PMID- 29502225 OWN - NLM STAT- MEDLINE DCOM- 20191219 LR - 20210109 IS - 1532-2807 (Electronic) IS - 1219-4956 (Linking) VI - 25 IP - 3 DP - 2019 Jul TI - Quantitative Proteomics Identify the Possible Tumor Suppressive Role of Protease-Activated Receptor-4 in Esophageal Squamous Cell Carcinoma Cells. PG - 937-943 LID - 10.1007/s12253-018-0395-7 [doi] AB - Exposure to carcinogens of tobacco smoke may result in methylation of protease-activated receptors-4 (PAR4) gene and further induces the loss of PAR4 expression, which is considered to be involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC). Here we employed a TMT-based quantitative proteomic approach to identify PAR4-regulated changes of proteomic profiles in ESCC cells and to identify potentially therapeutic value. A total of 33 proteins were found significantly changed with 15 up-regulated and 18 down-regulated in PAR4-activating peptide (PAR4-AP) treated ESCC cells compared with controls. Bioinformatics analysis showed that key higher expressed proteins included those associated with apoptosis and tumor suppressor (e.g. CASP9), and lower expressed proteins included those associated with anti-apoptosis, autophagy and promoting cell proliferation (e.g. CHMP1B, PURA, PARG and HIST1H2AH). Western blot verified changes in five representative proteins including CASP9, CHMP1B, PURA, PARG and HIST1H2AH. Immunohistochemistry analysis showed that CHMP1B, PURA, PARG and HIST1H2AH expression in ESCC tissues were significantly higher than those in adjacent nontumorous tissues. Our findings will be helpful in further investigations into the functions and molecular mechanisms of PAR4 in ESCC. FAU - Wang, Ming AU - Wang M AD - Department of Human Anatomy, Taishan Medical University, 2 Ying Sheng Dong Lu, Tai'an, 271000, China. FAU - An, Shuhong AU - An S AD - Department of Human Anatomy, Taishan Medical University, 2 Ying Sheng Dong Lu, Tai'an, 271000, China. FAU - Wang, Diyi AU - Wang D AD - Department of Pathology, Affiliated Hospital of Taishan Medical University, Tai'an, 271000, China. FAU - Ji, Haizhen AU - Ji H AD - Department of Physiology, Taishan Medical University, Tai'an, China. FAU - Geng, Min AU - Geng M AD - Department of Human Anatomy, Taishan Medical University, 2 Ying Sheng Dong Lu, Tai'an, 271000, China. FAU - Guo, Xingjing AU - Guo X AD - Department of Physiology, Taishan Medical University, Tai'an, China. FAU - Wang, Zhaojin AU - Wang Z AD - Department of Human Anatomy, Taishan Medical University, 2 Ying Sheng Dong Lu, Tai'an, 271000, China. zjwang@tsmc.edu.cn. LA - eng GR - 81371234/National Natural Science Foundation of China/ GR - 2016ZRB14346/Natural Science Foundation of Shandong Province, China/ PT - Journal Article DEP - 20180304 PL - Switzerland TA - Pathol Oncol Res JT - Pathology oncology research : POR JID - 9706087 RN - 0 (Receptors, Thrombin) RN - JWE1M73YZN (protease-activated receptor 4) SB - IM MH - Apoptosis/genetics MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Down-Regulation/genetics MH - Esophageal Neoplasms/*genetics MH - Esophageal Squamous Cell Carcinoma/*genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - Immunohistochemistry/methods MH - Promoter Regions, Genetic/genetics MH - Proteomics/methods MH - Receptors, Thrombin/*genetics MH - Up-Regulation/genetics OTO - NOTNLM OT - Apoptosis OT - Esophageal squamous cell carcinoma OT - Protease-activated receptors-4 OT - Proteomic OT - Tumor suppressor EDAT- 2018/03/05 06:00 MHDA- 2019/12/20 06:00 CRDT- 2018/03/05 06:00 PHST- 2017/11/28 00:00 [received] PHST- 2018/02/21 00:00 [accepted] PHST- 2018/03/05 06:00 [pubmed] PHST- 2019/12/20 06:00 [medline] PHST- 2018/03/05 06:00 [entrez] AID - 10.1007/s12253-018-0395-7 [pii] AID - 10.1007/s12253-018-0395-7 [doi] PST - ppublish SO - Pathol Oncol Res. 2019 Jul;25(3):937-943. doi: 10.1007/s12253-018-0395-7. Epub 2018 Mar 4.