MicroRNA-487a-3p functions as a new tumor suppressor in prostate cancer by targeting CCND1

被引:35
|
作者
Wang, Mingming [1 ,2 ,3 ]
Yu, Wanpeng [1 ]
Gao, Jun [1 ]
Ma, Wenqiang [1 ]
Frentsch, Macro [4 ]
Thiel, Andreas [4 ]
Liu, Mei [5 ]
Rahman, Nafis [6 ]
Qin, Zhihai [7 ]
Li, Xiangdong [1 ,2 ,3 ,8 ]
机构
[1] China Agr Univ, Beijing Adv Innovat Ctr Food Nutr & Human Hlth, Beijing 100193, Peoples R China
[2] China Agr Univ, State Key Lab Agrobiotechnol, Coll Biol Sci, Beijing, Peoples R China
[3] Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou, Guangdong, Peoples R China
[4] Charite Univ Med Berlin, Berlin Brandenburger Ctr Regenerat Therapies BCRT, Regenerat Immunol & Aging, Berlin, Germany
[5] Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing, Peoples R China
[6] Univ Turku, Dept Physiol, Inst Biomed, Turku, Finland
[7] Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China
[8] Med Univ Bialystok, Dept Reprod & Gynecol Endocrinol, Bialystok, Poland
关键词
CCND1; miR-487a-3p; prostate cancer; tumor suppressor; CYCLIN D1; METASTASIS; PROLIFERATION; EXPRESSION; MICRORNAS; CELLS; RISK;
D O I
10.1002/jcp.29078
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Prostate cancer (PCa) is one of the major health problems of the aging male. The roles of dysregulated microRNAs in PCa remain unclear. In this study, we mined the public published data and found that miR-487a-3p was significantly downregulated in 38 pairs of clinical prostate tumor tissues compared with the normal tissues. We further verified this result by in situ hybridization on tissue chip and quantitative real-time polymerase chain reaction (qRT-PCR) in PCa/normal cells. miR-487a-3p targeting of cyclin D1 (CCND1) was identified using bioinformatics, qRT-PCR and western blot analyses. The cellular proliferation, cell cycle, migration, and invasion were assessed by cell counting kit-8, flow cytometry analysis and transwell assay. We discovered that overexpression of miR-487a-3p suppressed PCa cell growth, migration, invasion by directly targeting CCND1. Knockdown of CCND1 in PCa cells showed similar results. Meanwhile, the expression level of CCND1 was significantly upregulated in the PCa tissues and cell lines, which presented negative correlation with the expression of miR-487a-3p. More important, we demonstrated significantly reduced growth of xenograft tumors of stable miR-487a-3p-overexpressed human PCa cells in nude mice. Taken together, for the first time, our results revealed that miR-487a-3p as a tumor suppressor of PCa could target CCND1. Our finding might reveal miR-487a-3p could be potentially contributed to the pathogenesis and a clinical biomarker or the new potential therapeutic target of PCa.
引用
收藏
页码:1588 / 1600
页数:13
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