Alteration of microRNA profiling in sphere‑cultured ovarian carcinoma cells

Abstract

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.

NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells

“…We observed an increased number of differentially expressed miRNAs in spheroid conditions than adherent conditions by miR-seq and noted similarities in the differential miRNA expression in our study with miRNAs expressed in other ovarian cancer models. The differential miRNA expression of two-dimensional adherent or three-dimensional spheroid culture conditions in an SKOV3-ipl model were previously reported [21]; their study identified 71 up-regulated and 63 down-regulated miRNAs. In that study, hsa-miR-34a-5p was up-regulated in 3D-sphere-cultured SKOV3-ipl cell lines, and we observed its upregulation in OV90 spheres.…”

MicroRNAs regulate granulosa cells apoptosis and follicular development — A review

“…An earlier bioinformatic analysis of miRNAs expression of FGCs showed that 139 associated pathways were screened out during the growth and selection of dominant follicles [ 69 ]. Furthermore, Cha et al 83 reported that 48 signal transduction pathways are up-regulated by miRNAs and 29 pathways are down-regulated by the miRNAs [ 80 ]. Nowdays, it has been clearly undetermined how many signal transduction pathways are involved in the miRNAs regulation roles [ 8 , 64 ].…”