Microrna-320a Acts As A Tumor Suppressor In Endometrial Carcinoma By Targeting Igf-1r

Dysregulation of microRNAs (miRs) is implicated in the carcinogenesis of various types of malignant tumor by manipulating cell growth and apoptosis. Abnormal expression of miR-320a is involved in tumorigenesis of many types of cancer. The potential association of miR-320a and the possible regulatory mechanisms in endometrial carcinoma is rarely elucidated. In the present study, it was demonstrated that miR-320a expression was decreased in endometrial carcinoma tissues and cell lines. The present results also indicated that overexpression of miR-320a suppressed cell proliferation through inducing G(2)/M phrase arrest and apoptosis. Insulin-like growth factor receptror-1 (IGF-1R) was verified to be the potential target of miR-320a by computational analysis and luciferase reporter assays. In addition, overexpression of miR-320a reduced endogenous IGF-1R expression in cells. Furthermore, it was demonstrated that upregulation of miR-320a inhibited phosphorylated (p)-protein kinase B and p-mechanistic target of rapamycin activation and promoted B cell lymphoma-2-associated death promoter expression. Reintroduction of IGF-1R into miR-320a-overexpressed cells antagonized the impact of miR-320a on its downstream protein, which demonstrated that the tumor suppressive role of miR-320a in endometrial carcinoma is exerted by the signal pathway mediated by IGF-1R. It was therefore concluded that miR-320a served an anti-tumor role on endometrial carcinoma through the regulation of IGF-1R, and miR-320a may be used as the target for the gene therapy of endometrial carcinoma.