Alteration of microRNA profiling in sphere-cultured ovarian carcinoma cells.

Abstract

Ovarian cancer is an aggressive and lethal cancer, which in part, can be attributed to complications in the effective detection of this disease during early stages of progression. Frequently, epithelial ovarian cancer is disseminated to the abdominal cavity and forms multicellular aggregates. This unique early metastatic event, and formation of the multicellular aggregate is implicated to provide a basis for understanding the underlying molecular mechanisms of metastasis in ovarian cancer. Therefore, a 3-dimensional (3D) sphere culture system was established in the present study to mimic the later stages of ovarian cancer. The aim of the present study was to investigate whether microRNAs (miRNAs), which have functions in metastasis and chemoresistance in various cancer models, are altered in ovarian cancer cells by 3-dimensional (3D) culture. A multicellular aggregate of SKOV3ip1 ovarian carcinoma cells was generated using a 3D sphere culture system. Cell viability analysis demonstrated that the sphere-cultured SKOV3ip1 cells exhibited chemoresistance compared with those in a conventional 2-dimensional (2D) monolayer cultured SKOV3ip1 system. Under the same experimental conditions, 71 upregulated miRNAs and 63 downregulated miRNAs were identified in the 3D sphere-cultured SKOV3ip1 cells. The predicted targets of the 3D sphere-culture specific miRNAs were further identified using PITA, microRNAorg and TargetScan. Compared with the target gene pool and Kyoto Encyclopedia of Genes and Genomes pathway, the present study provides evidence that the 3D sphere culture-specific miRNAs regulated sphere formation and chemoresistance in 3D sphere-cultured SKOV3ip1 cells. Overall, the results of the present study demonstrated that miRNA-mediated regulation is implicated to provoke features of SKOV3ip1 multicellular aggregation, including sphere formation and chemoresistance.