miR-381, a novel intrinsic WEE1 inhibitor, sensitizes renal cancer cells to 5-FU by up-regulation of Cdc2 activities in 786-O

Abstract

Background: Few researches on increase of chemotherapy sensitivity by microRNA (miRNA) were reported. We aim to investigate exact role of miR-381 in chemotherapy sensitivity of 5-fluorouracil (5-FU) in renal cancer cells.

Methods: We investigated the cell survival, cell-cycle and apoptosis of 786-O and HK-2 cells treated with miR-381 and 5-FU. IC₅₀ of 5-FU was calculated. To study apoptosis and G₂/M arrest, we determined pHH3, mitotic index and caspase-3/7 activity.

Results: We showed that miR-381 combined with 5-FU inhibited proliferation and potentiated the anti-tumour efficacies of 5-FU at tolerated concentration in vitro. miR-381 combined with 5-FU led to Cdc2 activation, mitotic catastrophe, and cell apoptosis through inhibitory WEE1. WEE1 was also validated as the direct target of miR-381. IC₅₀ of 5-FU decreased significantly in the presence of miR-381.

Conclusion: miR-381 increases sensitivity of 786-O cells to 5-FU by inhibitory WEE1 and increase of Cdc2 activity.

Keywords:

• 5-FU
• Cdc2
• Chemotherapy
• MicroRNA
• miR-381
• Renal cell cancer
• WEE1

This work was supported by a grant from the 125 Talents Program (Guangming Yin) of Third Xiang-Ya Hospital in China.