1. Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital. Fuzhou 350014, China.
2. Department of Blood Transfusion, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital. Fuzhou 350014, China.
Background: The incidence of endometrial carcinoma (EC) has been increasing annually, and treatment of advanced cases remains challenging. MicroRNA-424 (miR-424) was reported to affect several types of tumors, but its role in EC has not been studied.
Methods: We generated transient knockdown models of miR-424 and PTEN in EC cells. We measured mRNA and protein expression using RT-PCR and western blotting. We evaluated cell proliferation, invasion, migration, and apoptosis using CCK8, Transwell, wound healing, and flow cytometry assays. We also investigated the effect of miR-424 and PTEN on tumor growth using a metastatic tumor model in nude mice.
Results: The expression of miR-424 was significantly elevated in EC tissues and cell lines. MiR-424 inhibitor significantly restrained PTEN/PI3K/AKT signaling, while miR-424 mimic activated this pathway. Knockdown of PTEN significantly reversed the effects of miR-424 inhibitor on cell proliferation, invasion, migration, and apoptosis in EC cells. The significant inhibition of tumor growth and ki67 expression caused by miR-424 inhibitor were markedly promoted by sh-PTEN.
Conclusions: Our findings suggest that miR-424 inhibitor could inhibit cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) process, and tumor growth, while promoting apoptosis in EC. However, the effects of miR-424 inhibitor were markedly reversed by sh-PTEN. This study provides a potential novel therapeutic strategy for the prevention and treatment of EC by targeting miR-424.
Keywords: Endometrial carcinoma, miR-424, PTEN, AKT, PI3K