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

Binghai Chen; Lujing Duan; Guangming Yin; Jing Tan; Xianzhen Jiang

doi:10.1179/1973947813Y.0000000092

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

J Chemother. 2013 Aug;25(4):229-38. doi: 10.1179/1973947813Y.0000000092. Epub 2013 May 7.

Authors

Binghai Chen¹, Lujing Duan, Guangming Yin, Jing Tan, Xianzhen Jiang

Affiliation

¹ Department of Urology, Third Xiang-Ya Hospital of Central South University, Changsha 410000, China.

PMID: 23816136
DOI: 10.1179/1973947813Y.0000000092

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Apoptosis / drug effects
CDC2 Protein Kinase
Carcinoma, Renal Cell / drug therapy*
Carcinoma, Renal Cell / genetics
Cell Cycle Proteins / antagonists & inhibitors*
Cell Cycle Proteins / genetics
Cell Line, Tumor
Cyclin B / drug effects
Cyclin-Dependent Kinases
Drug Synergism
Fluorouracil / pharmacology*
Fluorouracil / therapeutic use
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms / drug therapy*
Kidney Neoplasms / genetics
MicroRNAs / pharmacology*
MicroRNAs / therapeutic use
Molecular Targeted Therapy / methods*
Nuclear Proteins / antagonists & inhibitors*
Nuclear Proteins / genetics
Protein-Tyrosine Kinases / antagonists & inhibitors*
Protein-Tyrosine Kinases / genetics
Up-Regulation

Substances

Cell Cycle Proteins
Cyclin B
MicroRNAs
Nuclear Proteins
Protein-Tyrosine Kinases
WEE1 protein, human
CDC2 Protein Kinase
CDK1 protein, human
Cyclin-Dependent Kinases
Fluorouracil