MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer

被引:121
作者
Liu, Guoyan [1 ,5 ]
Sun, Yan [1 ,6 ]
Ji, Ping [1 ]
Li, Xia [1 ,8 ]
Cogdell, David [1 ]
Yang, Da [1 ]
Kerrigan, Brittany C. Parker [1 ]
Shmulevich, Ilya [9 ]
Chen, Kexin [6 ,7 ]
Sood, Anil K. [2 ,3 ,4 ]
Xue, Fengxia [5 ]
Zhang, Wei [1 ,4 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Ctr RNAi & Noncoding RNA, Houston, TX 77030 USA
[5] Tianjin Med Univ Gen Hosp, Dept Gynecol & Obstet, Tianjin, Peoples R China
[6] Tianjin Med Univ Canc Inst & Hosp, Dept Pathol, Tianjin, Peoples R China
[7] Tianjin Med Univ Canc Inst & Hosp, Dept Epidemiol & Biostat, Tianjin, Peoples R China
[8] Fourth Mil Med Univ, State Key Lab Canc Biol, Dept Biochem & Mol Biol, Xian 710032, Peoples R China
[9] Inst Syst Biol, Seattle, WA USA
基金
美国国家卫生研究院;
关键词
miR-506; ovarian carcinoma; proliferation; senescence; FOXM1; MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR; FOXM1; CDK4; PROGRESSION; MICRORNAS; PD0332991; SURVIVAL; TRIAL;
D O I
10.1002/path.4348
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
引用
收藏
页码:308 / 318
页数:11
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