Microrna-590-5p Promotes Cell Survival In Endometrioid Endometrial Cancer By Suppressing Tumor Suppressor Pten

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2017)

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Abstract
MicroRNAs (miRNAs) are known to be dysregulated in many tumors and associated with aggressive or poor prognosis phenotypes. miR-590-5p acts as an oncogene in a variety of human malignancies. However, its mechanism of action in endometrioid endometrial cancer (EEC) is poorly understood. In this study, we performed qRT-PCR to detect the miR-590-5p expression in EEC tissues, and found that miR-590-5p expression levels were significantly upregulated in EEC tissue specimens compared with the noncancerous endometrial tissues. Subsequently, we confirmed that knockdown of miR-590-5p inhibits cell proliferation, and induces cell cycle arrest and apoptosis, and activates the intrinsic apoptotic pathway including upregulating cleaved-caspase-3, Bax and cleaved-PARP. Most importantly, we identified that miR-590-5p inhibits phosphatase and tensin homolog (PTEN), a tumor suppressor gene by directly targeting its 3'-UTR. Meanwhile, our data showed that PTEN level in the cancer tissues was inversely correlated with miR-590-5p expression in 20 EEC patients. Furthermore, the tumor suppressive effects of miR-590-5p downregulation were rescued by knockdown of PTEN in EEC cells. These results demonstrated that miR-590-5p acts as an oncogene and positively regulates EEC cells by targeting PTEN, suggesting that suppression of miR-590-5p may be a novel approach for the treatment of EEC.
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Key words
miR-590-5p, endometrioid endometrial cancer, proliferation, apoptosis, cell cycle, PTEN
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