. In this review, we summarized current knowledge concerning the role of PAQR3 in tumor development. To our knowledge, this is the first review on the role of this novel tumor suppressor.     

Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers

miRNA expression is deregulated in non-small cell lung cancer (NSCLC), and some miRNAs are associated with gefitinib sensitivity. Here, we investigated if circulating miRNAs could be a useful biomarker for the prediction of EGFR mutation and the patient’s prognosis. The differential miRNAs related to gefitinib sensitivity were screened and identified by microRNA array. Using Taqman-based real-time RT-PCR, we analyzed the expression of selected miRNAs in tumor tissues and plasma of 150 NSCLC patients. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to determine the association between miRNAs expression and survival. Receiver operating characteristic curve analysis was also performed. Compared with PC9 cell line, 41 microRNAs detected by microarray were significantly differentially expressed in A549 and H1299 cells. The 5 selected hsa-miRNAs were all found differently expressed between wild and mutant EGFR carriers (all P<0.01). Down-regulation of 5 selected miRNAs were independently associated with lymphatic invasion (all P<0.01) and clinical stage (all P<0.01), respectively. Both down-regulation of has-miR-195 (P=0.012) and has-miR-21 (P=0.004) were associated with poor differentiation. All up-regulation of 5 has-miRNAs were associated with smoking (All P<0.05). 5 hsa-miRNAs were up-regulated both in plasma and tissue samples. A model including 4 hsa-miRNAs may predict EGFR mutational status and gefitinib-sensitivity (both AUC: 0.869). Plasma levels of has-miR-125b expression were associated with disease-free survival (P=0.033) and overall survival in the patients (P=0.028). In a word, Circulating 5 selected miRNAs may especially be useful in predicting EGFR mutation, and circulating hsa-miR-125b may have prognostic values in NSCLC patients.     

血清miR-146a／b实时荧光定量分析及其作为分子标志物的初步评价

目的：以特异性调节Toll样受体信号通路的miR-146a／b为检测靶标,建立血清miRNAs分子荧光定量检测方法,并对其作为血清炎症分子标志物的潜在价值进行初步评价。方法：采集正常体质量儿童血清20例（对照组）、超重儿童血清20例（超重组）、肥胖儿童血清20例（肥胖组）及健康成年人血清50例（健康成人组）,酚-氯仿法提取血清总RNAs,SYBRGreen实时荧光定量技术定量检测血清中miR-146a／b拷贝数,GraphpadPrism5．0软件进行统计分析并绘图。结果：对照组血清中miR-146a的拷贝数显著低于超重组（P=-0．0061）和肥胖组（P=-0．0262）,超重组和肥胖组之间差异无统计学意义（P=0．0656）。miR-146a表达量的受试者工作特征曲线下面积（AUC）分析显示：对照组vs超重组AUC=O．8475,P=-0．0002;对照组vs肥胖组AUC=0．6050,P=-0．2560;超重组vs肥胖组AUC=0．5475,P=0．6073。miR-146b与miR-146a呈不同表达趋势,超重组儿童血清miR-146b拷贝数显著高于对照组（P=-0．0090）和肥胖组儿童（P=0．0023）,肥胖组儿童血清中miR-146b的拷贝数均值虽略低于对照组,但差异无统计学意义（P=-0．1556）。miR-146b表达量的AUC分析显示：正常组vs超重组AUC=0．7425,P=O．0087;正常组vs肥胖组AUC=0．6325,P=0．1517;超重组vs肥胖组AUC=0．7825,P=0．0023。miR．146a／b拷贝数值变异系数（CV）大：对照组、超重组和肥胖组儿童血清中miR。146a拷贝数的cv值分别为80．94％、110．94％、175．88％;miR-146b拷贝数的cV值分别为164．11％、189．72％、152．00％。在健康成人血清中miR-146a／b呈现相近表达模式,miR-146a和miR-146b的cV值分别是37．86％、74．82％。结论：miR-146a在对照组、超重组和肥胖组的表达量变化显示其与儿童肥胖具有-定相关性,可以从整体水平说明miR-146a与体内炎症水平呈正相关关系,但是由于其在血清中拷贝数值变异较大且各组问无明确分界,不能确定其参考值范围。因此,血清miR-146a／b拷贝数差异不足以用于临床个体化诊断,血清miR-146a／b作为炎症相关分子标志物的价值尚需进一步探讨。     

