Skp2高表达与骨肉瘤患者新辅助化疗耐药之间的联系

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Abstract Objective To explore the effect of Skp2 in neoadjuvant chemotherapy resistance of osteosarcoma. Methods Gene expression profiles of osteosarcoma and resistant osteosarcoma were collected from GSE126209, GSE16089 and TCGA datasets. The mechanisms of Skp2 resistance to osteosarcoma were identified. From February 2018 to June 2019, 17 patients with osteosarcoma admitted to the Third Clinical Medical College of Xinjiang Medical University were collected, non-drug resistance was defined as tumor cell necrosis rate (TCNR) ≥90%, and drug resistance was defined as TCNR < 90%, 11 cases of including non-drug resistant tumor tissues and 6 cases of drug resistant tumor tissues; 11 cases of non-drug-resistant paracancer tissues and 6 cases of drug-resistant paracancer tissues. RT-qPCR and Western-blot were used to detect mRNA and protein expression of Skp2 and related genes in osteosarcoma carcinoma tissues and adjacent tissues. Results The Skp2 was up-regulated in both osteosarcoma tissue and Methotrexate resistant cells. It was involved in cell cycle and FOXO pathway. Molecular experimental results showed that Skp2 and AKT expressions in drug-resistant osteosarcoma tissues were significantly increased (P ＜ 0.05); the expressions of p27, FOXO1 and E-Cadherin in resistant osteosarcoma were significantly lower (P ＜ 0.05). Cox analysis indicated that Skp2 (HR = 1.52, 95%CI: 0.67-3.46, P = 0.31), AKT (HR = 1.04, 95%CI: 0.48-2.28, P = 0.93), p21 (HR = 1.09, 95%CI: 0.51-2.34, P = 0.83), p27 (HR = 1.50, 95%CI: 0.67-3.38, P = 0.32) may be risk factors for prognosis of osteosarcoma. Conclusion Skp2 is involved in neoadjuvant chemotherapy resistance and in osteosarcomd and is associated with the cell cycle and FOXO pathway.

Key words： Osteosarcoma S phase kinase associated protein 2 Chemotherapy resistance Cell cycle

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	XU Duohui1 DING Lu2 YU Wei1 SONG Zhengnan1 BAI Jingping1

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XU Duohui1 DING Lu2 YU Wei1 SONG Zhengnan1 BAI Jingping1. Correlation of Skp2 high expression with neoadjuvant chemotherapy resistance in patients with osteosarcoma[J]. 中国医药导报, 2020, 17(31): 35-39.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2020/V17/I31/35

[1] Makielski KM，Mills LJ，Sarver AL，et al. Risk Factors for Development of Canine and Human Osteosarcoma：A Comparative Review [J]. Vet Sci，2019，6（2）：48.
[2] El-Naggar AM，Clarkson PW，Negri GL，et al. HACE1 is a potential tumor suppressor in osteosarcoma [J]. Cell Death Dis，2019，10（1）：21.
[3] Ma H，Seebacher NA，Hornicek FJ，et al. Cyclin-dependent kinase 9 （CDK9） is a novel prognostic marker and therapeutic target in osteosarcoma [J]. EBioMedicine，2019，39：182-193.
[4] Moriceau G，Roelofs AJ，Brion R，et al. Synergistic inhibitory effect of apomine and lovastatin on osteosarcoma cell growth [J]. Cancer，2012，118：750-760.
[5] Wang SY，Hu HZ，Qing XC，et al. Recent advances of drug delivery nanocarriers in osteosarcoma treatment [J]. J Cancer，2020，11：69-82.
[6] Xiao X，Wang W，Li Y，et al. HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma [J]. J Exp Clin Cancer Res，2018，37（1）：1-13.
[7] Rodriguez S，Abundis C，Boccalatte F，et al. Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL [J]. Leukemia，2020，34：1241-1252.
[8] Ding L，Wang C，Cui Y，et al. S-phase kinase-associated protein 2 is involved in epithelial-mesenchymal transition in methotrexate-resistant osteosarcoma cells [J]. Int J Oncol，2018，52（6）：1841-1852.
[9] Ding L，Li R，Han X，et al. Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells [J]. Oncol Rep，2017，38（2）：933-940.
[10] Ding L，Li R，Sun R，et al. S-phase kinase-associated protein 2 promotes cell growth and motility in osteosarcoma cells [J]. Cell Cycle，2017，16（16）：1547-1555.
[11] Zhou L，Tang J，Hu F，et al. Effects of different levels of TGF-β expression and tumor cell necrosis rates in osteosarcoma on the chemotherapy resistance of osteosarcoma [J]. J Bone Oncol，2020，23：100299.
[12] Dos Santos Cavalcanti A，Meohas W，Ribeiro GO，et al. Patient-derived osteosarcoma cells are resistant to methotrexate [J]. PLoS One，2017，12：e0184891.
[13] Yu L，Fan Z，Fang S，et al. Cisplatin selects for stem-like cells in osteosarcoma by activating Notch signaling [J]. Oncotarget，2016，7：33055-33068.
[14] Ruan D，He J，Li CF，et al. Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist [J]. Oncogene，2017，36：4299-4310.
[15] Li C，Du L，Ren Y，et al. SKP2 promotes breast cancer tumorigenesis and radiation tolerance through PDCD4 ubiquitination [J]. J Exp Clin Cancer Res，2019，38：76.
[16] Zhang Y，Zvi YS，Batko B，et al. Down-regulation of Skp2 expression inhibits invasion and lung metastasis in osteosarcoma [J]. Sci Rep，2018，8：14294.
[17] Clement E，Inuzuka H，Nihira NT，et al. Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors [J]. Sci Signal，2018，11（521）：eaao3810.
[18] Shi Ni，Yu Hao，Chen Tong，et al. Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway [J]. Onco Targets Ther，2019， 12：7637-7647.
[19] Wu J，Su HK，Yu ZH，et al. Skp2 modulates proliferation，senescence and tumorigenesis of glioma [J]. Cancer Cell Int，2020，20：71.
[20] Jung D，Khurana A，Roy D，et al. Quinacrine upregulates p21/p27 independent of p53 through autophagy-mediated downregulation of p62-Skp2 axis in ovarian cancer [J]. Sci Rep，2018，8（1）：2487.
[21] Liao QD，Zhong D，Chen Q. Protein expression of Skp2 in osteosarcoma and its relation with prognosis [J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban，2008，33（7）：606-611.
[22] Li Y，Nakka M，Kelly AJ，et al. p27 Is a Candidate Prognostic Biomarker and Metastatic Promoter in Osteosarcoma [J]. Cancer Res，2016，76（13）：4002-4011.
[23] Inuzuka H，Gao D，Finley LW，et al. Acetylation-dependent regulation of Skp2 function [J]. Cell，2012，150：179-193.
[24] Schmalhofer O，Brabletz S，Brabletz T. E-cadherin，beta-catenin，and ZEB1 in malignant progression of cancer [J]. Cancer Metastasis Rev，2009，28：151-166.
[25] Wang T，Wang D，Zhang L，et al. The TGFβ-miR-499a-SHKBP1 pathway induces resistance to EGFR inhibitors in osteosarcoma cancer stem cell-like cells [J]. J Exp Clin Cancer Res，2019，38（1）：226.