PMID- 25962115 OWN - NLM STAT- MEDLINE DCOM- 20160407 LR - 20190221 IS - 1525-1438 (Electronic) IS - 1048-891X (Linking) VI - 25 IP - 6 DP - 2015 Jul TI - Up-Regulation of miR-204 Enhances Anoikis Sensitivity in Epithelial Ovarian Cancer Cell Line Via Brain-Derived Neurotrophic Factor Pathway In Vitro. PG - 944-52 LID - 10.1097/IGC.0000000000000456 [doi] AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. FAU - Yan, Hongliang AU - Yan H AD - *Hebei United University, Tangshan, PR China; daggerDepartment of Gynaecology, the Affiliated Hospital of the Chinese People's Armed Forces Logistic College, Tianjin, PR China; double daggerHealthy Care Center of Women and Children of Tianjin Beichen, Tianjin, PR China; section signBiomechanics Laboratory of Orthopaedic Research Institute of Tian Jin Hospital, Tianjin, China; and parallelHebei United University, Tangshan, PR China. FAU - Wu, Weiguang AU - Wu W FAU - Ge, Hongyu AU - Ge H FAU - Li, Pengfei AU - Li P FAU - Wang, Zheng AU - Wang Z LA - eng PT - Journal Article PL - England TA - Int J Gynecol Cancer JT - International journal of gynecological cancer : official journal of the International Gynecological Cancer Society JID - 9111626 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN204 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Anoikis/*genetics MH - Apoptosis MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/*metabolism MH - Carcinoma, Ovarian Epithelial MH - Cell Movement MH - Cell Proliferation MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - In Vitro Techniques MH - MicroRNAs/*genetics MH - Neoplasm Invasiveness MH - Neoplasms, Glandular and Epithelial/genetics/metabolism/*pathology MH - Ovarian Neoplasms/genetics/metabolism/*pathology MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Tumor Cells, Cultured MH - Up-Regulation EDAT- 2015/05/12 06:00 MHDA- 2016/04/08 06:00 CRDT- 2015/05/12 06:00 PHST- 2015/05/12 06:00 [entrez] PHST- 2015/05/12 06:00 [pubmed] PHST- 2016/04/08 06:00 [medline] AID - 10.1097/IGC.0000000000000456 [doi] PST - ppublish SO - Int J Gynecol Cancer. 2015 Jul;25(6):944-52. doi: 10.1097/IGC.0000000000000456.