MicroRNA-18a inhibits ovarian cancer growth via directly targeting TRIAP1 and IPMK

被引:35
|
作者
Liu, Ping [1 ]
Qi, Xiaorong [1 ]
Bian, Ce [1 ]
Yang, Fan [1 ]
Lin, Xiaojuan [1 ]
Zhou, Shengtao [1 ]
Xie, Chuan [1 ]
Zhao, Xia [1 ,2 ,3 ]
Yi, Tao [1 ,2 ,3 ]
机构
[1] Sichuan Univ, West China Hosp 2, Dept Gynecol & Obstet,Minist Educ, Key Lab Birth Defects & Related Dis Women & Child, 20,Sect 3,South Peoples Rd, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China
关键词
epithelial ovarian cancer; microRNA-18a; TRIAP1; IPMK; INOSITOL POLYPHOSPHATE MULTIKINASE; BREAST-CANCER; EXPRESSION PROFILES; TERTIARY STRUCTURE; COLON-CANCER; PROGRESSION; METASTASIS; SIGNATURE; APOPTOSIS; MIR-18A;
D O I
10.3892/ol.2017.5961
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The role of microRNA-18a (miRNA/miR-18a) as a tumor suppressor or promoter in a number of different types of cancer has been reported. However, to date, the expression and the effects of miR-18a in epithelial ovarian cancer (EOC) remain elusive. In the present study, the expression of miR-18a in patient EOC tissues and ovarian cancer cell lines was investigated using the reverse transcription-quantitative polymerase chain reaction. Luciferase assays and western blotting were performed to detect the potential direct targets of miR-18a. An A2780cp intraperitoneal mouse model, and Cell Counting Kit 8, flow cytometry and terminal deoxynucleotidyltrans-ferase-mediated dUTP nick end labeling assays, were used to investigate the effect of miR-18a on tumor growth in vivo and in vitro. The results indicated that the expression of miR-18a was reduced in EOC tissue and in the investigated ovarian cancer cell lines compared with non-malignant (normal) ovarian tissues and the human ovarian epithelium cell line, respectively. Overexpression of miR-18a in the A2780s and A2780cp cell lines significantly induced cell cycle arrest and apoptosis. It was demonstrated that miR-18a directly targets tumor protein p53-regulating inhibitor of apoptosis gene 1 and inositol phosphate multikinase, hence regulating the expression of downstream targets. The A2780cp intraperitoneal mouse model was employed and the results indicated that miR-18a may inhibit A2780cp intraperitoneal tumor growth in vivo by inhibiting proliferation and inducing apoptosis. Together, the results of the present study demonstrated that miR-18a has a role as a tumor suppressor by inhibiting proliferation and inducing apoptosis. Assessment of miR-18a expression may provide a novel method for diagnosis and be a therapeutic target for EOC.
引用
收藏
页码:4039 / 4046
页数:8
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