Microrna-590-5p Promotes Cell Survival In Endometrioid Endometrial Cancer By Suppressing Tumor Suppressor Pten
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2017)
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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