Cheng Shimeng, Mao Qiqi, Dong Yabing, Ren Jie, Su Lina, Liu Jianlan, Liu Qingmei, Zhou Jing, Ye Xiaolu, Zheng Shudan, Zhu Ningwen
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Physiology, Hainan Medical College, Haikou, China.
PLoS One. 2017 Aug 10;12(8):e0182696. doi: 10.1371/journal.pone.0182696. eCollection 2017.
GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer.
据报道，GNB2L1及其O-连接的N-乙酰葡糖胺化在胃癌转移中发挥作用。然而，GNB2L1在胃癌化疗耐药中的作用尚未确定。在本研究中，我们发现GNB2L1在胃癌化疗耐药患者中表达下调，并且在不同的化疗耐药胃癌细胞系中观察到GNB2L1蛋白水平而非mRNA水平降低，并进一步证明在细胞系和患者中，GNB2L1的这种下调是由OGT催化的其O-连接的N-乙酰葡糖胺化升高所致。接下来，我们研究了GNB2L1及其O-连接的N-乙酰葡糖胺化在化疗耐药期间对胃癌转移的作用，并确定Ser124是GNB2L1上调节其转移功能的主要O-连接的N-乙酰葡糖胺化位点。此外，我们的数据表明，在化疗耐药过程中，GNB2L1通过调节EMT相关蛋白的翻译来调节EMT。总之，本研究表明，GNB2L1及其O-连接的N-乙酰葡糖胺化在胃癌化疗耐药中通过调节EMT相关蛋白的翻译来调节转移。
