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

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, mills 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 mills 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 antitumor approach for, integrated cancer therapy. MiR-221 and mill-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 p27(KiP1) (CDKN1S), a gatekeepers of the G(1)/S cell cycle check-point CDK inhibitor protein. MiR-221/222 target the p27(KiP1) mRNA, causing a down-regulation of the protein; lower levels of p27(Kip1) protein lead to a state of uncontrolled proliferation, typical of aggressive tumors. In this review, we describe the role of mill-221/222 in cancer progression, focusing on the potential use as therapeutic targets for cancer.