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REVIEWS  MicroRNAs: from basic research to therapeutic applications 

Minerva Biotecnologica 2014 June;26(2):67-74


language: English

Targeting the miR-221/miR-222 cluster in cancer therapy

Brognara E., Fabbri E., Breveglieri G., Finotti A., Bianchi N., Zuccato C., Gambari R.

Section of Biochemistry and Molecutal Biology, Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy


MicroRNAs (miRNAs, miRs) are a family of small non-coding RNAs of 19-24 nucleotides, highly conserved during evolution, that are able to regulate gene expression by a sequence-selective targeting of mRNAs: depending on the degree of complementarity with target mRNA sequence, miRs can lead to a translational repression or mRNA degradation. MiRNAs play an essential role in malignancy. There is a large body of evidence that dysregulation of miRNAs is an hallmark of cancer; its occurs because many miRs are located in “fragile sites”, which are frequently deleted in cancer. MicroRNAs that are frequently over-expressed in neoplastic tissues compared to normal tissues and regulate tumor suppressor proteins are defined “oncomiRs”. Silencing oncomiRs could represent a novel anti-tumor approach for integrated cancer therapy. MiR-221 and miR-222 are two highly homologous miRs, whose up-regulation has been recently described in several types of human tumors. One of the main targets of miR-221/222 is the onco-suppressor p27Kip1 (CDKN1B), a gatekeepers of the G1/S cell cycle check-point CDK inhibitor protein. MiR-221/222 target the p27Kip1 mRNA, causing a down-regulation of the protein; lower levels of p27Kip1 protein lead to a state of uncontrolled proliferation, typical of aggressive tumors. In this review, we describe the role of miR-221/222 in cancer progression, focusing on the potential use as therapeutic targets for cancer.

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