Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang 110001, China.
Jingjie PTM BioLab (Hangzhou) Co. Ltd, No.452, 6th Street, Hangzhou Eco.&Tech. Developmental Area, Hangzhou 310018, China.
Sci Rep. 2017 Feb 6;7:42053. doi: 10.1038/srep42053.
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.
随着高通量定量蛋白质组学和转录组学方法的快速发展，癌症的分子机制已经得到了全面的探索。然而，癌症是一种具有复杂调控机制的多维疾病，很少有研究关注多组学之间的串扰。为了探索胃癌（GC）的分子机制，特别是在淋巴结转移（LNM）过程中，我们研究了长非编码 RNA（lncRNA）、蛋白质组和赖氨酸琥珀酰化组之间的动态谱变化及其串扰。我们的研究报告了 GC 中赖氨酸琥珀酰化的第一个定性和定量图谱。我们发现了一种新的机制，即 TCA 循环和磷酸戊糖途径可能通过其核心酶中的赖氨酸琥珀酰化来调节。然后，我们研究了将赖氨酸琥珀酰化作为 GC 生物标志物的潜力，并成功开发了用于 Caldesmon 中 K569 位点的琥珀酰化依赖性抗体作为潜在的生物标志物。最后，我们研究了赖氨酸琥珀酰化组与 lncRNA 之间的关系，确定了两个 lncRNA 和一个琥珀酰化位点之间的潜在串扰。这些结果扩展了我们对肿瘤发生机制的理解，并为 GC 的诊断和预后提供了新的信息。