Expression profiles of miRNAs in human pancreatic cancer cell lines

Objective： To analyze initially the differences of miRNAs expression profiles in human pancreatic cancer cell lines by microarray technique. Methods： A total of 743 probes were designed according to the known miRNAs sequences of human, mice, and rats. miRNAs microarray was manufactured and its credibility was verified. Total RNAs were extracted and miRNAs were separated from human pancreatic cancer cell lines （SW1990, Capan-2, BxPC-3, Aspc-1, and Pancl） and immortal human pancreatic duct epithelial cell line H6C7. They were labeled with T4 RNA ligase, then were hybridized with microarray. Through array scan and analysis, miRNAs expression profiles in pancreatic cancer were obtained. The results were verified by Northern blotting and RT-PCR. Results： A total of 63 rniRNAs related to pancreatic cancer were found to be differentially expressed in 5 pancreatic cancer cell lines, including 25 down-regulated and 38 up-regulated miRNAs. Expressions of mir-21 and let-7 were also confirmed： Conclusion： The results suggested that miRNAs expression profiles could be found in pancreatic cancer cells.     

miRNAs与肿瘤血管形成

血管形成是机体一种极其重要的生理过程,它不仅涉及组织再生和创伤愈合,还涉及多种病理过程,如肿瘤的生长与侵袭。在1972年,美国学者Folkman首次提出肿瘤的生长取决于血管形成,正是如此,它使得肿瘤发生转移和无限制生长。miRNA是小的非编码RNA,它作为分子开关调控肿瘤的血管形成,研究表明,miRNA在内皮细胞生物学和肿瘤血管形成方面起着重要的作用,本篇综述将阐述miRNA在肿瘤血管形成中的作用及治疗上的进展。     

急性冠脉综合征患者循环miR-208b-3p与心室重构的关系研究

目的 探究急性冠脉综合征患者循环miR-208b-3p表达水平与心室重构的关系。方法 收集140例西安市第九医院心血管内科2015年11月至2016年12月确诊为急性冠脉综合征患者,实时定量PCR（quantification PCR,qPCR）检测样本miR-208b-3p的表达水平,根据miR-208b-3p表达水平高低以每组同样患者数分为四组,分别比较四组住院及出院1年随访超声测量结果,并对测量值变化率做进一步对比分析。结果 住院期间各超声测量组患者例数之间差异无统计学意义（p>0.05）,出院1年各左心室舒张末期内径（left ventricular end-diastolic dimension,LVDd）组和各左心室射血分数（left ventricular ejection fraction,LVEF）组患者例数的差异具有统计学意义（p=0.046;p=0.036）,各左心室短轴缩短率（fraction shortening,FS）组差异无统计学意义（p>0.05）。变化率分析显示各组LVDd变化率分别为（-0.410±0.125、0.024±0.156、0.082±0.152、0.004±0.078）（p=0.326）;各组FS变化率分别为（0.081±0.379、0.074±0.209、0.061±0.258、0.123±0.310）（p=0.896）;各组LVEF变化率分别为（0.082±0.035、0.046±0.035、0.022±0.037、-0.082±0.052）（p=0.034）。对各组LVEF测量值变化率进行两两对比显示高危组分别与低危组及中低危组差异具有统计学意义（p=0.010;p=0.042）。结论 循环miR-208b-3p与远期心室重构相关,并且对LVEF值的影响最大。     

miRNAs在2型糖尿病发病中的作用

2型糖尿病是一个严重的、全球性的慢性疾病,遗传和环境等因素的改变可导致2型糖尿病的发生.尽管胰岛素抵抗(insulin resistance,IR)被认为贯穿2型糖尿病发生、发展的全过程,但其形成的主要病理机制还不十分清楚.微小RNA(miRNAs)是一类内源性非蛋白编码的长度约为20～25 nt的小分子RNA,能在转录后水平调节基因的表达.近年来研究发现miRNAs参与生命过程中一系列的重要进程,如个体发育、器官形成、细胞分化、增殖与凋亡等生物学过程.特别是近年发现miRNAs参与2型糖尿病发生发展的调节.