Citation: WANG Zhi-Chao, LIU Jing, PIAO Hai-Long. Capillary Electrophoresis-Mass Spectrometry Based Metabolomics Analysis of Metabolic Reprogramming Induced by Phosphatase and Tensin Homolog[J]. Chinese Journal of Analytical Chemistry, ;2019, 47(1): 59-66. doi: 10.19756/j.issn.0253-3820.181600 shu

Capillary Electrophoresis-Mass Spectrometry Based Metabolomics Analysis of Metabolic Reprogramming Induced by Phosphatase and Tensin Homolog

1.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;
2.
University of Chinese Academy of Sciences, Beijing 100049, China

Received Date: 18 September 2018
Revised Date: 2 November 2018

Fund Project: The work was supported by the National Natural Science Foundation of China (Nos.81672440, 81702771) and the Innovation Program of Science and Research from the DICP, CAS (No. DICP TMSR201601).

Prostate cancer is the most frequently occurred cancer in males. Phosphatase and tensin homolog (PTEN) deficiency often occurs in prostate cancer and induces metabolic reprogramming. Metabolic vulnerabilities induced by PTEN deficiency may provide therapeutic targets for cancer therapy. Here, capillary electrophoresis-mass spectrometry (CE-MS) based metabolomics analysis was used for analyzing metabolic changes induced by PTEN deficiency in prostate cancer cell DU145 and normal prostate cell RWPE1. 200 and 214 metabolites were detected, and 28 and 37 differential metabolites were authenticated in PTEN knock-downed DU145 and RWPE1 cells compared to their controls, respectively. Threonic acid levels increased, while isobutyrylcarnitine, adenosine diphosphate, N-glycolylneuraminic acid, Asp, hypotaurine levels decreased after PTEN silencing in both cell lines. The specific metabolites changes in DU145 after PTEN silencing were L-2-HG, glycerophosphocholine, thiamine, the ratio of GSH to GSSG, and all of them were increased. These metabolites can promote tumor proliferation, metastasis, and resistance to chemotherapy. Creatinine, carnosine and N-acetylneuraminic acid, which had been reported to be biomarkers of cancer diagnosis and prognosis, were regulated by PTEN deficiency. Metabolites changes induced by PTEN deficiency only or combined effect of PTEN deficiency and other cancer-related genes were identified.
- Capillary electrophoresis-mass spectrometry,
- Cell metabolomics,
- Phosphatase and tensin homolog,
- Metabolic reprogramming,
- Prostate cancer
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