Possible carcinogenesis of tumor suppressor let-7

Cancer stem cells (CSCs), a group showing high capacities of sphere-forming and self renewal, are blamed for tumor initiation, recurrence and therapy resistance. Therefore, therapeutics specifically targeting and perishing CSCs may be promising. Let-7 miRNAs, one of the earliest discovered miRNAs, were considered as novel and vital agents to eliminate cancer and CSCs. However, in recent researches, many regulatory loops among let-7 and its targeted genes were noticed; the regulation of let-7 caused by its hunting mRNAs helped to form the hypotheses that hunters and preys may swap their roles when in confrontations. Besides, the evil side of let-7 was discovered occasionally, therefore, we hypothesize that dual characteristics of let-7 do exist, which will have significant impacts on anticancer research. Targeted therapies against cancer and CSCs by using let-7 or other miRNAs as weapons should be thought twice before clinical application. (C) 2013 Elsevier Ltd. All rights reserved.