The Akt-associated microRNAs
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Cellular and Molecular Life Sciences
MULTI-AUTHOR REVIEW
The Akt-associated microRNAs Min Xu • Yin-Yuan Mo
Received: 8 August 2012 / Revised: 9 August 2012 / Accepted: 9 August 2012 / Published online: 31 August 2012 Ó Springer Basel AG 2012
Abstract As master gene regulators, microRNAs are involved in diverse cellular pathways. It is well known that microRNAs are often dysregulated in many types of cancer and other human diseases. In cancer, microRNAs may function as oncogenes or tumor suppressors. Interestingly, recent evidence suggests that microRNA-mediated gene regulation interconnects with the Akt pathway, forming an Akt–microRNA regulatory network. MicroRNAs and Akt in this network work together to exert their cellular functions. Thus, a better understanding of this Akt–microRNA regulatory network is critical to successful targeting of the PI3K/Akt pathway for cancer therapy. We review recent advances in the understanding of how microRNAs affect Akt activity as well as how microRNAs are regulated through the Akt pathway. We also briefly discuss the clinical implication of gene regulation mediated through Akt-associated microRNAs. Keywords Akt microRNAs Akt–microRNA regulatory network miR-145 miR-101
M. Xu Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu, People’s Republic of China M. Xu Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA
Introduction Serine/threonine kinase (Akt)/protein kinase B (PKB) is a key downstream target of the signaling pathway mediated by phosphoinositide-3 kinase (PI3K) and plays an important role in regulation of diverse cellular processes. Inappropriate activation of Akt has been reported in many types of human disease, in particular cancer. As a major pathway involved in cell growth and proliferation, the Akt pathway has been intensively investigated. Recent evidence suggests that newly discovered microRNAs are important molecular players in this pathway, thus adding another layer of complexity. For the sake of simplicity, we focus on two groups of microRNAs, i.e., those upstream and those downstream of Akt. The upstream microRNAs are those capable of regulating Akt activity, whereas the downstream microRNAs often serve as Akt effectors. Apparently, these microRNAs and Akt work together to exert their cellular functions. Therefore, any new information on these microRNAs will add to our understanding of this Akt–microRNA regulatory network and help in the development of better strategies for cancer treatment. We first discuss how microRNAs regulate gene expression, and their function in general. In the major part of this article, we then discuss these two groups of microRNAs, and their roles in gene expression and tumorigenesis. We take miR145 and miR-101 as examples for these two groups of microRNAs.
MicroRNAs as master gene regulators Y.-Y. Mo (&) Cancer Institute, University of Mississippi Medical Center, 2500 N State
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