LncRNA DLEU1 Contributes To Ovarian Carcinoma Tumorigenesis And Development By Interacting With MiR-490-3p And Altering CDK1 Expression

Background:Recently,a large number of studies have focused on the important role of long non-coding RNAs(lncRNAs)in metabolism and development,and have found that abnormal lncRNA expression is associated with the pathogenesis and development of many diseases.The lncRNA DLEU1 is involved in many solid tumors and hematological malignancies.However,its role in epithelial ovarian carcinoma(EOC)and the associated molecular mechanisms has not been reported.Methods:The expression level of lncRNA DLEU1 in normal ovarian tissue,ovarian benign tumor tissue,ovarian borderline tumor tissue and epithelial ovarian cancer tissue was detected by quantitative reverse transcription PCR(qRT-PCR).The expression of LncRNA DLEU1 was up-regulated by plasmid transfection in ovarian cancer cells A2780 and OVCAR3,and the expression of LncRNA DLEU1 was silenced by siRNA.The proliferation of ovarian cancer cells was detected by MTT cell proliferation assay.The expression of ovarian cancer cells was up-regulated/down-regulated./ Silencing LncRNA DLEU1 expression of ovarian cancer cells after apoptosis;cell scratches and Transwell assay to detect changes in migration and invasion of ovarian cancer cells.The effect of up-regulation of LncRNA DLEU1 on the tumorigenic ability of A2780 cells was verified by nude mouse xenograft.The effect of LncRNA DLEU1 expression on ovarian cancer genotype was detected by Weastern blot.Immunohistochemistry and PCR confirmed the possible molecular mechanism of LncRNA DLEU1 influencing the biological behavior of ovarian cancer.Results : In the present study,quantitative reverse transcription–PCR(qRT-PCR)demonstrated higher lncRNA DLEU1 expression in EOC tissues than in normal tissues.Plasmid transfection of LncRNA DLEU1 to upregulate its expression in the ovarian cancer cell lines A2780 and OVCAR3 increased cell proliferation,migration,and invasion while inhibited apoptosis.Nude mouse xenograft showed that LncRNA DLEU1 overexpression promoted tumor growth in vivo.QRT-PCR showed decreasedmiR-490-3p expression,while western blotting demonstrated increased its target genes CDK1,as well as MMP2,Bcl-xL,and P70S6 K protein expression,respectively.Short interfering RNA silencing of LncRNA DLEU1 produced opposite results,where qRT-PCR showed increased miR-490-3p expression.The dual luciferase reporter assay revealed a direct interaction between LncRNA DLEU1 and miR-490-3p.MiR-490-3p plays a tumor suppressor role in epithelial ovarian cancer by targeting CDK1 regulation.Conclusion:Therefore,we suggest that through interaction with miR-490-3p,LncRNA DLEU1 may influence the expression of CDK1 protein,subsequently promoting the development and progression of EOC.