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. However, its deliverance profile and biological function in osteosarcoma (OS) remain unclear. The 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. In 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). Taken together, the data of the present study demonstrate a novel molecular mechanism of MNAT1 involved in the formation of DDP resistance of OS cells.

中文翻译：

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MNAT1通过调节PI3K / Akt / mTOR途径促进骨肉瘤细胞增殖和对顺铂的化学耐药性

MNAT1（管理三叉戟1，MAT1）是一种细胞周期蛋白依赖性激酶激活激酶（CAK）复合物，在多种癌症中高度表达，并参与癌症分子的发病机理。然而，其在骨肉瘤（OS）中的递送特征和生物学功能仍不清楚。通过免疫印迹（WB）和免疫组化（IHC）检测MNAT1在OS中的表达。根据组织芯片（TMA）分析了MNAT1分子水平表达与OS临床预期之间的潜在关系。基于CCK8和OS细胞集落形成分析，评估了OS细胞的增殖潜力，同时采用了OS细胞穿透和原位组织来源伤口愈合分析来分析OS细胞的体外侵袭和迁移能力。裸鼠异种移植模型用于检测体内肿瘤生长。此外，进行了普通生物信息学分析和实验相关性验证，以研究MNAT1对OS的潜在调节机制。在这项研究中，我们发现并证实MNAT1在原位衍生的OS组织中明显过表达，而且，MNAT1的高表达与不良的临床期望密切相关。功能研究表明，MNAT1沉默可以减弱体外OS细胞的侵袭，迁移和增殖，并在体内抑制OS肿瘤的生长。机制研究表明，MNAT1通过PI3K / Akt / mTOR途径促进了OS进程。我们进一步证实，在调节OS对顺铂（DDP）的化学敏感性中需要MNAT1。在一起