A microRNA-dependent program controls @entity876 -independent survival and chemosensitivity in @entity1 and XXXX @entity957 .

@entity1 @entity9486 @entity5 @entity19 @entity4206 @entity957 @entity73361 @entity876
The @entity876 @entity5 suppressor, a central mediator of chemosensitivity in normal cells, is functionally inactivated in many @entity1 @entity5 . Therefore, a central challenge in @entity1 @entity5 therapy is the identification of pathways that control @entity5 cell survival and chemosensitivity in the absence of functional @entity876 . The @entity876 -related transcription factors @entity4206 and @entity9486 exhibit distinct functions   @entity9486 mediates chemosensitivity while @entity4206 promotes proliferation and cell survival   and are both overexpressed in @entity957 ( @entity957 ). However, how @entity4206 and @entity9486 interact functionally and govern the balance between prosurvival and proapoptotic programs in SCC remains elusive. Here, we identify a microRNA-dependent mechanism of @entity4206 / @entity9486 crosstalk that regulates @entity876 -independent survival of both @entity1 and @entity19 SCC. We first discovered that a subset of @entity4206 -regulated microRNAs target @entity9486 for inhibition. One of these, @entity73361 -5p, expression of which was repressed by @entity4206 , was activated by proapoptotic @entity9486 isoforms in both normal cells and @entity5 cells in vivo. Chemotherapy caused @entity4206 / @entity9486 -dependent induction of this microRNA, thereby limiting chemosensitivity due to microRNA-mediated feedback inhibition of @entity9486 . Importantly, inhibiting @entity73361 interrupted this feedback and thereby suppressed @entity5 cell viability and induced dramatic chemosensitivity both in vitro and in vivo. Thus, we have identified a direct, microRNA-dependent regulatory circuit mediating inducible chemoresistance, whose inhibition may provide a new therapeutic opportunity in @entity876 -deficient @entity5 .
