Background

Emerging evidence indicates a regulatory role of long non-coding RNAs (lncRNAs) in the development of gastric cancer (GC), but the mechanisms underlying their function have remained largely unknown. Recent microarray-based expression profiling has led to the identification of a novel differentially expressed lncRNA, LINC00858, in GC. Subsequently, LINC00858 was found to be highly expressed in GC tissues and cells. This study was designed to clarify the functional role of LINC00858 in GC, including its effect on methylation of the WNK2 gene promoter and its downstream MAPK signaling pathway.

Methods

After exogenous over-expression and knockdown of LINC00858 and the addition of a MAPK pathway inhibitor in GC cells, we explored the effects of LINC00858 and the MAPK signaling pathway on GC cell behavior using various in vitro and in vivo assays.

Results

LINC00858 was found to negatively regulate WNK2 expression by enhancing its promoter methylation and to activate the MAPK signaling pathway. Moreover, we found that knockdown of LINC00858 or inhibition of the MAPK signaling pathway resulted in decreased GC cell growth, migration and invasion, as well as decreased cell cycle progression, along with increased apoptosis and decreased tumorigenicity.

Conclusions

Together, these findings indicate that silencing of LINC00858 increases WNK2 expression and inhibits the MAPK signaling pathway, thereby inhibiting GC growth and development. Our data highlight LINC00858 as a potential target in GC therapy.

中文翻译：

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LINC00858抑制基因通过减少WNK2启动子甲基化抑制胃癌细胞生长并诱导凋亡。

背景

越来越多的证据表明，长链非编码RNA（lncRNA）在胃癌（GC）的发生中起调节作用，但其功能基础的机制仍不清楚。最近基于微阵列的表达谱分析已导致在GC中鉴定出新型差异表达的lncRNA LINC00858。随后，发现LINC00858在GC组织和细胞中高表达。这项研究旨在阐明LINC00858在GC中的功能，包括其对WNK2基因启动子甲基化及其下游MAPK信号通路的影响。

方法

在GC细胞中外源过量表达和敲低LINC00858并添加MAPK途径抑制剂后，我们使用各种体外和体内试验探索了LINC00858和MAPK信号传导途径对GC细胞行为的影响。

结果

发现LINC00858通过增强其启动子甲基化来负调控WNK2表达并激活MAPK信号通路。此外，我们发现敲低LINC00858或抑制MAPK信号通路会导致GC细胞生长，迁移和侵袭减少，以及细胞周期进程减少，以及凋亡增加和致瘤性降低。

结论

在一起，这些发现表明，LINC00858的沉默增加WNK2表达并抑制MAPK信号传导途径，从而抑制GC的生长和发育。我们的数据强调了LINC00858作为GC治疗中的潜在靶标。