PMID- 26710889 OWN - NLM STAT- MEDLINE DCOM- 20170206 LR - 20190402 IS - 1600-0609 (Electronic) IS - 0902-4441 (Linking) VI - 98 IP - 1 DP - 2017 Jan TI - The role of ubiquitin-specific protease 14 (USP14) in cell adhesion-mediated drug resistance (CAM-DR) of multiple myeloma cells. PG - 4-12 LID - 10.1111/ejh.12729 [doi] AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CI - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Xu, Xiaohong AU - Xu X AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu Province, China. FAU - Liu, Jing AU - Liu J AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China. FAU - Shen, Chaoyan AU - Shen C AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China. FAU - Ding, Linlin AU - Ding L AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China. FAU - Zhong, Fei AU - Zhong F AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China. FAU - Ouyang, Yu AU - Ouyang Y AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China. FAU - Wang, Yuchan AU - Wang Y AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, China. FAU - He, Song AU - He S AD - Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu Province, China. LA - eng PT - Journal Article DEP - 20161102 PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (Antineoplastic Agents) RN - 0 (USP14 protein, human) RN - 0 (bcl-X Protein) RN - BZ114NVM5P (Mitoxantrone) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) SB - IM MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects/genetics MH - Cell Adhesion/genetics MH - Cell Line, Tumor MH - Cell Survival/drug effects/genetics MH - Drug Resistance, Neoplasm/*genetics MH - Gene Expression MH - Humans MH - Mitoxantrone/pharmacology MH - Multiple Myeloma/*genetics/metabolism MH - Ubiquitin Thiolesterase/*genetics/metabolism MH - bcl-X Protein/metabolism OTO - NOTNLM OT - Multiple myeloma OT - Ubiquitin-specific protease 14 OT - apoptosis OT - cell adhesion-mediated drug resistance EDAT- 2016/11/03 06:00 MHDA- 2017/02/07 06:00 CRDT- 2015/12/30 06:00 PHST- 2015/12/21 00:00 [accepted] PHST- 2016/11/03 06:00 [pubmed] PHST- 2017/02/07 06:00 [medline] PHST- 2015/12/30 06:00 [entrez] AID - 10.1111/ejh.12729 [doi] PST - ppublish SO - Eur J Haematol. 2017 Jan;98(1):4-12. doi: 10.1111/ejh.12729. Epub 2016 Nov 2.