MicroRNA-873 Affects The Proliferation And Invasion Of Endometrial Cancer Cells By Directly Targeting Hepatoma-derived Growth Factor

Objective:Accumulating evidence has well documented that the abnormal microRNA(miRNA)expression is a hallmark of cancer,including endometrial cancer(EC).The dysregulation of miRNAs may play important roles in the development and progression of EC through participating in the regulation of multiple aggressive behaviors.Thus,an in-depth understanding of the specific miRNAs related with EC initation and progression might be crucial for exploring attractive therapeutic techniques.However,the expression status and regulatory roles of miR-873 have yet to be elucidated in EC.Hence,this study was attempted to detect miR-873 and its direct target gene HDGF expression in EC and investigate the biological functions of miR-873 and HDGF in EC progression as well as to its underlying mechanisms.The purpose of the study was to elucidate the function of miR-873 in the endometrial cancer and the mechanisms regulating its direct target gene HDGF in these processes.Methods:Quantitative RT-PCR was carried out to compare the expression of miR-873 between endometrial carcinoma tissues and adjacent normal endometrial tissues.Endometrial cancer cells were cultured and transfected with miR-873 mimics,then the effects of miR-873 on cell proliferation and cell invasion were observed by transwell method and CKK-8 method.The target gene of miR-873 was predicted by bioinformatics software,and HDGF was found to be its potential target gene,which was verified by a dual-luciferase reporter assay.Quantitative RT-PCR and the Western Blot method were used to detect the expression of miR-873 and its potential target gene HDGF in endometrial cancer,and the relationship between HDGF and miR-873 was analyzed.Result:In the present study,miR-873 expression was downregulated in EC tissues and cell lines.Decreased miR-873 expression was significantly correlated with the FIGO stage and lymph node metastasis of EC patients.Functional assays observed that resumed of miR-873 expression suppressed the proliferation and invasion of EC cells.Additionally.hepatoma-derived growth factor(HDGF)was verified as a direct target gene of miR-873 in EC cells.HDGF was highly expressed in EC tissues,and inversely correlated with that of miR-873 expression.Furthermore,HDGF silencing could imitate the tumor-suppressing activity of miR-873 overexpression in EC cells.Finally,a series of rescue experiments identified that recovered HDGF expression hindered the anti-proliferative and anti-invasive roles of miR-873 upregulation in EC cells.Conclusion:This study indicated that miR-873 has an important role as a tumor suppressor gene in the development of EC by directly targeting HDGF.These findings may provide novel insights for clinical treatments to prevent the aggressive behaviors of EC.