miR-153 enhances the therapeutic effect of radiotherapy by targeting JAG1 in pancreatic cancer cells
ONCOLOGY LETTERS(2021)
Abstract
Pancreatic cancer is one of the deadliest diseases, due to the lack of early symptoms and resistance to current therapies, including radiotherapy. However, the mechanisms of radioresistance in pancreatic cancer remain unknown. The present study explored the role of microRNA-153 (miR-153) in radioresistance of pancreatic cancer. It was observed that miR-153 was downregulated in pancreatic cancer and positively correlated with patient survival time. Using stably-infected pancreatic cancer cells that overexpressed miR-153 or miR-153 inhibitor, it was found that miR-153 overexpression sensitized pancreatic cancer cells to radiotherapy by inducing increased cell death and decreased colony formation, while cells transfected with the miR-153 inhibitor promoted radioresistance. Further investigation demonstrated that miR-153 promoted radiosensitivity by directly targeting jagged canonical Notch ligand 1 (JAG1). The addition of recombinant JAG1 protein in the cell cultures reversed the therapeutic effect of miR-153. The present study revealed a novel mechanism of radioresistance in pancreatic cancer and indicated that miR-153 may serve as a potential therapeutic target for radioresistance.
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Key words
microRNA-153,jagged canonical Notch ligand 1,pancreatic cancer,radioresistance,cell apoptosis
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