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

• DOI: 10.1007/s10549-016-4079-2
• Publication Date: 2016-12-20T12:50:51Z
• Authors: Gloria Bertoli; Claudia Cava; Cecilia Diceglie; Cristina Martelli; Giampiero Rizzo; Francesca Piccotti; Luisa Ottobrini; Isabella Castiglioni
• Keywords: 0301 basic medicine; Cancer Research; Carcinogenesis; Down-Regulation; Breast Neoplasms; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; in silico analysis; Animals; Humans; Genetic Predisposition to Disease; Cell Proliferation; Brief Report; Gene Expression Profiling; Computational Biology; Reproducibility of Results; Biomarker; Breast cancer; MicroRNA/miRNA; Prognosis; Proliferation; Tumor Burden; 3. Good health; Gene Expression Regulation, Neoplastic; Disease Models, Animal; MicroRNAs; Oncology; Biomarker; Breast cancer; MicroRNA/miRNA; Prognosis; Proliferation;; Heterografts; Female; RNA Interference; Biomarker; Breast cancer; MicroRNA/miRNA; Prognosis; Proliferation; Oncology; Cancer Research

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.