摘要
Long non-coding RNAs(lncRNAs)play key roles in colorectal carcinogenesis.Here,we aimed to identify the risk SNP-induced lncRNAs and to investigate their roles in colorectal carcinogenesis.First,we identified rs6695584 as the causative SNP in 1 q41 locus.The A>G mutation of rs6695584 created a protein-binding motif of BATF,altered the enhancer activity,and subsequently activated IncSLCCl expression.Further validation in two independent CRC cohorts confirmed the upregulation of IncSLCCl in CRC tissues,and revealed that increased IncSLCCl expression was associated with poor survival in CRC patients.Mechanistically,lncRNA-SLCCl interacted with AHR and transcriptionally activated HK2 expression,the crucial enzyme in glucose metabolism,thereby driving the glycolysis pathway and accelerating CRC tumor growth.The functional assays revealed that IncSLCCl induced glycolysis activation and tumor growth in CRC mediated by HK2.In addition,HK2 was upregulated in colorectal cancer tissues and positively correlated with IncSLCCl expression and patient survival.Taken together,our findings reveal a risk SNP-mediated oncogene lncRNA-SLCCl promotes CRC through activating the glycolysis pathway.
基金
supported in part by grants from the State Key R&D Program(2020YFA0509200)
the National Natural Science Foundation of China(81421001,81530072,81830081,81871901,81874159,81902368,31970718,81770165)
Shanghai Municipal Health Commission,Collaborative Innovation Cluster Project(2019CXJQ02)
"Shu Guang"project supported by Shanghai Municipal Education Commission and Shanghai Education Developm ent Foundation(17SG18)
the Program for Professor of Special Appointm ent(Eastern Scholar No.201268 and 2015 Youth Eastern Scholar No.QD2015003)at Shanghai Institutions of Higher Learning
Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(No.20152512,20161309)
Innovative research team of high-level local universities in Shanghai.
