Hypoxia has been shown to be related to osteosarcoma development and progression. Pseudogene MSTO2P was reported to be dysregulated in hepatocellular carcinoma and lung cancer. However, the mechanism by which MSTO2P-modulated osteosarcoma remains unclear. MSTO2P and PD-L1 expression levels were examined by RT-qPCR and westernblot. Tumor cell invasion was determined by tranwell assay. EMT process was probed by determining E-cadherin and Vimentin levels. Soft agar assay was used to examine anchorage-independent growth of osteosarcoma cells. In vivo tumor growth was measured by xenografting tumor experiment. Hypoxia treatment promoted cell growth, invasion and EMT of osteosarcoma cells. MSTO2P knockdown led to attenuated cell growth, invasion and EMT of osteosarcoma cells under hypoxia condition. More interestingly, our data revealed that MSTO2P was positively associated with tumor growth in immunodeficient mice and human clinical tissues. PD-L1 was shown to act as a key effector for MSTO2P-regulated osteosarcoma progression under hypoxia condition. In conclusion, we unravel a novel mechanism for explaining MSTO2P-involved osteosarcoma progression under hypoxia condition, which will facilitate development of potential diagnostic and therapeutical strategies for osteosarcoma.

缺氧已被证明与骨肉瘤的发生和发展有关。据报道，假基因MSTO2P在肝细胞癌和肺癌中失调。但是，MSTO2P调节骨肉瘤的机制仍不清楚。通过RT-qPCR和westernblot检测MSTO2P和PD-L1表达水平。通过tranwell测定法确定肿瘤细胞侵袭。通过确定E-钙粘蛋白和波形蛋白的水平来探讨EMT过程。软琼脂试验用于检查骨肉瘤细胞的锚定非依赖性生长。通过异种移植肿瘤实验测量体内肿瘤生长。低氧治疗促进了骨肉瘤细胞的生长，侵袭和EMT。缺氧条件下，MSTO2P敲低导致骨肉瘤细胞的细胞生长，侵袭和EMT减弱。更有趣的是 我们的数据显示，MSTO2P与免疫缺陷小鼠和人类临床组织中的肿瘤生长呈正相关。在低氧条件下，PD-L1被证明是MSTO2P调节骨肉瘤进展的关键效应物。总之，我们揭示了一种在缺氧条件下解释MSTO2P参与的骨肉瘤进展的新机制，这将有助于开发潜在的骨肉瘤诊断和治疗策略。