化疗耐药及敏感卵巢癌细胞差异表达microRNA的筛查与组织鉴定

Screening of Differentially Expressed microRNA in Chemoresistant and Sensitive Ovarian Cancer Cells and the Identification of the Tissues

目的探讨microRNA在卵巢浆液性癌化疗耐药及敏感组织的差异表达，为卵巢浆液性癌化疗耐药的研究提供理论依据。方法应用microRNA表达谱基因芯片，研究紫杉醇耐药卵巢癌细胞skov3-tr30及其敏感细胞skov3基因表达谱，获得表达差异的microRNA后，选取部分差异表达的microRNA用实时聚合酶链反应对化疗耐药与敏感卵巢浆液性癌组织各20例进行验证。结果通过microRNA表达谱基因芯片方法筛选出171个与卵巢癌细胞化疗耐药相关microRNA，基因表达增高（上调趋势）69个，为miR-17、miR-19b、miR-92—1、miR-210、miR-1307等；基因表达降低（下调趋势）102个，为miR—134、miR-34、miR一196b等。miR-17～92是与卵巢癌耐药最相关的microRNA之一。miR—17～92基因簇在化疗耐药卵巢浆液性癌组织中表达水平显著高于敏感组织，差异有统计学意义（P〈0．01）。miR-17～92基因簇表达与卵巢浆液性癌及化疗耐药卵巢浆液性癌患者绝经前后、手术病理分期、组织学分级、是否行淋巴结清扫术和有无淋巴结转移均无明显相关性（均P〉0．05）。结论microRNA表达谱基因芯片可筛查出化疗耐药及敏感卵巢癌细胞的差异表达基因，miR-17～92基因簇与卵巢浆液性癌化疗耐药有关。

Objective To explore the different expression profiles of microRNA in ovalian serous cancer tissue with both chemoresistant and sensitive status, for a better understanding of chemoresistance in the mechanism of chemoresistance in ovaliml serous cancer. Methods The expression of mieroRNA was evaluated by mieroRNA microarray in the human ovarian carcinoma skov3 cells and paclitaxel resistant skov3-tr30 cells. Tile differently expressed microRNA was selected for further verification of the selected microRNA in 20 pairs of chemore- sistant mad sensitive ovarian serous cancer tissues. Results A total of 171 mieroRNA related to chemoresistant ovarian cancer cells were, selected by microarray,in which 69 microRNA （miR-17,miR-19b,nfiR-92-1,miR-210,miR-1307,etc.） were up-regulated while 102 mi- croRNA （nfiR-134, miR-34, miR-196b, etc. ） were down-regulated in skov3-tr30 cells, miR-17-92 was one of the microRNA which hmt good correlation with ovarian carcinoma chemoresistance. Chemoresistant ovarian serous cancer expressed obviously higher level of miR-17-92 clus- ter than the chemosensifive tissue, with a good s ＇tatistical significance （ P 〈 0.01 ）. In ovarian serous cancer and the ehemoresistance of o- varian serous cancer, there was no obvious correlation between expression of miR-17-92 cluster and factors of biological behaviors before and ＇after menopause, smgical pathologic stage, histological grade, lymph node dissection, and lymph node metastasis （ P 〉 0.05 ）. Conclu- sion mieroRNA mieroarray is a valid method to screen differentially expressed nfieroRNA, miR-17-92 could be a causal factor to the chemoresistanee of ovarian serous cancer. This study provides a theoretical basis for the research of ovarian serous cancer chemoresistance.