Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai, 200072, China.
J Transl Med. 2022 May 10;20(1):201. doi: 10.1186/s12967-022-03404-9.
As a common complication of epithelial ovarian cancer (EOC), malignant ascites contributes to the peritoneal metastasis of EOC. CircRNAs play essential roles in tumor metastasis. However, no circRNAs have been reported to be involved in EOC peritoneal metastasis via ascites.
Total of 22 samples from 9 EOC patients containing primary lesions (T), tumor cells from ascites (ASC), and metastatic lesions (M) were included for RNA sequencing to identify differentially expressed circRNAs and mRNAs among different tumors. Bioinformatic analyses, including single-sample Gene Set Enrichment Analysis and soft cluster analysis, were performed to find circRNAs potentially correlated with ascitic metastasis. Wound healing and transwell analysis were performed to evaluate tumor cells metastasis in vitro. Quantitative real-time PCR and western-blot were used for gene expression evaluation.
According to transcriptomic analysis, ASC showed mesenchymal phenotype while T and M showed epithelial phenotype. 10 circRNAs were differentially expressed among ASC, T, and M. Among them, hsa_circ_0000497 and hsa_circ_0000918 were significantly up-regulated in ASC. Functional analysis showed that both hsa_circ_0000497 and hsa_circ_0000918 promoted metastasis of EOC via epithelial-mesenchymal transition (EMT) in vitro. The regulatory network construction identified 8 miRNAs and 19 mRNAs, and 7 miRNAs and 17 mRNAs as potential downstream target genes of hsa_circ_0000497 and hsa_circ_0000918, respectively, which may play pivotal roles in EOC ascitic metastasis.
circRNAs (hsa_circ_0000497 and hsa_circ_0000918) contribute to metastasis of EOC via ascites by regulating EMT. These circRNAs may serve as novel potential therapeutic targets or prognostic biomarkers for EOC peritoneal metastasis.
作为上皮性卵巢癌（EOC）的常见并发症，恶性腹水促进了 EOC 的腹膜转移。CircRNAs 在肿瘤转移中发挥着重要作用。然而，目前还没有报道表明 CircRNAs 参与了通过腹水的 EOC 腹膜转移。
共纳入 9 名 EOC 患者的 22 个样本，其中包含原发性病变（T）、腹水（ASC）中的肿瘤细胞和转移性病变（M），用于 RNA 测序以鉴定不同肿瘤之间差异表达的 circRNAs 和 mRNAs。进行生物信息学分析，包括单样本基因集富集分析和软聚类分析，以寻找与腹水转移潜在相关的 circRNAs。进行划痕愈合和 Transwell 分析以评估肿瘤细胞在体外的转移。使用定量实时 PCR 和 Western blot 进行基因表达评估。
根据转录组分析，ASC 表现出间充质表型，而 T 和 M 表现出上皮表型。在 ASC、T 和 M 之间，有 10 个 circRNAs 表达差异。其中，hsa_circ_0000497 和 hsa_circ_0000918 在 ASC 中显著上调。功能分析表明，hsa_circ_0000497 和 hsa_circ_0000918 均通过体外上皮-间充质转化（EMT）促进 EOC 的转移。调控网络构建确定了 8 个 miRNA 和 19 个 mRNAs，以及 7 个 miRNA 和 17 个 mRNAs 分别为 hsa_circ_0000497 和 hsa_circ_0000918 的潜在下游靶基因，它们可能在 EOC 腹水转移中发挥关键作用。
circRNAs（hsa_circ_0000497 和 hsa_circ_0000918）通过调节 EMT 促进 EOC 通过腹水转移。这些 circRNAs 可能作为 EOC 腹膜转移的新型潜在治疗靶点或预后生物标志物。
