Please use this identifier to cite or link to this item:
Scopus Web of ScienceĀ® Altmetric
Type: Journal article
Title: MicroRNA networks regulated by all-trans retinoic acid and Lapatinib control the growth, survival and motility of breast cancer cells
Author: Fisher, J.
Terao, M.
Fratelli, M.
Kurosaki, M.
Paroni, G.
Zanetti, A.
Gianni, M.
Bolis, M.
Lupi, M.
Tsykin, A.
Goodall, G.
Garattini, E.
Citation: Oncotarget, 2015; 6(15):13176-13200
Publisher: Impact Journals
Issue Date: 2015
ISSN: 1949-2553
Statement of
James Neil Fisher, Mineko Terao, Maddalena Fratelli, Mami Kurosaki, Gabriela Paroni, Adriana Zanetti, Maurizio Gianni, Marco Bolis, Monica Lupi, Anna Tsykin, Gregory J. Goodall, Enrico Garattini
Abstract: SKBR3-cells, characterized by ERBB2/RARA co-amplification, represent a subgroup of HER2+ breast-cancers sensitive to all-trans retinoic acid (ATRA) and Lapatinib. In this model, the two agents alone or in combination modulate the expression of 174 microRNAs (miRs). These miRs and predicted target-transcripts are organized in four interconnected modules (Module-1 to -4). Module-1 and Module-3 consist of ATRA/Lapatinib up-regulated and potentially anti-oncogenic miRs, while Module-2 contains ATRA/Lapatinib down-regulated and potentially pro-oncogenic miRs. Consistent with this, the expression levels of Module-1/-3 and Module-2 miRs are higher and lower, respectively, in normal mammary tissues relative to ductal-carcinoma-in-situ, invasive-ductal-carcinoma and metastases. This indicates associations between tumor-progression and the expression profiles of Module-1 to -3 miRs. Similar associations are observed with tumor proliferation-scores, staging, size and overall-survival using TCGA (The Cancer Genome Atlas) data. Forced expression of Module-1 miRs, (miR-29a-3p; miR-874-3p) inhibit SKBR3-cell growth and Module-3 miRs (miR-575; miR-1225-5p) reduce growth and motility. Module-2 miRs (miR-125a; miR-193; miR-210) increase SKBR3 cell growth, survival and motility. Some of these effects are of general significance, being replicated in other breast cancer cell lines representing the heterogeneity of this disease. Finally, our study demonstrates that HIPK2-kinase and the PLCXD1-phospholipase-C are novel targets of miR-193a-5p/miR-210-3p and miR-575/miR-1225-5p, respectively.
Keywords: breast cancer; lapatinib; microRNA; network analysis; retinoic acid
Rights: All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. PII: 3759
RMID: 0030031890
DOI: 10.18632/oncotarget.3759
Appears in Collections:Medicine publications

Files in This Item:
File Description SizeFormat 
hdl_93447.pdfPublished version5.98 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.