Research Papers:

MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b

Giuseppina Roscigno, Cristina Quintavalle, Elvira Donnarumma, Ilaria Puoti, Angel Diaz-Lagares, Margherita Iaboni, Danilo Fiore, Valentina Russo, Matilde Todaro, Giulia Romano, Renato Thomas, Giuseppina Cortino, Miriam Gaggianesi, Manel Esteller, Carlo M. Croce _ and Gerolama Condorelli

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Oncotarget. 2016; 7:580-592. https://doi.org/10.18632/oncotarget.5979

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Giuseppina Roscigno1,2, Cristina Quintavalle1,2, Elvira Donnarumma3, Ilaria Puoti1, Angel Diaz-Lagares4, Margherita Iaboni1, Danilo Fiore1, Valentina Russo1, Matilde Todaro5, Giulia Romano6, Renato Thomas7, Giuseppina Cortino7, Miriam Gaggianesi5, Manel Esteller4, Carlo M. Croce6, Gerolama Condorelli1,2

1Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, Italy

2IEOS-CNR, Naples, Italy

3IRCCS-SDN, Naples, Italy

4Epigenetic and Cancer Biology Program (PEBC) IDIBELL, Hospital Duran I Reynals, Barcelona, Spain

5Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy

6Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

7Department of Surgical and Oncology, Clinica Mediterranea, Naples, Italy

Correspondence to:

Gerolama Condorelli, e-mail: [email protected]

Keywords: microRNAs, breast cancer, cancer stem cells, DNMT

Received: June 15, 2015     Accepted: October 09, 2015     Published: October 19, 2015


Cancer stem cells (CSCs) are a small part of the heterogeneous tumor cell population possessing self-renewal and multilineage differentiation potential as well as a great ability to sustain tumorigenesis. The molecular pathways underlying CSC phenotype are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that play a powerful role in biological processes. Early studies have linked miRs to the control of self-renewal and differentiation in normal and cancer stem cells. We aimed to study the functional role of miRs in human breast cancer stem cells (BCSCs), also named mammospheres. We found that miR-221 was upregulated in BCSCs compared to their differentiated counterpart. Similarly, mammospheres from T47D cells had an increased level of miR-221 compared to differentiated cells. Transfection of miR-221 in T47D cells increased the number of mammospheres and the expression of stem cell markers. Among miR-221’s targets, we identified DNMT3b. Furthermore, in BCSCs we found that DNMT3b repressed the expression of various stemness genes, such as Nanog and Oct 3/4, acting on the methylation of their promoters, partially reverting the effect of miR-221 on stemness. We hypothesize that miR-221 contributes to breast cancer tumorigenicity by regulating stemness, at least in part through the control of DNMT3b expression.

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