From microRNA functions to microRNA therapeutics: Novel targets and novel drugs in breast cancer research and treatment (Review)

Piva,Roberta; Spandidos,Demetrios A.; Gambari,Roberto

doi:10.3892/ijo.2013.2059

From microRNA functions to microRNA therapeutics: Novel targets and novel drugs in breast cancer research and treatment (Review)

Authors:
- Roberta Piva
- Demetrios A. Spandidos
- Roberto Gambari
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Affiliations: Department of Biomedical and Specialty Surgical Sciences, Ferrara University, Ferrara, Italy, Department of Clinical Virology, University of Crete School of Medicine, Heraklion, Crete, Greece, Department of Life Sciences and Biotechnology, Ferrara University, Ferrara, Italy
Published online on: August 12, 2013 https://doi.org/10.3892/ijo.2013.2059
Pages: 985-994
Copyright: © Piva et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

MicroRNAs (miRNAs or miRs) are a family of small non‑coding RNAs that regulate gene expression by the sequence-selective targeting of mRNAs, leading to translational repression or mRNA degradation, depending on the degree of complementarity with target mRNA sequences. miRNAs play a crucial role in cancer. In the case of breast tumors, several studies have demonstrated a correlation between: i) the expression profile of oncogenic miRNAs (oncomiRs) and tumor suppressor miRNAs; and ii) the tumorigenic potential of triple-negative [estrogen receptor (ER), progesterone receptor (PR) and Her2/neu] primary breast cancers. Among the miRNAs involved in breast cancer, miR-221 plays a crucial role for the following reasons: i) miR-221 is significantly overexpressed in triple-negative primary breast cancer; ii) the oncosuppressor p27Kip1, a validated miR-221 target is downregulated in aggressive cancer cell lines; and iii) the upregulation of a key transcription factor, Slug, appears to be crucial, since it binds to the miR-221/miR-222 promoter and is responsible for the high expression of the miR-221/miR-222 cluster in breast cancer cells. A Slug/miR-221 network has been suggested, linking miR-221 activity with the downregulation of a Slug repressor, leading to Slug/miR-221 upregulation and p27Kip1 downregulation. Interference with this process can be achieved using antisense miRNA (antagomiR) molecules targeting miR-221, inducing the downregulation of Slug and the upregulation of p27Kip1.

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