肿瘤防治研究2013,Vol.40Issue(7):660-666,7.DOI:10.3971/j.issn.1000-8578.2013.07.008
miR-107靶向调控Dicer1促进卵巢癌细胞系侵袭转移
MicroRNA-107 Targeting Dicer1 for Metastasis Control in Ovarian Cancer Cell Lines
摘要
Abstract
Objective To explore the expression level of MicroRNA-107 (miR-107) in ovarian cancer,so as to figure out the mechanism involved in invasion and metastasis control of ovarian cancer cell lines for miR-107.Methods By comparison miR-107 expression levels in ovarian cancer and normal ovarian tissues,or between normal ovarian surface epithelium and ovarian cancer cell lines by qRT-PCR,we confirmed the differential expression and then predicted Dicer1 as its specific validated target gene with the approach of bioinformatics.Furthermore,the dual luciferase reporter system was adopted to verify the prediction.After elevating miR-107 level,Western blot was performed to detect the protein level of Dicer1 ; scratch test and transwell assay were employed to check the alteration of movements,invasion and metastasis in ovarian cancer cell line SKOV3; furthermore,qRT-PCR and Confocal were applied to study the level of EMT associated molecular,such as E-cadherin,β-Catenin,N-cadherin,Vimentin,Fibronectin,ICAM-1,and MMP-9 respectively.Results The expression level of miR-107 in epithelial ovarian carcinoma was increased when compared with that of normal tissues (P<0.05).The dual luciferase reporter system validated Dicer1 as a specific target gene of miR-107.Dramatically reduction of Dicer1 was observed with miR-107 overexpression,at the same time,morphological change occured and cell invasion and metastasis ability increased a lot due to the upregulation of mesenchymal molecules,including β-Catenin,N-cadherin,MMP-9 following miR-107 upregulated.Conclusion miR-107,acting as an oncogene miRNA,promoted invasion and metastasis via downregulation of miRNA regulatory machinery Dicer1 and mediated EMT process in ovarian cancer.Inhibition of miR-107 or restoration of Dicer1 may represent a new potential therapeutic target for ovarian cancer treatment.关键词
卵巢癌/微小RNA-107/Dicer1/上皮间质转化Key words
Ovarian cancer/ MiR-107/ Dicer1/ EMT分类
医药卫生引用本文复制引用
杨宗元,孙朝阳,周波,李娜,何扬,丁冬,陈刚,朱涛..miR-107靶向调控Dicer1促进卵巢癌细胞系侵袭转移[J].肿瘤防治研究,2013,40(7):660-666,7.基金项目
中央高校基本科研业务基金资助项目(HUST:2012TS058) (HUST:2012TS058)
国家青年基金资助项目(30801340/H1608,81000979/H1609) (30801340/H1608,81000979/H1609)
湖北省自然科学基金资助项目(2011CBD542) (2011CBD542)