MicroRNA-567 dysregulation contributes to carcinogenesis of breast cancer, targeting tumor cell proliferation, and migration

被引:35
作者
Bertoli, Gloria [1 ]
Cava, Claudia [1 ]
Diceglie, Cecilia [2 ,3 ]
Martelli, Cristina [3 ]
Rizzo, Giampiero [4 ]
Piccotti, Francesca [4 ,5 ]
Ottobrini, Luisa [1 ,3 ]
Castiglioni, Isabella [1 ]
机构
[1] Natl Res Council IBFM CNR, Inst Mol Bioimaging & Physiol, Via F Cervi 93, I-20090 Milan, Italy
[2] Univ Milano Bicocca, Tecnomed Fdn, Monza, Italy
[3] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy
[4] Fdn Maugeri, IRCCS, Dept Med Oncol, Pavia, Italy
[5] Fdn Salvatore Maugeri, IRCCS, Inst Oncol Biobank Bruno Boerci, Lab Expt Oncol & Pharmacogen, Pavia, Italy
关键词
MicroRNA/miRNA; Breast cancer; Prognosis; Biomarker; Proliferation; KARYOPHERIN ALPHA-2 EXPRESSION; HISTOLOGIC GRADE; IN-VITRO; RECURRENCE; ACTIVATION; PROGNOSIS; SUBTYPES; MARKERS; ASSAY;
D O I
10.1007/s10549-016-4079-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We demonstrated that Hsa-miR-567 expression is significantly downregulated in poor prognosis breast cancer, compared to better prognosis breast cancer, having a role in the control of cell proliferation and migration by regulating KPNA4 gene. In this study, based on our previously published in silico results, we proved both in vitro (cell line studies) and ex vivo (clinical studies), that Hsa-miR-567 expression is significantly downregulated in breast cancer with poor prognosis when compared to breast cancer with better prognosis. More intriguingly, we demonstrated that the ectopic expression of Hsa-miR-567 in poor prognosis breast cancer cell line strongly inhibits in vitro cell proliferation and migration. Furthermore, we showed in vivo that breast cancer cells, stably expressing Hsa-miR-567, xenografted in mouse, reduce tumor growth ability. Consistently, we found that karyopherin 4 (KPNA4), predicted target gene of Hsa-miR-567 as identified by our in silico analysis, is upregulated in highly aggressive MDA-MB-231 breast cancer cell line and patient tissues with poor prognosis with respect to good prognosis. Our results suggest a potential role of Hsa-miR-567 as a novel prognostic biomarker for BC and as regulator of KPNA4.
引用
收藏
页码:605 / 616
页数:12
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