Abstract
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.
Highlights
Ovarian cancer, a type of malignancy in the ovary, is the most lethal gynaecological carcinoma as well as the fifth leading cause of cancer mortality among women [1]
The results show that 2,613 genes were significantly overexpressed in ovarian cancer tissues compared with normal ovarian tissues in the The Cancer Genome Atlas (TCGA) database and 1,378 survival significant genes were obtained through survival analyses
The survival plots suggested that the key genes significantly associated with overall survival and hazard ratio (HR) > 1 were cysteine-rich intestinal protein 1 (CRIP1) and PLEK2 (Figure 1(b))
Summary
A type of malignancy in the ovary, is the most lethal gynaecological carcinoma as well as the fifth leading cause of cancer mortality among women [1]. The main treatment options for epithelial ovarian cancer are tumour cell reduction surgery and platinum-based chemotherapy, immunotherapy, and targeted therapy. These therapeutic options are available, the overall five-year. The high mortality may be due to a number of factors, including the lack of symptoms and detectable biomarkers for ovarian cancer in its early stage, distant invasion, and metastasis [4, 5]. It is of great importance to identify new predictive biomarkers for early diagnosis and have a better understanding of the mechanism of ovarian cancer metastasis, which is an urgent issue for improving the efficacy of ovarian cancer treatment
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