Abstract
BackgroundMNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis. However, its deliverance profile and biological function in osteosarcoma (OS) remain unclear.MethodsThe expression of MNAT1 in OS was detected by western blot (WB) and immunohistochemistry (IHC). The potential relationship between MNAT1 molecular level expression and OS clinical expectations were analyzed according to tissues microarray (TMA). Proliferation potential of OS cells was evaluated in vitro based on CCK8 and OS cells colony formation assays, while OS cells transwell and in situ tissue source wound healing assays were employed to analyze the OS cells invasion and migration ability in vitro. A nude mouse xenograft model was used to detect tumor growth in vivo. In addition, ordinary bioinformatics analysis and experimental correlation verification were performed to investigate the underlying regulation mechanism of OS by MNAT1.ResultsIn this research, we found and confirmed that MNAT1 was markedly over-expressed in OS tissue derived in situ, also, highly MNAT1 expression was closely associated with bad clinical expectations. Functional studies had shown that MNAT1 silencing could weaken the invasion, migration and proliferation of OS cells in vitro, and inhibit OS tumor growth in vivo. Mechanism study indicated that MNAT1 contributed to the progression of OS via the PI3K/Akt/mTOR pathway. We further verified that the MNAT1 was required in the regulation of OS chemo-sensitivity to cisplatin (DDP).ConclusionsTaken together, the data of the present study demonstrate a novel molecular mechanism of MNAT1 involved in the formation of DDP resistance of OS cells.
Highlights
Menage a trois 1 (MNAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis
MNAT1 is highly expressed in OS cancer tissues and cell lines With the purpose of determining the expression of MNAT1 in the OS, we evaluated the expression of MNAT1 in tissues from patients diagnosed with OS and several cell lines as representative of OS
We uncovered that mRNA levels of MNAT1 were up-regulated in 30-paired OS cases and surrounding tissue not invaded by the tumor (Fig. 1c)
Summary
MNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis. Despite the great advances in comprehensive treatment of OS, prediction of early recurrence and metastasis is a big challenge for OS treatments [3, 4]. It is, an improved understanding of the molecular mechanism of OS tumorigenesis may open up new avenues to develop novel therapeutic approaches for OS. Mounting evidence has revealed that MNAT1 play a pivotal part in regulation of biological characteristics of cancer cells. The underlying mechanism of MNAT1 in OS have not been well documented yet
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