Yang Li, Lin Xiao-Lu, Liang Wei, Fu Seng-Wang, Lin Wen-Feng, Tian Xiao-Qing, Gao Yun-Jie, Chen Hao-Yan, Dai Jun, Ge Zhi-Zheng
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200001, China.
Department of Digestive Endoscopy, Provincial Clinic Medical College, Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, China.
Oncotarget. 2017 Jul 18;8(29):47943-47956. doi: 10.18632/oncotarget.18203.
Previous studies have found that G-protein-coupled receptor 116 (GPR116) is a regulator of breast cancer metastasis. However, the role of GPR116 in colorectal carcinoma (CRC) carcinogenesis and progression is unknown. In this study, We found GPR116 expression was significantly up-regulated in CRC specimens compared with corresponding non-cancerous tissues. Increased GPR116 expression in CRC was correlated with histological differentiation and distant metastasis. In addition, high expression of GPR116 was significantly associated with poor overall survival of CRC patients, which was also confirmed by GSE14333, GSE17536 and GSE33113 datasets from the Gene Expression Omnibus (GEO). Furthermore, we demonstrated that the ability of proliferation and invasion of CRC cell lines HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may drive EMT in CRC cells through AKT/EKR signaling pathway, resulting in metastasis. Thus, GPR116 may be a novel reliable prognostic indicator and a risk factor in CRC progression.
先前的研究发现,G蛋白偶联受体116(GPR116)是乳腺癌转移的一个调节因子。然而,GPR116在结直肠癌(CRC)发生和进展中的作用尚不清楚。在本研究中,我们发现与相应的非癌组织相比,CRC标本中GPR116的表达显著上调。CRC中GPR116表达的增加与组织学分化和远处转移相关。此外,GPR116的高表达与CRC患者较差的总生存期显著相关,这也得到了来自基因表达综合数据库(GEO)的GSE14333、GSE17536和GSE33113数据集的证实。此外,我们证明,用siRNA-GPR116转染后,CRC细胞系HCT116和LOVO的增殖和侵袭能力明显降低。同时,GPR116可能通过AKT/EKR信号通路驱动CRC细胞中的上皮-间质转化(EMT),从而导致转移。因此,GPR116可能是CRC进展中一种新型可靠的预后指标和危险因素。