DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis.
DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis.
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DC-SIGNR通过影响lncRNA HNRNPKP2上调胃癌肝转移中CXCR4的表达
DOI：
10.1186/s12943-017-0639-2
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发表时间：
2017-04-13
期刊：
影响因子：
37.3
通讯作者：
Zuo Y
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhang Q;Zhang M;Yuan M;Wang Z;Zhang J;Zhou X;Zhang Y;Lin F;Na H;Ren S;Zuo Y
研究背景选择素在肿瘤的发生、发展和转移过程中起着重要作用。然而，DC-SIGNR作为选择素家族成员参与胃癌肝转移尚不清楚。慢病毒介导DC-SIGNR在BGC 823和SGC 7901细胞系中的表达。通过MTT法、创伤法、transwell法等体外生物学实验和IVIS法证实胃癌肝转移的动物实验研究DC-SIGNR的生物学效应。利用微阵列技术和生物信息学分析方法对该机制进行了深入研究。结果胃癌患者血清DC-SIGNR水平明显高于健康对照组，差异有统计学意义（P < 0. 05）。此外，DC-SIGNR水平与胃癌患者的晚期病理分期相关。DC-SIGNR基因敲低可抑制胃癌细胞的增殖、迁移和侵袭能力，并抑制体内肝转移。而DC-SIGNR过表达促进细胞增殖、迁移和侵袭。在机制上，HNRNPKP 2作为lncRNA在DC-SIGNR敲低后上调。重要的是，STAT 5A在敲低DC-SIGNR后促进HNRNPKP 2表达。结论DC-SIGNR可促进HNRNPKP 2介导的胃癌肝转移，HNRNPKP 2的表达受STAT 5A的调控。HNRNPKP 2可降低下游靶基因CXCR 4的表达。这些发现为胃癌肝转移提供了潜在的治疗候选者。
BackgroundProfiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis. However, DC-SIGNR as a family member of selectin participates in gastric cancer liver metastasis remains unknown.MethodsThe serum level of DC-SIGNR was evaluated in gastric cancer patients by ELISA. Manipulation DC-SIGNR expression in BGC823 and SGC7901 cell lines was mediated by lentivirus. Investigation the biological effects of DC-SIGNR were verified by MTT, wounding and transwell in vitro and experiments on animals to confirm gastric cancer liver metastasis by IVIS. Insights of the mechanism were employed microarray and bioinformatic analysis. Further to confirm the results were conducted by qRT-PCR, western blot and by flow cytometry.ResultsDC-SIGNR serum level was significantly increased in gastric cancer patients compared with healthy group. Additionally, DC-SIGNR level was associated with an advanced pathological stage in gastric cancer patients. DC-SIGNR knockdown inhibited the proliferation, migration and invasion of gastric cancer cells in vitro and suppressed the liver metastasis in vivo. While, DC-SIGNR overexpression promoted cell proliferation, migration and invasion. In mechanism, HNRNPKP2 as a lncRNA was upregulated after DC-SIGNR knockdown. Importantly, STAT5A promoted HNRNPKP2 expression after knockdown DC-SIGNR. Furthermore after HNRNPKP2 depletion, the downstream target gene CXCR4 was downregulated.ConclusionsDC-SIGNR promoted gastric cancer liver metastasis mediated with HNRNPKP2 which expression was regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target gene CXCR4. These findings indicated potential therapeutic candidates for gastric cancer liver metastasis.