Abstract

BackgroundSeveral studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. However, the function and expression of miR-501 in endometrial cancer (EC) remain obscure.MethodsThe expression of miR-501 was determined using quantitative real-time PCR. MTT assay, colony formation assay and cell cycle analysis were used to evaluate the proliferation ability. Migration and invasion were assessed using transwell assay. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501.ResultsIn this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. High expression of miR-501 was also found in the copy-number-high group than other groups. Moreover, in vitro and in vivo assay showed that overexpression of miR-501 can promote proliferation and metastasis. Mechanistically, we found that miR-501 promotes tumor progression by directly targeting HOXD10. Further study also indicated that miR-501 overexpression can activate the AKT/mTOR pathway.ConclusionsMiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer.

Highlights

  • Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers

  • MiR‐501 expression is increased in human endometrial cancer (EC) patients and its high expression predicts poor survival In our previous study, we found several miRNAs that showed differential expression between endometrial tissues and benign endometrium, which included miR-501 [14]

  • High expression of miR-501 is associated with pelvic lymph node metastasis and shorter overall survival

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Summary

Introduction

Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. The function and expression of miR-501 in endometrial cancer (EC) remain obscure. Methods: The expression of miR-501 was determined using quantitative real-time PCR. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501. Results: In this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. Conclusions: MiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer. All the data reflect the need for a more comprehensive understanding of the molecular genetics of endometrial cancer, especially for high grade ECs

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