Cha Hwa Jun, An Sung Kwan, Kim Tae Jin, Lee Jae Ho
Department of Beauty Care and Cosmetics, Osan University, Osan, Gyeonggi 18119, Republic of Korea.
Molecular-Targeted Drug Research Center, Konkuk University, Seoul 05029, Republic of Korea.
Oncol Lett. 2018 Aug;16(2):2016-2022. doi: 10.3892/ol.2018.8818. Epub 2018 May 25.
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.
卵巢癌是一种侵袭性和致命性癌症，部分原因可归结于在疾病进展早期有效检测方面存在的并发症。上皮性卵巢癌常扩散至腹腔并形成多细胞聚集体。这种独特的早期转移事件以及多细胞聚集体的形成被认为是理解卵巢癌转移潜在分子机制的基础。因此，本研究建立了一种三维（3D）球体培养系统来模拟卵巢癌的后期阶段。本研究的目的是调查在各种癌症模型中具有转移和化疗耐药功能的微小RNA（miRNA）在卵巢癌细胞中是否会因三维（3D）培养而发生改变。使用3D球体培养系统生成了SKOV3ip1卵巢癌细胞的多细胞聚集体。细胞活力分析表明，与传统二维（2D）单层培养的SKOV3ip1系统中的细胞相比，球体培养的SKOV3ip1细胞表现出化疗耐药性。在相同实验条件下，在3D球体培养的SKOV3ip1细胞中鉴定出71个上调的miRNA和63个下调的miRNA。使用PITA、microRNAorg和TargetScan进一步鉴定了3D球体培养特异性miRNA的预测靶标。与靶基因库和京都基因与基因组百科全书通路相比，本研究提供了证据表明3D球体培养特异性miRNA调节了3D球体培养的SKOV3ip1细胞中的球体形成和化疗耐药性。总体而言，本研究结果表明miRNA介导的调节与SKOV3ip1多细胞聚集的特征有关，包括球体形成和化疗耐药性。
