Xu Xiaohong, Liu Jing, Shen Chaoyan, Ding Linlin, Zhong Fei, Ouyang Yu, Wang Yuchan, He Song
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu Province, China.
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China.
Eur J Haematol. 2017 Jan;98(1):4-12. doi: 10.1111/ejh.12729. Epub 2016 Nov 2.
Cell adhesion-mediated drug resistance (CAM-DR) is one of the mechanisms underlying the drug resistance in multiple myeloma (MM). Ubiquitin-specific protease 14 (USP14) is downregulated in the apoptotic model and upregulated in the adhesive model of MM. This study was undertaken to determine the role of USP14 in CAM-DR of MM cells.
We examined the expression of USP14 in the apoptotic model of MM. The mechanism of USP14 in the process of apoptosis was further explored by flow cytometry assay and co-immunoprecipitation. We then performed the cell co-culture and adhesion assay and cell viability assay to investigate the effect of USP14 on adhesive rate and drug resistance in MM.
We discovered that USP14 played a negative role in cell apoptosis, which is correlated with Bcl-xl. Moreover, overexpression of USP14 in MM cell adhesion model could enhance the ability of cell adhesion by regulating Wnt-signaling pathways, thereby promoting the CAM-DR in MM.
USP14 participates in CAM-DR of MM through acting as a bridge between Bcl-xl apoptotic pathway and Wnt-signaling pathways and may be represented as a good candidate for pursuing clinical trials in MM.
细胞黏附介导的耐药性（CAM-DR）是多发性骨髓瘤（MM）耐药的机制之一。泛素特异性蛋白酶14（USP14）在MM的凋亡模型中表达下调，而在黏附模型中表达上调。本研究旨在确定USP14在MM细胞CAM-DR中的作用。
我们检测了MM凋亡模型中USP14的表达。通过流式细胞术检测和免疫共沉淀进一步探究USP14在凋亡过程中的机制。然后进行细胞共培养、黏附实验和细胞活力实验，以研究USP14对MM细胞黏附率和耐药性的影响。
我们发现USP14在细胞凋亡中起负性作用，这与Bcl-xl相关。此外，在MM细胞黏附模型中过表达USP14可通过调节Wnt信号通路增强细胞黏附能力，从而促进MM中的CAM-DR。
USP14通过作为Bcl-xl凋亡通路和Wnt信号通路之间的桥梁参与MM的CAM-DR，可能是MM临床试验的良好候选靶点。
