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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

SIX1 reduces the expression of PTEN via activating PI3K/AKT signal to promote cell proliferation and tumorigenesis in osteosarcoma.


PMID 29807230

Abstract

Osteosarcoma is the most common form of primary malignant bone cancer which is most prevalent in children and adolescents. Dysregulated expressions of SIX1 and PTEN/PI3K/AKT have been demonstrated in bone malignancies including osteosarcoma. However, the mechanism of SIX1/PTEN/PI3K/AKT on osteosarcoma progression remains unknown. Therefore, this study aims to investigate the molecular mechanism of SIX1 and PTEN/PI3K/AKT on osteosarcoma progression. In this study, we first examined the expression of SIX1 and PTEN in human osteosarcoma tissues or blood samples and cell lines by immunohistochemistry, western blot analysis and qPCR. MTT, clone formation assay, wound healing assay, Transwell assay, in vivo tumorigenesis, flow cytometry and western blot were used to determine the function of SIX1/PTEN on cell proliferation, clone formation ability, migration, invasion, tumorigenesis, and cell apoptosis in SAOS2 and U2OS cells, respectively. Results showed that SIX1 was overexpressed in osteosarcoma tissues, blood samples and cell lines, whereas PTEN expression was reduced. SIX1 promoted cell growth, migration, invasion, and suppressed cell apoptosis. Up-regulation of SIX1 associated with reduced expression of PTEN and activation of PI3K/AKT signaling pathway. Down-regulated the expression of PTEN using gene transfer in U2OS and SAOS2 cells increased cell proliferation and inhibited cell apoptosis through activating PI3K/AKT signaling cascade. In addition, the tumorigenesis of U2OS and SAOS2 cells was suppressed when the cells were stably overexpressed SIX1 and PTEN simultaneously, compared with that in cells stably overexpressed SIX1 only. SIX1 promoted the progression of osteosarcoma via regulating PTEN/PI3K/AKT signaling cascade, which might provide a new potent therapeutic target for osteosarcoma.