PMID- 31642260 OWN - NLM STAT- MEDLINE DCOM- 20191025 LR - 20200108 IS - 1872-2059 (Electronic) IS - 1000-8713 (Linking) VI - 37 IP - 8 DP - 2019 Aug 8 TI - [Identification of speckle type BTB/POZ protein mutation regulated key metabolic pathways by cell based proteomics and metabolomics]. PG - 887-896 LID - 10.3724/SP.J.1123.2018.07008 [doi] AB - Speckle type BTB/POZ protein (SPOP) is one of the most frequently mutated protein in prostate cancer. In this study, proteomics and metabolomics were integrated to study the effects of SPOP mutation on metabolism. First, LNCaP control (CON), SPOP wild-type (SPOP_WT), and SPOP mutation (SPOP_Y87N and SPOP_F133L) cells were subjected to a metabolomics study. The metabolomics data of LNCaP CON, SPOP_WT, SPOP_Y87N, and SPOP_F133L cells were evaluated by partial least squares-discriminant analysis (PLS-DA). Four groups could be clearly differentiated with an explanation ability of R(2)X=0.512, R(2)Y=0.616 and predictive ability of Q(2)=0.475. Totally, 36 differential metabolites were defined with variable importance for the projection (VIP) value > 1. Then, the 36 metabolites were subjected to one-way ANOVA analysis. Fumaric acid, malic acid, citric acid, aspartic acid, and asparagine were increased in LNCaP SPOP mutation cells compared to that in LNCaP SPOP_WT cells. Using a proteomics study, 909 differential proteins were found in LNCaP SPOP_Y87N and SPOP_F133L cells. MetaboAnalyst 3.0 was used to enrich metabolic pathways by using differential metabolites. KOBAS 3.0 was used to enrich metabolic pathways by using differential proteins. Both metabolomics and proteomics analysis showed that the tricarboxylic acid (TCA) cycle and aminoacyl-tRNA biosynthesis were significantly changed. To validate these findings, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was performed in Du145 SPOP knock-out cells. The results indicated that the TCA cycle was activated in Du145 SPOP knock-out cells. Collectively, this study found that SPOP mutation significantly promoted TCA cycle in prostate cancer cells. FAU - Yan, Min AU - Yan M AD - Chinese Academy of Sciecne Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. AD - University of Chinese Academy of Sciences, Beijing 100049, China. FAU - Liu, Jing AU - Liu J AD - Chinese Academy of Sciecne Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. FAU - Xia, Tian AU - Xia T AD - Chinese Academy of Sciecne Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. FAU - Xu, Guowang AU - Xu G AD - Chinese Academy of Sciecne Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. FAU - Piao, Hailong AU - Piao H AD - Chinese Academy of Sciecne Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. AD - University of Chinese Academy of Sciences, Beijing 100049, China. LA - chi PT - Journal Article PL - China TA - Se Pu JT - Se pu = Chinese journal of chromatography JID - 9424804 RN - 0 (Nuclear Proteins) RN - 0 (Repressor Proteins) RN - 0 (SPOP protein, human) SB - IM MH - *BTB-POZ Domain MH - Cell Line, Tumor MH - Citric Acid Cycle MH - Humans MH - Male MH - Metabolic Networks and Pathways MH - *Metabolomics MH - Mutation MH - Nuclear Proteins/*genetics MH - Prostatic Neoplasms/*genetics MH - *Proteomics MH - Repressor Proteins/*genetics OTO - NOTNLM OT - metabolomics OT - prostate cancer OT - proteomics OT - speckle type BTB/POZ protein (SPOP) mutation EDAT- 2019/10/24 06:00 MHDA- 2019/10/28 06:00 CRDT- 2019/10/24 06:00 PHST- 2019/10/24 06:00 [entrez] PHST- 2019/10/24 06:00 [pubmed] PHST- 2019/10/28 06:00 [medline] AID - 10.3724/SP.J.1123.2018.07008 [doi] PST - ppublish SO - Se Pu. 2019 Aug 8;37(8):887-896. doi: 10.3724/SP.J.1123.2018.07008.