eIF4E‑related miR‑320a and miR‑340‑5p inhibit endometrial carcinoma cell metastatic capability by preventing TGF‑β1‑induced epithelial‑mesenchymal transition

Zhang,Han‑Han; Li,Ran; Li,You‑Jie; Yu,Xin‑Xin; Sun,Qian‑Nan; Li,Ao‑Ying; Kong,Ying

doi:10.3892/or.2019.7437

eIF4E‑related miR‑320a and miR‑340‑5p inhibit endometrial carcinoma cell metastatic capability by preventing TGF‑β1‑induced epithelial‑mesenchymal transition

Authors:
- Han‑Han Zhang
- Ran Li
- You‑Jie Li
- Xin‑Xin Yu
- Qian‑Nan Sun
- Ao‑Ying Li
- Ying Kong
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Affiliations: Core Laboratory Glycobiol and Glycoengn, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Oncology, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China, Department of Biochemistry and Molecular Biology, Key Laboratory of Tumor Molecular Biology, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
Published online on: December 16, 2019 https://doi.org/10.3892/or.2019.7437
Pages: 447-460
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometrial cancer (EC) is a common form of cancer in women. Metastasis is the main cause of EC treatment failure. Eukaryotic translation initiation factor 4E (eIF4E) is an oncogene that is overexpressed in a variety of malignancies and their distant metastases. The present study analyzed microarray data from the Oncomine database and revealed that high eIF4E expression was associated with poor prognosis and high pathological grade of EC. The expression of eIF4E was higher in EC tissues compared with in adjacent normal tissues. In addition, microRNA (miR)‑320a and miR‑340‑5p expression levels were downregulated in EC tissues compared with those in adjacent normal tissues, which suggested that these microRNAs may serve as EC tumor suppressor genes. miR‑320a and miR‑340‑5p could bind to the 3'‑UTR of eIF4E mRNA, thus downregulating the expression of eIF4E and phosphorylated (p)‑eIF4E in EC cells. Overexpression of miR‑320a or miR‑340‑5p effectively suppressed HEC‑1A cell migration and invasion. The downregulation of eIF4E and p‑eIF4E following miR‑320a or miR‑340‑5p transfection reduced the invasiveness and metastatic capability of EC cells in a manner associated with decreased expression of matrix metallopeptidase (MMP)‑3 and MMP‑9. In addition, one of the effects of transforming growth factor β1 (TGF‑β1), which is to induce the phosphorylation of eIF4E, was suppressed by miR‑320a and miR‑340‑5p overexpression. These two microRNAs also attenuated the features of TGF‑β1‑induced epithelial‑mesenchymal transition (EMT). In conclusion, the results of the present study demonstrated that eIF4E was upregulated in EC, whereas miR‑320a and miR‑340‑5p were downregulated in EC compared with adjacent normal tissues. In vitro, miR‑320a and miR‑340‑5p inhibited the migratory capability of EC cells by downregulating MMP‑3 and MMP‑9 and prevented TGF‑β1‑induced EMT through p‑eIF4E.

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