MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R

Tu,Chunhua; Wang,Fen; Wan,Junhui

doi:10.3892/mmr.2017.8288

MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R

Authors:
- Chunhua Tu
- Fen Wang
- Junhui Wan
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Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: December 18, 2017 https://doi.org/10.3892/mmr.2017.8288
Pages: 4090-4098

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Abstract

Endometrial carcinoma (EC) is the sixth most common type of malignant tumor occurring in females. MicroRNAs (miRNAs) serve as oncogenes or tumor suppressors in human cancer and play important roles in tumorigenesis, and tumor development by regulating various processes. Thus, further investigation into miRNAs involved in EC formation and progression may aid in developing effective therapeutic strategies for patients with this disease. miRNA‑381 (miR‑381) is aberrantly expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanisms of miR‑381 in EC are poorly understood. In the present study, the results showed that miR‑381 was downregulated in EC tissues and cell lines. Decreased miR‑381 expression correlated with the International Federation of Gynecology and Obstetrics stage, lymph nodes metastasis and myometrial invasion of EC. The ectopic expression of miR‑381 significantly inhibited the proliferation and invasion of EC cells. Through a series of experiments, the insulin‑like growth factor receptor 1 (IGF‑1R) was identified as a novel direct target of miR‑381 in EC. Furthermore, IGF‑1R was highly expressed in EC tissues and inversely correlated with miR‑381 levels. IGF‑1R overexpression partially abrogated the tumor‑suppressive effects of miR‑381 on the proliferation and invasion of EC cells. miR‑381 targeted IGF‑1R to inactivate the protein kinase B (AKT) and extracellular signal‑regulated kinase (ERK) signaling pathways in EC. These results suggest that miR‑381 acts as a tumor suppressor in EC by directly targeting IGF‑1R, and indirectly regulating the AKT and ERK signaling pathways. Thus, miR‑381 should be investigated as a prognostic biomarker and novel therapeutic target for the treatment of patients with EC.

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