Quantitative global proteome and lysine succinylome analyses provide insights into metabolic regulation and lymph node metastasis in gastric cancer.
With the rapid development of high-throughput quantitative proteomic and transcriptomic approaches, the molecular mechanisms of cancers have been comprehensively explored. However, cancer is a multi-dimensional disease with sophisticated regulations, and few studies focus on the crosstalk among multiomics. In order to explore the molecular mechanisms of gastric cancer (GC), particularly in the process of lymph node metastasis (LNM), we investigated dynamic profiling changes as well as crosstalk between long non-coding RNAs (lncRNAs), the proteome, and the lysine succinylome. Our study reports the first qualitative and quantitative profile of lysine succinylation in GC. We identified a novel mechanism through which the TCA cycle and pentose phosphate pathway might be regulated through lysine succinylation in their core enzymes. We then examined the potential of using lysine succinylation as a biomarker for GC and successfully developed a succinylation-dependent antibody for the K569 site in Caldesmon as putative biomarker. Finally, we investigated the relationship between the lysine succinylome and lncRNAs, identifying potential crosstalks between two lncRNAs and one succinylation site. These results expand our understanding of the mechanisms of tumorigenesis and provide new information for the diagnosis and prognosis of GC.
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Yongxi
Y
Song
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Jun
J
Wang
Jingjie PTM BioLab (Hangzhou) Co. Ltd, No.452, 6th Street, Hangzhou Eco.&Tech. Developmental Area, Hangzhou 310018, China.
Zhongyi
Z
Cheng
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Peng
P
Gao
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Jingxu
J
Sun
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Xiaowan
X
Chen
Jingjie PTM BioLab (Hangzhou) Co. Ltd, No.452, 6th Street, Hangzhou Eco.&Tech. Developmental Area, Hangzhou 310018, China.
Chen
C
Chen
Jingjie PTM BioLab (Hangzhou) Co. Ltd, No.452, 6th Street, Hangzhou Eco.&Tech. Developmental Area, Hangzhou 310018, China.
Yunlong
Y
Wang
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Zhenning
Z
Wang
D000368:Aged; D000941:Antigens; D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins / Q000276:immunology; D002952:Citric Acid Cycle; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008239:Lysine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020543:Proteome; D062085:RNA, Long Noncoding; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019802:Succinic Acid / Q000378:metabolism*
D000941:Antigens; D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D020543:Proteome; D062085:RNA, Long Noncoding; D019802:Succinic Acid; D008239:Lysine