Effect of miR-449a on radiosensitivity of pancreatic cancer cells / 中华放射肿瘤学杂志

ABSTRACT

Objective The purpose of this study is to investigate the effect of miR-449a on pancreatic cancer cells and the molecular mechanism. Methods The expression levels of miR-449a in pancreatic cancer cells treated or untreated with radiation was detected by qRT-PCR.High expression of miR-449a was achieved by transfecting miR-449a mimics into SW1990 cells. The cell growth,apoptosis and colony formation ability was assessed by MTT assay,flow cytometry and colony formation assay,respectively. The relationship of miR-449a and Cyclin D1 was determined by the TargetScan and dual luciferase reporter. Immunohistochemistry was used to examine protein levels of Cyclin D1 in pancreatic cancer and normal pancreas tissues. Si-Cyclin D1 was used to detecte the effect of Cyclin D1 on radiosensitivity of pancreatic cancer cells. Results The expression levels of miR-449a in pancreatic cancer cells with radiation treatment were decreased significantly. Mir-449a mimics increased the cell proliferation rates and apoptosis rates obviously,and decreased the colony formation ability in SW1990 cells treated with radiation. Results from the TargetScan and dual luciferase reporter showed that Cyclin D1 was the target of miR-449a. The positive staining rates of Cyclin D1 in pancreatic cancer tissue(85.7%,30/35)was higher than those in normal pancreas tissue(20%,2/10).Knockdown of Cyclin D1 enhanced the radiosensitivity of pancreatic cancer cells.Conclusion MiR-449a enhances the radiosensitivity of pancreatic cancer cells by targeting Cyclin D1.