Medical Hypothesis No small matter: microRNAs -- key regulators of cancer stem cells
Qing Ji, David Karnak, Ping Hao, Rongquan Wang, Liang Xu
Department of Digestive Diseases, The First Affiliated Hospital, Department of Oncology, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400038, China; Department of Radiation Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
Received February 5, 2010, accepted March 5, 2010, available online March 12, 2010
Abstract: Emerging evidence demonstrates that both tumor suppressor and oncogenic miRNAs play an essential role in stem cell self-renewal and differentiation by negatively regulating the expression of certain key genes in stem cells. It seems logical that they may also be critical players in cancer stem cells. Though small in size, miRNAs play a key role in the epigenetic regulation of cancer stem cells. Specifically, the imbalance of oncogenic vs. tumor suppressor miRNAs may lead to dysregulation of cancer stem cells, thus causing excessive self-renewal and survival of cancer stem cells, and resistance to chemo/radiotherapy. We postulate that restoring the balance of miRNAs will correct this dysregulation via the direct and simultaneous modulation of downstream stem cell pathways involved in cancer stem cell self-renewal and/or differentiation. The resultant restoration of key regulatory pathways could improve therapeutic response. Restoring tumor suppressor miRNAs and/or inhibiting oncogenic miRNAs may provide a novel molecular therapy for human cancers, potentially via modulating cancer stem cells. (IJCEM1002003).
Address all correspondence to: Qing Ji, M.D., Ph.D. Department of Digestive Diseases The First Affiliated Hospital Third Military Medical University Chongqing 400038 China Tel: 86-13500380255 E-mail: qingji@hotmail.com
Liang Xu, M.D., Ph.D. Department of Radiation Oncology Division of Cancer Biology University of Michigan 4424E Med Sci I 1301 Catherine St. Ann Arbor, MI 48109-5637 Tel: 734-615-7017 Fax: 734-615-3422 E-mail: liangxu@umich.edu