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

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., Fassan, M., Coppola, V., Garofalo, M., & Croce, C. Abstract A085: miR-222/221 in aggressive breast cancer. Presented at AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications, San Diego, CA, USA; October 3-6, 2013

• Presentation Conference Type: Conference Paper (published)
• Conference Name: AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications
• 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
• Public URL: https://keele-repository.worktribe.com/output/445653