1. MiR-205 inhibits cell apoptosis by targeting phosphatase and tensin homolog deleted on chromosome ten in endometrial cancer Ishikawa cells
- Author
-
Yue Li, Xinxin Hou, Meng Zhao, and Guiyu Zhang
- Subjects
Cancer Research ,PTEN ,Apoptosis ,Endometrium ,Endometrial cancer ,RNA interference ,Cell Line, Tumor ,microRNA ,Genetics ,Tensin ,Humans ,RNA, Messenger ,Protein kinase B ,3' Untranslated Regions ,PI3K/AKT/mTOR pathway ,Binding Sites ,biology ,Base Sequence ,PTEN Phosphohydrolase ,Endometrial Neoplasms ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,AKT pathway ,Oncology ,biology.protein ,Cancer research ,Female ,RNA Interference ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,Research Article - Abstract
Background MicroRNAs (miRNAs) are frequently dysregulated in human cancers and can act as either potent oncogenes or tumor suppressor genes. In the present study, we intend to prove that the gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a target gene of miR-205 and to investigate the suppressive effects on PTEN transcriptional activity by enhancing miR-205 expression in endometrial cancer Ishikawa cells. Methods Using Ishikawa cells as model systems, we up-regulated miR-205 expression by transient transfection with miR-205 mimics. A luciferase reporter assay, qRT-PCR and western blotting assays were used to verify whether PTEN is a direct target of miR-205. Meanwhile, the modulatory role of miR-205 in the AKT (protein kinase B) pathway was evaluated by determining the AKT phosphorylation. As a biological counterpart, we investigated cell apoptosis using flow cytometry. Results Our data indicate that miR-205 down-regulates the expression of PTEN through direct interaction with the putative binding site in the 3′-untranslated region (3′-UTR) of PTEN. Moreover, we documented the functional interactions of miR-205 and PTEN, which have a downstream effect on the regulation of the AKT pathway, explaining, at least in part, the inhibitory effects on Ishikawa cell apoptosis of enhancing miR-205 expression. Conclusions For the first time, we demonstrate that the expression of PTEN is directly regulated by miR-205 in endometrial cancer cells and leads the inhibition of cellular apoptosis. This relationship could be targeted for new therapeutic strategies for endometrial cancer.
- Published
- 2014