Acquisition of radioresistance in docetaxel-resistant human lung adenocarcinoma cells is linked with dysregulation of miR-451/c-Myc-survivin/rad-51 signaling

摘要: Chemoresistant tumors usually fail to respond radiotherapy. However, the mechanisms involved in chemo- and radiotherapy cross resistance are not fully understood. Previously, we have identified microRNA (miR)-451 as a tumor suppressor lung adenocarcinoma (LAD). whether miR-451 plays critical roles LAD is unclear. Here, established two docetaxel-resistant cell models (SPC-A1/DTX H1299/DTX), showed that was significantly downregulated cells. Gain - loss of function assays indicated re-expression could reverse radioresistance cells both vitro vivo through promoting apoptosis DNA double-strand breaks (DSBs). The proto-oncogene c-Myc direct target miR-451, inhibited survivin rad-51 expression by reducing amount protein binding their promoters. Silencing phenocopy effects upregulation, restoration partially rescue effect upregulation on radiosensitivity Therefore, dysregulation miR-451/c-Myc-survivin/rad-51 signaling responsible for cells, targeting it will be potential strategy reversing patients.