Objective. To explore the expression, functions, and the possible mechanisms of cysteine-rich intestinal protein 1 (CRIP1) in epithelial ovarian cancer. Methods. Using open microarray datasets from The Cancer Genome Atlas (TCGA), we identified the tumorigenic genes in ovarian cancer. Then, we detected CRIP1 expression in 26 pairs of epithelial ovarian cancer tissue samples by immunohistochemistry (IHC) and performed a correlation analysis between CRIP1 and the clinicopathological features. In addition, epithelial ovarian cancer cell lines A2780 and OVCAR3 were used to examine CRIP1 expression by western blot and qRT-PCR. Various cell function experiments related to tumorigenesis were performed including the CCK8 assay, EdU, Annexin V-FITC/PI apoptosis assay, wound healing, and Transwell assay. In addition, the expression of epithelial-mesenchymal transition (EMT) markers was detected by western blot to illustrate the relationship between CRIP1 and EMT. Furthermore, KEGG pathway enrichment analysis and western blot were conducted to reveal the signaling pathways in which CRIP1 is involved in ovarian cancer pathogenesis. Results. CRIP1 was identified as an oncogene from the TCGA database. The IHC score demonstrated that the CRIP1 protein was expressed at a higher level in tumours than in tumour-adjacent tissues and was associated with a higher pathological stage, grade, and positive lymphatic metastasis. In cell models, CRIP1 was overexpressed in serous epithelial ovarian cancer. Cell function experiments showed that the knockdown of CRIP1 did not significantly affect cell proliferation or apoptosis but could exert an inhibitory effect on cell migration and invasion, and also induce changes in EMT markers. Furthermore, KEGG pathway enrichment analysis and western blot showed that CRIP1 could induce ovarian cancer cell metastasis through activation of the Wnt/β-catenin pathway. Conclusion. This study is the first to demonstrate that CRIP1 acts as an oncogene and may promote tumour metastasis by regulating the EMT-related Wnt/β-catenin signaling pathway, suggesting that CRIP1 may be an important biomarker for ovarian cancer metastasis and progression.

中文翻译：

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富含半胱氨酸的肠蛋白 1 通过促进 Wnt/β-连环蛋白介导的 EMT 和肿瘤转移作为上皮性卵巢癌标志物

客观。探讨富含半胱氨酸的肠蛋白1（CRIP1）在上皮性卵巢癌中的表达、功能及其可能机制。方法. 使用来自癌症基因组图谱 (TCGA) 的开放微阵列数据集，我们确定了卵巢癌中的致瘤基因。然后，我们通过免疫组织化学（IHC）检测了 26 对上皮性卵巢癌组织样本中 CRIP1 的表达，并对 CRIP1 与临床病理特征进行了相关性分析。此外，上皮性卵巢癌细胞系 A2780 和 OVCAR3 用于通过蛋白质印迹和 qRT-PCR 检测 CRIP1 的表达。进行了与肿瘤发生相关的各种细胞功能实验，包括 CCK8 测定、EdU、Annexin V-FITC/PI 凋亡测定、伤口愈合和 Transwell 测定。此外，通过蛋白质印迹检测上皮 - 间质转化（EMT）标志物的表达，以说明CRIP1与EMT之间的关系。此外，结果。CRIP1 被鉴定为来自 TCGA 数据库的致癌基因。IHC 评分表明，CRIP1 蛋白在肿瘤中的表达水平高于在肿瘤邻近组织中的表达，并且与更高的病理分期、分级和阳性淋巴转移相关。在细胞模型中，CRIP1 在浆液性上皮性卵巢癌中过度表达。细胞功能实验表明，敲低CRIP1对细胞增殖或凋亡没有显着影响，但对细胞迁移和侵袭有抑制作用，还会诱导EMT标志物的变化。此外，KEGG通路富集分析和western blot显示CRIP1可以通过激活Wnt/ β -catenin通路诱导卵巢癌细胞转移。结论. 本研究首次证明CRIP1作为癌基因可能通过调节EMT相关的Wnt/ β -catenin信号通路促进肿瘤转移，提示CRIP1可能是卵巢癌转移和进展的重要生物标志物。