let-7 and miR-17-92: Small-sized major players in lung cancer development

MicroRNA (miRNA)-encoding small non-coding RNA have been recognized as important regulators of a number of biological processes that inhibit the expression of hundreds of genes. Accumulating evidence also indicates the involvement of miRNA alterations in various types of human cancer, including lung cancer, which has long been the leading cause of cancer death in economically well-developed countries, including Japan. We previously found that downregulation of members of the tumor-suppressive let-7 miRNA family and overexpression of the oncogenic miR-17-92 miRNA cluster frequently occur in lung cancers, and molecular insight into how these miRNA alterations may contribute to tumor development has been rapidly accumulating. The present review summarizes recent advances in elucidation of the molecular functions of these miRNA in relation to their roles in the pathogenesis of lung cancer. Given the crucial roles of miRNA alterations, additional studies are expected to provide a better understanding of the underlying molecular mechanisms of disease development, as well as a foundation for novel strategies for cancer diagnosis and treatment of this devastating disease. (Cancer Sci 2011; 102: 9-17).