VAX2-LINC01189-hnRNPF 信号轴调节胃癌细胞侵袭和迁移。
The VAX2-LINC01189-hnRNPF signaling axis regulates cell invasion and migration in gastric cancer.
发表日期：2023 Oct 21
作者：
Linjie Hong, Ping Yang, Luyu Zhang, Xuehua Liu, Xiangyang Wei, Wushuang Xiao, Zhen Yu, Jieming Zhang, Ying Peng, Xiaosheng Wu, Weimei Tang, Fachao Zhi, Guoxin Li, Aimin Li, Jianjiao Lin, Side Liu, Hui Zhang, Li Xiang, Jide Wang
来源：
Cell Death & Disease
摘要：
转录因子 (TF) 和长链非编码 RNA (lncRNA) 会导致胃癌 (GC)。然而，TF和lncRNA在GC侵袭和转移中的作用仍然很大程度上未知。在这里，我们观察到转录因子 VAX2 在 GC 细胞和组织中显着上调，并充当癌基因。此外，VAX2的高表达与GC中肿瘤的进展相关。从功能上来说，VAX2的强制表达可促进GC细胞的增殖和转移。从机制上讲，VAX2 与 LINC01189 启动子特异性相互作用并抑制 LINC01189 转录。此外，LINC01189 在 GC 中表现出显着的下调，并起到抑制基因的作用。从功能上讲，它抑制 GC 细胞的迁移和侵袭能力。在GC转移的背景下，VAX2通过反式抑制LINC01189的表达发挥调节作用。此外，LINC01189 与 hnRNPF 结合，通过泛素化增强 hnRNPF 降解。 LINC01189 和 hnRNPF 之间的合作调节 GC 细胞的侵袭和迁移。此外，与正常胃组织相比，VAX2和hnRNPF在GC组织中均高表达，而LINC01189在GC组织中低水平表达。我们的研究表明，VAX2 表达促进转移，而 LINC01189 表达抑制转移，并且 VAX2-LINC01189-hnRNPF 轴在 GC 发展中发挥着重要作用。© 2023。细胞死亡分化协会 (ADMC)。
Transcription factors (TFs) and long noncoding RNAs (lncRNAs) contribute to gastric cancer (GC). However, the roles of TFs and lncRNAs in the invasion and metastasis of GC remain largely unknown. Here, we observed that the transcription factor VAX2 is significantly upregulated in GC cells and tissues and acts as an oncogene. Moreover, high VAX2 expression is associated with the advancement of tumors in GC. In terms of functionality, the enforced expression of VAX2 promotes the proliferation and metastasis of GC cells. Mechanistically, VAX2 specifically interacts with the LINC01189 promoter and represses LINC01189 transcription. Furthermore, LINC01189 exhibits significant downregulation in GC and functions as a suppressor gene. Functionally, it inhibits migratory and invasive abilities in GC cells. In the context of GC metastasis, VAX2 plays a role in modulating it by trans-repressing the expression of LINC01189. Additionally, LINC01189 binds to hnRNPF to enhance hnRNPF degradation through ubiquitination. The cooperation between LINC01189 and hnRNPF regulates GC cell invasion and migration. In addition, both VAX2 and hnRNPF are highly expressed, while LINC01189 is expressed in at low levels in GC tissues compared to normal gastric tissues. Our study suggests that VAX2 expression facilitates, while LINC01189 expression suppresses, metastasis and that the VAX2-LINC01189-hnRNPF axis plays a contributory role in GC development.© 2023. Cell Death Differentiation Association (ADMC).