MicroRNA-138 Regulates DNA Damage Response in Small Cell Lung Cancer Cells by Directly Targeting XXXX .

@entity5 @entity151 @entity2 @entity6714
@entity2 is the leading cause of @entity5 worldwide and @entity151 ( @entity151 ) accounts for a significant proportion of all @entity2 cases. Even so, the underlying mechanism governing @entity151 development remains poorly understood and @entity151 related @entity5 stands high despite decades of intensive investigation. We noted that both miR-138 and @entity6714 have been implicated in development of @entity5 . Also, there is a recent report showing the role of miR-138 in mediating DNA damage response by targeting @entity6714 . In light of these data, we sought to characterize the role of miR-138 for @entity151 cell growth and cell-cycle progression by regulating @entity6714 expression. Results showed that miR-138 is significantly down-regulated in @entity151 tissues as well as in three @entity151 cell lines. After successfully engineering miR-138 overexpression in one of the @entity151 cell lines, NCI-H2081, we observed a remarkable reduction of cell growth and a significant inhibition on cell-cycle progression. Moreover, we were able to show that miR-138 potently inhibits @entity6714 expression, which suggests that @entity6714 may serve as a downstream executor for miR-138. Consistent with this hypothesis, we found that engineered @entity6714 knockdown achieves a similar effect as observed for miR-138 overexpression in terms of @entity151 growth and cell cycle regulation. We also showed that @entity6714 overexpression largely abolished miR-138-mediated @entity5 cell growth and cell-cycle progression inhibition, which strongly suggests, at least in vitro, that miR-138 potently regulates @entity151 development by targeting @entity6714 . In addition, we found lower miR-138 expression confers @entity151 cells with greater DNA damage repair capacity. Finally, we were able to show miR-138 overexpression inhibits DNA damage repair in @entity151 cells while miR-138 knockdown further facilitates DNA damage repair in these cells after IR. To date, there has been no study showing the role of miR-138/ @entity6714 machinery in @entity151 development. Our results may shed a light to development of new lines of @entity151 diagnosis and treatment approaches.
