Expression And Correlation Study Of MiR-93-3p And MiR-497-5p In Chemotherapy-resistant Epithelial Ovarian Cancer Tissues

Objective:In this study,the expression of miR-93-3p and miR-497-5p in epithelial ovarian cancer was studied to analyze the clinical significance of miR-93-3p and miR-497-5p in epithelial ovarian cancer and the differences in expression between chemotherapy resistant and sensitive tissues.The target genes of miR-93-3p and miR-497-5p were predicted and analyzed by using two bioinformatics analysis software and combined with literature data to preliminarily investigate the role of miR-93-3p and miR-497-5p in the chemotherapy resistance of epithelial ovarian cancer,so as to control the potential candidate genes of the chemotherapy resistance of epithelial ovarian cancer.Methods:Tissue samples of 111 patients with epithelial ovarian cancer in shanxi cancer hospital were collected and divided into two groups: chemotherapy resistance group and chemotherapy sensitivity group(control group)according to the clinical practice guidelines of ovarian cancer published by NCCN.RT-PCR was used to detect the relative expression of miR-93-3p and miR-497-5p in epithelial ovarian cancer tissues,and to analyze the relationship between the relative expression of miR-93-3p and miR-497-5p and clinicopathological characteristics and its correlation with chemotherapy resistance.GO annotation and KEGG pathway analysis of the predicted target genes of miR-93-3p and miR-497-5p were carried out by bioinformatics method,and literature was consulted to predict the possible target genes of miR-93-3p and miR-497-5p in the course of chemotherapy resistance of epithelial ovarian cancer.RT-PCR was used to detect and predict the expression differences of target genes in the chemotherapy-resistant and sensitive groups.Western-blot was used to further detect the expression of the predicted target genes in the two groups.Spearman rank was used to analyze the correlation between miR-93-3p and miR-497-5p with the predicted target genes.The possible target genes and related signaling pathways of miR-93-3p and miR-497-5p in the development of epithelial ovarian cancer were comprehensively analyzed.Results:1、In epithelial ovarian cancer,the expression of miR-93-3p and miR-497-5p decreased progressively with the increase of surgical clinical stage and histological grade.In combination with or without lymphatic metastasis,the expression level of miR-93-3p and miR-497-5p in lymphatic metastases was significantly lower than that in non-lymphatic metastases.It was suggested that miR-93-3p and miR-497-5p were associated with the development of epithelial ovarian cancer.2、The expression level of miR-93-3p and miR-497-5p in the chemotherapy resistant group of epithelial ovarian cancer was significantly lower than that in the chemotherapy sensitive group,suggesting that miR-93-3p and miR-497-5p was correlated with the chemotherapy-resistant group of epithelial ovarian cancer.3、According to bioinformatics software analysis and literature summary,the potential target genes involved in the chemotherapy resistance of miR-93-3p and miR-497-5p in epithelial ovarian cancer were CDC42 and Wnt3 a.4、CDC42 mRNA and Wnt3 a mRNA expression in chemotherapy-resistant tissues of epithelial ovarian cancer was significantly higher than that in chemotherapy-sensitive tissues.5、CDC42 protein expression levels and Wnt3 a protein expression levels inepithelial ovarian cancer were detected by weston-blot assay and the expression differences between the chemotherapy-resistant group and the sensitive group were compared.Compared with the chemotherapy-sensitive group of epithelial ovarian cancer,the relative expression of CDC42 protein and Wnt3 a protein in the chemotherapy resistant group was significantly increased.6、Spearman grade analysis showed that the expressions of miR-93-3p and CDC42 mRNA,mir-497-5p and Wnt3 a mRNA in epithelial ovarian cancer were negatively correlated.Conclusion:1、MiR-93-3p and miR-497-5p are associated with the development of epithelial ovarian cancer.2、MiR-93-3p and miR-497-5p were associated with chemotherapy resistance in epithelial ovarian cancer.3、CDC42 mRNA and Wnt3 a mRNA were associated with the development of chemotherapy resistance in epithelial ovarian cancer.4、MiR-93-3p and miR-497-5p may be involved in the chemotherapy resistance process of epithelial ovarian cancer through negative regulation of target genes CDC42 and Wnt3a respectively.