DC-SIGN 通过调节 JAK2/STAT3 信号通路并影响 LncRNA RP11-181G12.2 的表达来介导胃癌的进展。
DC-SIGN mediates gastric cancer progression by regulating the JAK2/STAT3 signaling pathway and affecting LncRNA RP11-181G12.2 expression.
机构信息
Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China.
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.
出版信息
Biomed Pharmacother. 2020 Jan;121:109644. doi: 10.1016/j.biopha.2019.109644. Epub 2019 Nov 19.
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.
背景
胃癌（GC）的发展的分子机制非常复杂。最近的研究表明，树突状细胞特异性细胞间黏附分子 3 抓取非整联蛋白（DC-SIGN）相关蛋白（DC-SIGNR）参与结肠癌和 GC 的生物学过程。然而，DC-SIGN 在 GC 中的确切作用仍未被揭示。
方法
通过使用 DC-SIGN shRNA 或 DC-SIGN 质粒进行 DC-SIGN 过表达和敲低实验，研究 DC-SIGN 在体外 GC 细胞增殖、细胞周期进程、迁移和侵袭中的生物学作用。此外，使用微阵列分析生成具有对照 shRNA 和 DC-SIGN shRNA 的 SGC-7901 细胞的长链非编码 RNA 图谱。通过 qRT-PCR 和 Western blot 检测，进一步研究了 DC-SIGN、RP11-181G12.2 与 JAK2/STAT3 信号通路之间的关系。此外，我们根据癌症基因组图谱数据库分析了 GC 标本中 DC-SIGN 和 RP11-181G12.2 的表达水平。
结果
在这项研究中，结果表明 DC-SIGN 在 GC 细胞中高表达，并且与晚期临床分期和淋巴转移显著相关。DC-SIGN 的下调显著抑制了 GC 细胞在体外的增殖、细胞周期进程、迁移和侵袭。用 DC-SIGN 的上调可观察到相反的结果。机制上，DC-SIGN 的敲低使 JAK2/STAT3 信号通路失活，而 DC-SIGN 的过表达使 JAK2/STAT3 信号通路激活。此外，通过 LncPath 微阵列分析，我们鉴定了一个在 DC-SIGN 敲低后显著上调的长链非编码 RNA，RP11-181G12.2，这也通过 qRT-PCR 得到了证实。此外，RP11-181G12.2 的敲低增强了 GC 细胞中 DC-SIGN 的表达，进一步激活了 JAK2/STAT3 信号通路。相反，DC-SIGN 的过表达抑制了 RP11-181G12.2 的表达。
结论
我们的研究表明，DC-SIGN 可能通过调节 JAK2/STAT3 信号通路和影响 lncRNA RP11-181G12.2 的表达，参与 GC 的进展。
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