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• W2984453609 abstract "Dysregulation of microRNA-618 (miR-618) has been observed in multiple types of human cancer. However, whether miR-618 is implicated in osteosarcoma (OS) initiation and progression is still unclear. Hence, we measured the expression of miR-618 in OS tissues and cell lines. In addition, the roles of miR-618 and the mechanisms underlying its activities in OS cells were examined.The expression status of miR-618 in OS was analyzed by reverse-transcription quantitative PCR. The regulatory roles of miR-618 overexpression in OS were explored by the Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell cell migration and invasion assays, and a tumor xenograft experiment.The results revealed that the expression of miR-618 was notably lower in OS tissues and cell lines, and that the low miR-618 expression significantly correlated with the clinical stage and distant metastasis among patients with OS. Exogenous miR-618 expression significantly suppressed OS cell proliferation, migration, and invasion and induced apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation indicated that metadherin (MTDH) is a direct target gene of miR-618 in OS cells. A knockdown of MTDH mimicked the tumor-suppressive effects of miR-618 upregulation on OS cells. Notably, resumption of MTDH expression attenuated the miR-618-mediated reduction in OS cell growth and metastasis in vitro. In addition, miR-618 overexpression reduced the PTEN-AKT pathway output in OS cells both in vitro and in vivo through downregulation of MTDH.To the best of our knowledge, this is the first study to show that miR-618 exerts crucial tumor-suppressive actions in OS pathogenesis by directly targeting MTDH mRNA and reducing PTEN-AKT pathway output. These results will help to elucidate the functions of miR-618 in OS and suggest that this miRNA may be investigated as a therapeutic target in this disease." @default.
• W2984453609 created "2019-11-22" @default.
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• W2984453609 date "2019-11-01" @default.
• W2984453609 modified "2023-10-18" @default.
• W2984453609 title "<p>MicroRNA-618 Directly Targets Metadherin mRNA To Suppress The Malignant Phenotype Of Osteosarcoma Cells By Reducing PTEN-AKT Pathway Output</p>" @default.
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• W2984453609 doi "https://doi.org/10.2147/ott.s219440" @default.
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