Xiaomeng Li1, Heya Na2, Lijie Xu3, Xinsheng Zhang4, Zhen Feng5, Xu Zhou6, Jingyi Cui7, Jingbo Zhang8, Fang Lin9, Shiqing Yang10, Fangxia Yue11, Haithm Mousa12, Yunfei Zuo13. 1. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: lixiaomeng199107@sina.com. 2. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China; Department of Laboratory Medicine, The People's Hospital of Liaoning Province, Shenyang, 110016, China. Electronic address: naheya4987597@163.com. 3. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: xulijiejie@163.com. 4. Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116044, China. Electronic address: zhangxs85@sina.com. 5. Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116044, China. Electronic address: pbzmdr@163.com. 6. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: 549517420@qq.com. 7. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: cuijingyi0906@163.com. 8. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: jingbo1028@163.com. 9. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: 18842682973@163.com. 10. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: 2387702536@qq.com. 11. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: yfx4113320026@163.com. 12. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: 2085810173@qq.com. 13. Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China. Electronic address: zyf04112002@aliyun.com.
Abstract
BACKGROUND: The molecular mechanisms of gastric cancer (GC) development are very complicated. Recent studies revealed that DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein (DC-SIGNR) is involved in colon cancer and GC biological processes. However, the exact roles of DC-SIGN in GC remain unrevealed. METHODS: DC-SIGN overexpression and knockdown experiments were performed by using DC-SIGN shRNA or DC-SIGN plasmid to investigate the biological roles of DC-SIGN in proliferation, cell cycle progression, migration and invasion of GC cells in vitro. Furthermore, the lncRNA profiles of SGC-7901 cells with control shRNA and DC-SIGN shRNA were generated by using microarray analysis. Mechanistically, the relationship between DC-SIGN, RP11-181G12.2 and the JAK2/STAT3 signaling pathway was then investigated using qRT-PCR and western blot assays. Additionally, we analyzed DC-SIGN and RP11-181G12.2 expression levels in GC specimens based on the Cancer Genome Atlas database. RESULTS: In this study, the results showed that DC-SIGN was highly expressed in GC cells and significantly correlated with advanced clinical stage and lymphatic metastasis. Downregulation of DC-SIGN significantly inhibited the proliferation, cell cycle progression, migration and invasion of GC cells in vitro. The reverse results could partly be seen with the upregulation of DC-SIGN. Mechanistically, knockdown of DC-SIGN inactivated the JAK2/STAT3 signaling pathway, and overexpression of DC-SIGN activated the JAK2/STAT3 signaling pathway. In addition, through LncPath microarray analysis, we identified a lncRNA, RP11-181G12.2, that was significantly upregulated after knockdown of DC-SIGN; this was also confirmed by qRT-PCR. Furthermore, RP11-181G12.2 knockdown enhanced DC-SIGN expression in GC cells, further activating the JAK2/STAT3 signaling pathway. In contrast, DC-SIGN overexpression suppressed RP11-181G12.2 expression. CONCLUSIONS: Our study suggests that DC-SIGN might be involved in the progression of GC by regulating the JAK2/STAT3 signaling pathway and affecting lncRNA RP11-181G12.2 expression.
BACKGROUND: The molecular mechanisms of gastric cancer (GC) development are very complicated. Recent studies revealed that DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein (DC-SIGNR) is involved in colon cancer and GC biological processes. However, the exact roles of DC-SIGN in GC remain unrevealed. METHODS:DC-SIGN overexpression and knockdown experiments were performed by using DC-SIGN shRNA or DC-SIGN plasmid to investigate the biological roles of DC-SIGN in proliferation, cell cycle progression, migration and invasion of GC cells in vitro. Furthermore, the lncRNA profiles of SGC-7901 cells with control shRNA and DC-SIGN shRNA were generated by using microarray analysis. Mechanistically, the relationship between DC-SIGN, RP11-181G12.2 and the JAK2/STAT3 signaling pathway was then investigated using qRT-PCR and western blot assays. Additionally, we analyzed DC-SIGN and RP11-181G12.2 expression levels in GC specimens based on the Cancer Genome Atlas database. RESULTS: In this study, the results showed that DC-SIGN was highly expressed in GC cells and significantly correlated with advanced clinical stage and lymphatic metastasis. Downregulation of DC-SIGN significantly inhibited the proliferation, cell cycle progression, migration and invasion of GC cells in vitro. The reverse results could partly be seen with the upregulation of DC-SIGN. Mechanistically, knockdown of DC-SIGN inactivated the JAK2/STAT3 signaling pathway, and overexpression of DC-SIGN activated the JAK2/STAT3 signaling pathway. In addition, through LncPath microarray analysis, we identified a lncRNA, RP11-181G12.2, that was significantly upregulated after knockdown of DC-SIGN; this was also confirmed by qRT-PCR. Furthermore, RP11-181G12.2 knockdown enhanced DC-SIGN expression in GC cells, further activating the JAK2/STAT3 signaling pathway. In contrast, DC-SIGN overexpression suppressed RP11-181G12.2 expression. CONCLUSIONS: Our study suggests that DC-SIGN might be involved in the progression of GC by regulating the JAK2/STAT3 signaling pathway and affecting lncRNA RP11-181G12.2 expression.