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Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF‐κB signaling pathway
Cell Biology International ( IF 3.9 ) Pub Date : 2020-09-30 , DOI: 10.1002/cbin.11468
Xinhua Xi 1 , Yongzheng Bao 1 , Yangfan Zhou 2, 3 , Yu Chen 1 , Xueren Zhong 1 , Junjian Liao 1 , Jun Zhou 1 , Sitao Xu 1 , Ziye Cao 1 , Konghe Hu 1 , Yongyu Hu 1 , Xiaolong He 1 , Longze Zhou 1 , Hongsheng Lin 4 , Qiang Wu 1
Affiliation  

Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF‐κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.

中文翻译:

致癌基因TRIM10赋予骨肉瘤细胞对顺铂的抗性并激活NF-κB信号通路

三方基序 (TRIM) 家族蛋白的失调有助于多种生物过程,例如神经变性、发育、炎症、细胞存活、细胞凋亡和致癌作用。然而,TRIM家族蛋白在骨肉瘤化疗耐药中的生物学功能和分子机制尚不清楚。在目前的研究中,我们发现TRIM10的蛋白表达在顺铂耐药的骨肉瘤组织中显着过表达,TRIM10过表达与骨肉瘤患者的生存率呈负相关。此外,TRIM10 的过表达赋予骨肉瘤细胞顺铂抗性;然而,抑制TRIM10使骨肉瘤细胞系在体外对顺铂的细胞毒性敏感。机械上,TRIM10 上调 p65 的核水平,从而激活经典的 NF-κB 信号。
更新日期:2020-09-30
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