Gianpiero Di Leva g.dileva@keele.ac.uk
Abstract A085: miR-222/221 in aggressive breast cancer
Di Leva, Gianpiero; Piovan, Claudia; Cheung, Douglas; Briskin, Daniel; Kumar, Arpan; Nuovo, Gerard; Fassan, Matteo; Coppola, Vincenzo; Garofalo, Michela; Croce, Carlo
Authors
Claudia Piovan
Douglas Cheung
Daniel Briskin
Arpan Kumar
Gerard Nuovo
Matteo Fassan
Vincenzo Coppola
Michela Garofalo
Carlo Croce
Abstract
MicroRNAs (miRNAs) are small non coding RNAs that regulate gene expression at post-transcriptional level through translational inhibition and/or degradation of mRNA target genes. Recent evidence points to a widespread role for miRNAs in the initiation and progression of tumorigenesis in a plethora of tissues including the mammary gland. Aberrant miRNA expression profiles have been described in breast cancer specimens compared to normal tissues, discriminating breast tumors with different clinico-biological phenotypes. In our previous publications, we have demonstrated that miR-222/221 cluster is highly expressed in aggressive breast cancer and high levels of miR-222/221 may confer a proliferation advantage to cancer cells and resistance to therapeutic agents by repressing several genes such as ERα;, CDKN1B, BIM, FOXO3, CAV1, PTEN. To demonstrate the in vivo role of miR-222/221 cluster in breast cancer initiation and progression, we have genetically deleted miR-222/221 gene in the MMTV-PyVT mouse model that develops multifocal mammary adenocarcinoma and lung metastatic lesions in 80% of the population. The tumor latency and multiplicity were assessed and none of these parameters were significantly affected by miR-222/221 ablation. Interestingly, lack of miR-222/221 impairs the development of lung metastasis with a reduction of the metastatic load of the lung. Moreover, metastases arising from miR-222/221 deficient cells present a greater cytoarchitectural similarity and a reduced rate of mitosis and apoptosis. We also show that loss of miR-222/221 modulates the transcriptome and miRNA expression profiles of mouse breast tumors and cancer cells, stimulating a stronger estrogen receptor alpha transcriptional network and a suppression of the cancer stem cells population.
Citation
Di Leva, G., Piovan, C., Cheung, D., Briskin, D., Kumar, A., Nuovo, G., …Croce, C. (2013). Abstract A085: miR-222/221 in aggressive breast cancer. Molecular Cancer Research, 11(10_Supplement), A085-A085. https://doi.org/10.1158/1557-3125.advbc-a085
Journal Article Type | Conference Paper |
---|---|
Conference Name | AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications |
Conference Location | San Diego, CA, USA; October 3-6, 2013 |
Online Publication Date | Jul 31, 2014 |
Publication Date | Oct 1, 2013 |
Deposit Date | Jun 12, 2023 |
Journal | Molecular Cancer Research |
Print ISSN | 1541-7786 |
Electronic ISSN | 1557-3125 |
Publisher | American Association for Cancer Research |
Peer Reviewed | Peer Reviewed |
Volume | 11 |
Issue | 10_Supplement |
Pages | A085-A085 |
DOI | https://doi.org/10.1158/1557-3125.advbc-a085 |
Keywords | Cancer Research; Oncology; Molecular Biology |
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