SAGE-Hindawi Access to Research Journal of Aging Research Volume 2011, Article ID 205378, 11 pages doi:10.4061/2011/205378 Review Article MicroRNAs Regulate Key Effector Pathways of Senescence Andrea Feliciano,1 Beatriz S a´nchez-Sendra,1 Hiroshi Kondoh,2 and Matilde E. LLeonart1 1 Oncology and Molecular Pathology Group, Pathology Department, Fundacil Institut de Recerca Hospital Vall d’Hebron, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain 2 Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan Correspondence should be addressed to Matilde E. LLeonart, melleona@ir.vhebron.net Received 7 February 2011; Accepted 9 March 2011 Academic Editor: Amancio Carnero Copyright © 2011 Andrea Feliciano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MicroRNAs (miRNAs) are small (approximately 22 nt) noncoding endogenous RNA molecules that regulate gene expression and protein coding by base pairing with the 3 untranslated region (UTR) of target mRNAs. miRNA expression is associated with cancer pathogenesis because miRNAs are intimately linked to cancer development. Senescence blocks cell proliferation, representing an important barrier that cells must bypass to reach malignancy. Importantly, certain miRNAs have been shown to have an important role during cellular senescence, which is also involved in human tumorigenesis. Therefore, therapeutic induction of senescence by drugs or miRNA-based therapies is a potential method to treat cancer by inducing a persistent growth arrest in tumors. 1. Introduction miRNAs are small noncoding RNAs (approximately 22 nt) that regulate gene expression by interfering with protein translational machinery and/or inducing degradation of target mRNAs [1]. Hundreds of microRNA (miRNA) genes have been found in animals, plants, and viruses [2–4] making them one of the largest gene families. Recent studies revealed the key roles of miRNAs in diverse regulatory pathways including development timing control, hematopoietic cell diﬀerentiation, apoptosis, cell proliferation, and organ development [2]. miRNAs and their targets constitute remarkably complex regulatory networks because a single miRNA can bind to and regulate many diﬀerent mRNA targets, and conversely, several diﬀerent miRNAs can bind to and cooperatively control a single mRNA target [5]. In general, miRNAs repress protein expression at the posttranscriptional level through base pairing with the 3 -UTR leading to reduced translation, or in some cases, degradation. However, some miRNAs have been shown to bind to the open reading frame or to the 5 -UTR of the target mRNAs. In some cases, miRNAs have been shown to activate rather than inhibit gene expression [6–8]. miRNAs are involved in many aspects of cell biology including physiological modulation and pathological dis- ruption of basic pathways. In this regard, miRNAs are key mediators in cancer where they regulate many aspects of tumorigenesis and tumor progression from the initiating steps to metastasis formation and chemosensitivity [9, 10]. Therefore, miRNA expression may be deregulated in cancer because abnormal miRNA activity may lead to tumorigene- sis. It has been shown that human tumors exhibit distinctive miRNA expression signatures [11]. miRNA expression is tissue speciﬁc, and certain cancer histotypes can be classiﬁed based on miRNA expression proﬁles [12]. Some miRNAs have been found to be upregulated or downregulated in cancer. An overexpressed miRNA that downregulates a tumor suppressor gene is deﬁned as an oncomir, and a downregulated miRNA that normally downregulates the expression of an oncogene is deﬁned as a tumor suppressor miR (TS-miR). However, some miRNAs may function as oncogenes in some cell types and as tumor suppressors in other cell types [13]. Aberrant miRNA expression in cancer due to chromosomal abnormalities, polymorphism, and/or epigenetic changes has a direct impact on miRNA biogenesis. In this study, we reviewed the potential impact of miRNAs in senescence and cancer. We suggest that the biological