miR-449a: a potential therapeutic agent for cancer

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Abstract

MicroRNAs (miRNAs) have been reported to be associated with cancer progression and carcinogenesis. They are small, highly conserved, noncoding RNA molecules consisting of 19–25 nucleotides. By binding to complementary binding sites within the 3′-untranslated region of target mRNAs, miRNAs inhibit the translation of mRNAs or promote their degradation. miRNAs play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. Similarly, several studies have shown that miRNAs are involved in regulating various biological processes, including apoptosis, proliferation, cellular differentiation, signal transduction, and carcinogenesis. Among miRNAs, one that may be of particular interest in cancer biology is miR-449a, which has been reported to inhibit tumor growth, invasion, and metastasis, and to promote apoptosis and differentiation through the transforming growth factor-β activated kinase 1, NOTCH, nuclear factor-κB/P65/vascular endothelial growth factor, retinoblastoma-E2F, mitogen-activated protein kinase signaling pathways, WNT–β-catenin signaling, tumor protein P53, and androgen receptor signaling pathways. The miR-449 cluster is located in the second intron of CDC20B on chromosome 5q11.2, a region that has been identified as a susceptibility locus in cancer, and the abnormal expression of miR-449a may be related to the occurrence and development of tumors. As one example, miR-449a has been reported to be involved in the development of carcinoma and may be a potential prognostic indicator. On the basis of the putative pathogenetic relationships between cancer and miR-449a, we consider that miR-449a has the potential to serve as a therapeutic agent for the treatment of some types of cancer. In this review, the role of miR-449a in tumorigenesis and its mechanism of action are explored. Furthermore, its potential as a therapeutic agent in cancer treatment is considered.

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