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Tao Wang,* Zhi-Yong Wang,* Ling-Yuan Zeng, Yao-Zu Gao, Yu-Xin Yan, Quan Zhang Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Wang Tel +86-0351-3363078Email shanxiwangtao0912@163.comObjective: The goal of our present study was to explore the expression level, biological function, and underlying molecular mechanism of ribosomal protein s21 (RPS21) in human osteosarcoma (OS).Methods: Firstly, we evaluated the expression of RPS21 in OS tissue samples based on the Gene Expression Omnibus (GEO) datasets and also measured the RPS21 expression of OS cell lines (MG63, and U2OS) by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA interference method was used to reduce the expression of RSP21 in the OS cells. Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, and transwell assays were conducted to measure the proliferation, migration, and invasion of OS cells. The mitogen-activated protein kinase (MAPK) pathway-related proteins levels were examined by Western blot.Results: Our analyses showed that the expression of RPS21 was significantly increased in OS, compared with normal samples. Upregulation of RPS21 was associated with worse outcomes of OS patients. Knockdown of RPS21 suppressed OS cell proliferation, colony-forming ability, migration, and invasion capacities. Moreover, down-regulation of RPS21 inactivated the MAPK signaling pathway.Conclusion: RPS21 plays an oncogenic candidate in OS development via regulating the activity of MAPK pathway; therefore, it may serve as a novel therapeutic target for OS treatment.Keywords: RPS21, MAPK pathway, osteosarcoma, viability, migration

Hong-Mei Liu,1,2,* Ya-Fei Zhang,1,2,* Yan-Dong Xie,1,2 Yi-Fan Cai,1,2 Bai-Yang Li,1,2 Wen Li,3 Ling-Yu Zeng,4 Yu-Ling Li,4 Ru-Tong Yu1,2 1Department of Neurosurgery, Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 2Department of Neurosurgery, Institute of Nervous System Diseases, Xuzhou Medical University, 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, 4Department of Chemistry, School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'1,O1-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy. Keywords: hypoxia responsive, cellular uptake, siRNA delivery, ionizable liposome, hypoxic conditions