The Role Of Long Non-Coding RNA PCA3 In Epithelial Ovarian Carcinoma Tumorigenesis And Progression

Objective: Ovarian cancer is the fifth leading cause of cancer death in women.It is one of the most deadly gynecologic malignancies in the world.Due to delayed diagnosis,tumor recurrence and chemotherapy resistance,the 5-year survival rate of advanced ovarian cancer is about 30%.Therefore,there is an urgent need to explore new ways to diagnose,prognose and treat targets for ovarian cancer.In recent years,there has been increasing evidence that long non-coding RNAs play an important role in regulating epigenetic,transcriptional,and post-transcriptional gene expression,and are involved in the development of many diseases such as tumors.It has been reported that lncRNA PCA3 plays a cancer-promoting role in prostate cancer and chronic myeloid leukemia.However,in ovarian cancer,the function of lncRNA PCA3 is unclear.This study aimed to explore the role of lncRNA PCA3 in ovarian cancer and its specific mechanism.Methods: The expression of lncRNA PCA3 was detected in ovarian cancer and normal ovarian tissues,and the expression of lncRNA PCA3 was detected in ovarian cancer cell lines A2780,OVCAR3,CAOV3,SKOV3.The lncRNA PCA3 was knocked down in a highly expressed ovarian cancer cell line,and the expression of si-lncRNA PCA3 on ovarian cancer cell phenotype and related molecules was detected by cell proliferation assay,apoptosis assay,cell migration and cell invasion assay.The downstream binding miRNA of lncRNA PCA3 was predicted by the bioinformatics prediction site,and the dual luciferase reporter gene was used to detect lncRNA PCA3 and predict whether the target gene binds.Western Blotting was used in ovarian cancer cell lines to detect the effect of lncRNA PCA3 on downstream proteins regulated by target genes.Results: We found that lncRNA PCA3 is relatively highly expressed in ovarian cancer compared to normal ovarian tissue.In ovarian cancer cell lines,lncRNA PCA3 expression of A2780 and OVCAR3 was higher than that of CAOV3 and SKOV3.Knockdown of lncRNA PCA3 in epithelial ovarian cancer cell lines A2780 and OVCAR3 by siRNA significantly inhibited cell proliferation,migration and invasion,and promoted apoptosis.Bioinformatics prediction and dual luciferase reporter assaysindicate that the 3'UTR of lncRNA PCA3 has a potential binding site for miR-106b-5p.In addition,knockdown of lncRNA PCA3 also reduced protein expression of Ras homologous gene family members C(RhoC),Bcl / xl,P70 ribosomal S6 kinase(P70S6K)and matrix metalloproteinase 2(MMP2)regulated by miR-106 b.Conclusion: The results suggest that lncRNA PCA3 may inhibit the inhibition of downstream regulatory gene RhoC by binding to miR-106 b,thereby promoting the development of epithelial ovarian cancer.