MiR-106a 在子宫内膜癌中的表达及意义

目的  检测miR-106a 在子宫内膜癌、不典型增生及正常子宫内膜组织中的表达,探讨它们与子宫内膜癌发生、 发展、侵袭和转移的关系。方法  收集40例子宫内膜癌患者、20例子宫内膜不典型增生患者及30例子宫内膜正常的患者（包 括异常子宫出血及子宫肌瘤患者）的组织标本,应用poly（A）-RT-qPCR 技术,检测miR-106a 在三种不同子宫内膜组织 中的表达,并分别将检测结果和子宫内膜癌患者的临床及病理资料进行统计学分析。结果  miR-106a 在子宫内膜癌、不典 型增生及正常子宫内膜组织中的相对表达量分别为0.667（0.197,1.624）,0.245（0.064,0.759）和 0.104（0.003,1.350）, 表达量逐渐下降,3组间差异有统计学意义（P＜0.01）,子宫内膜癌组织中miR-106a的表达显著高于正常子宫内膜组织（P ＜ 0.01）,同时高于不典型增生组织（P ＜ 0.05）,而不典型增生与正常子宫内膜组织相比较,其差异无统计学意义（P ＞0.05）;miR-106a在Ⅲ+Ⅳ期子宫内膜癌患者中的表达量高于Ⅰ+Ⅱ期;有淋巴结转移的患者中的表达量高于无转移者, 差异均有统计学意义（P ＜ 0.05）;不同年龄、病理类型、病理分级、肌层浸润深度及ER、PR 是否阳性子宫内膜癌患者 中其表达量的差异无统计学意义（P ＞ 0.05）。结论  miR-106a 在子宫内膜癌组织中高表达,可能作为癌基因调控子宫内 膜癌的发生及发展。     

增生性玻璃体视网膜病变中水通道蛋白-1表达的实验研究

目的　检测水通道蛋白-１（ａｑｕａｐｏｒｉｎ-１,ＡＱＰ-１）在增生性玻璃体视网膜病变（ｐｒｏ-ｌｉｆｅｒａｔｉｖｅｖｉｔｒｅｏｒｅｔｉｎｏｐａｔｈｙ,ＰＶＲ）中的表达,以确定其在ＰＶＲ细胞迁移和增殖中可能的作用。方法　从１０例ＰＶＲ患者的眼科手术中收集１０例ＰＶＲ增生膜。采用实时定量聚合酶链反应（ＲＴ-ｑＰＣＲ）和免疫荧光法分别确定ＰＶＲ增生膜中ＡＱＰ-１ｍＲＮＡ和蛋白的表达。结果　ＲＴ-ｑＰＣＲ检测发现,ＡＱＰ-１ｍＲＮＡ在所有ＰＶＲ增生膜中均出现了显著表达,其扩增的Ｃｑ值为２７～２９（２８．１０±０．５４）;免疫荧光检测发现,ＡＱＰ-１标记细胞所总细胞数的比例为（２５．３６ ±２．３５）％,且ＡＱＰ-１蛋白主要表达在增生膜的边缘细胞中。同时１０例ＰＶＲ增生膜ＡＱＰ-１ｍＲＮＡ和蛋白质的表达非常接近,并无明显差别,与患者年龄、性别和之前是否接受过手术等无关。结论　ＡＱＰ-１可能在ＰＶＲ细胞迁移和增殖过程中起到了潜在的作用。     

Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration-response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies.     

组织与脱落细胞中的microRNA表达量检测指示miR-203在口腔扁平苔藓中的潜在作用

口腔扁平苔藓（OLP）是一种癌前病变和慢性炎症,其损伤具有组织学异质性,多种类型的细胞参与其发生与恶性转化,而其分子机制尚不明确。本研究检测了来自于OLP患者和健康志愿者口腔组织和脱落细胞中miR。96／182／183簇、miR-203、miR-375、miR-769—5p的表达水平,并通过双标图法评价了显著差异表达的miRNA与OLP的相关性。研究发现。相对于志愿者正常组织,miR．203在患者病损区组织中显著高表达,其变化程度明显高于其它miRNA。与此相反,miR-203及miR-96／182／183簇的表达在脱落细胞中则没有显著差异,提示OLP病损区中不同类型细胞对miRNA表达的调控不同,可能与OLP的组织学异质性相关。双标图分析表明miR-203与miR-96／182／183簇的表达量在患者病损区组织中呈正相关。本研究结果表NmiR-203不仅在分子层次显示TOLP的组织学异质性,还可能成为潜在的诊断标志物和治疗药物靶标。     

Expression and clinicopathological significance of miR-146a in hepatocellular carcinoma tissues

Background. Aberrant expression of microRNA-146a (miR-146a) has been found in several classes of cancers. However, its expression and clinicopathological contribution in hepatocellular carcinoma (HCC) has not been fully elucidated.

Objective. To explore the clinicopathological significance of the miR-146a level in HCC formalin-fixed paraffin-embedded (FFPE) tissue.

Methods. Eighty-five HCC samples and their para-cancerous normal liver tissues were collected. Total mRNA including miRNA was extracted, and miR-146a expression was determined using real-time RT-PCR. Furthermore, the correlation between the miR-146a expression and clinicopathological parameters was investigated.

Results. MicroRNA-146a expression in HCC tissues was lower compared with that in adjacent non-cancerous hepatic tissues. MicroRNA-146a expression was also related to clinical TNM stage, metastasis, portal vein tumor embolus, and number of tumor nodes.

Conclusions. Down-regulation of miR-146a is related to HCC carcinogenesis and deterioration of HCC. MicroRNA-146a may act as a suppressor miRNA of HCC, and it is therefore a potential prognostic biomarker for HCC patients.