Apoptosis induction by the stem cell factor LIN28A

Background information: Lin28A and its paralog Lin28B are RNA binding proteins expressed in stem and progenitor cells, regulating the balance between their proliferation and differentiation. In-vivo and in-vitro experiments have shown that overexpression of these genes leads to abnormal cell proliferation, which results in many cases in cell transformation and tumor formation. Results: Here we show, for the first time, that Lin28A overexpression can also lead to the opposite effect, i.e. apoptosis induction. We further demonstrate that this effect is specific to Lin28A but not to Lin28B and that it is mediated via the Let-7 independent pathway in a complex mechanism that involves at least several proteins. Conclusions and Significance: This unexpected observation suggests that cell fate regulation by Lin28 is dependent on a specific cellular/genetic context. Unraveling the cellular and molecular mechanisms underlying this Lin28A overexpression effect may pave the way for novel tumor therapeutic strategies, as Lin28 is commonly expressed in many types of tumors but not in most normal adult cells.