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Up-Regulation of miR-204 Enhances Anoikis Sensitivity in Epithelial Ovarian Cancer Cell Line Via Brain-Derived Neurotrophic Factor Pathway In Vitro

2015; BMJ; Volume: 25; Issue: 6 Linguagem: Inglês

10.1097/igc.0000000000000456

1525-1438

Yan Hongliang, Weiguang Wu, GE Hong-yu, Pengfei Li, Zheng Wang,

Cancer Mechanisms and Therapy

Genomic loci encoding miR-204, which was predicted to target brain-derived neurotrophic factor (BDNF), were frequently lost in multiple cancer, including epithelial ovarian cancer (EOC). In this study, we aimed to find out the influence of miR-204 expression level on EOC cell anoikis sensitivity and to explore possible mechanisms of this process.First, we screened EOC cells, which maintain anoikis resistance forming an anoikis pattern. miR-204 expression level and apoptosis were measured, respectively, by quantitative reverse transcriptase polymerase chain reaction and Annexin-V-R-PE/7-amino-actinomycin assay. Then we restored the expression level of miR-204 by transfection with pre-miR-204. miR-204 expression level and apoptosis were measured as before; cell invasion and migration ability were detected by transwell invasion assay and wound-healing assay. The messenger RNA level of BDNF was also detected by quantitative reverse transcriptase polymerase chain reaction; Western blot analysis was performed to assess pAKT expression.Expression of miR-204 is significantly down-regulated in an anoikis pattern. Restored expression level of miR-204 enables cells to acquire more sensitivity to anoikis and decrease invasive and metastatic behavior, and also results in BDNF down-expression and inhibits activation of mitochondria-dependent pathway through the PI3K/AKT signaling pathway leading to cancer cell anoikis in EOC cells.miR-204 up-regulation may be linked directly to the sensitivity of EOC cell anoikis by contributing to BDNF down-regulation. Our findings provide a novel mechanism for manipulating miR-204 levels therapeutically to restore anoikis sensitivity.