Background

Long non-coding RNAs (LncRNAs) are closely related to the occurrence of cancer, but its mechanism in gastric cancer (GC) is still largely unclear.

Aims

This study aimed to reveal the underlying mechanism of LncRNA ANCR in GC.

Methods

The expression of LncRNA ANCR was detected by qRT-PCR. ELISA was used to identify THP-1 cells into macrophage M1 type polarization. After macrophages overexpressing LncRNA ANCR were co-cultured with GC cell HGC-27, the invasion and metastasis of GC were analyzed by Transwell assay. The targeted regulation of FoxO1 by LncRNA ANCR was analyzed by RNA pull-down, RNA immunoprecipitation (RIP), and Western blot. The BALB/c nude mouse model of GC was established to analyze the effect of LncRNA ANCR on tumor growth.

Results

LncRNA ANCR was highly expressed in GC. The overexpression of LncRNA ANCR in macrophages reduced the concentrations of M1 macrophage polarized marker molecules IL-1β and IL-6 in the supernatant of cells, and inhibited the polarization of macrophages to M1, while the knockdown of LncRNA ANCR produced the opposite effect. The co-culture of macrophages overexpressing LncRNA ANCR with GC cells promoted the invasion and migration of cells. LncRNA ANCR targeted FoxO1 and inhibited the expression of FoxO1 in THP-1 cells by promoting FoxO1 ubiquitination degradation. In addition, the overexpression of LncRNA ANCR promoted tumor growth in a BALB/c nude mouse model of GC, while the knockdown of LncRNA ANCR produced the opposite effect.

Conclusions

Based on these results, the overexpression of LncRNA ANCR promoted the invasion and metastasis of GC cells via down-regulating FoxO1 to inhibit macrophage polarization to M1.

中文翻译：

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LncRNA ANCR通过调节FoxO1表达以抑制巨噬细胞M1极化来促进胃癌的侵袭和迁移。

背景

长的非编码RNA（LncRNA）与癌症的发生密切相关，但其在胃癌（GC）中的机制仍不清楚。

目的

这项研究旨在揭示GC中LncRNA ANCR的潜在机制。

方法

通过qRT-PCR检测LncRNA ANCR的表达。ELISA用于鉴定THP-1细胞进入巨噬细胞M1型极化。将过表达LncRNA ANCR的巨噬细胞与GC细胞HGC-27共培养后，通过Transwell法分析GC的侵袭和转移。LncRNA ANCR对FoxO1的靶向调控通过RNA下拉，RNA免疫沉淀（RIP）和Western印迹进行了分析。建立了GC的BALB / c裸鼠模型，以分析LncRNA ANCR对肿瘤生长的影响。

结果

LncRNA ANCR在GC中高表达。LncRNA ANCR在巨噬细胞中的过表达降低了细胞上清液中M1巨噬细胞极化标记分子IL-1β和IL-6的浓度，并抑制了巨噬细胞向M1的极化，而敲低LncRNA ANCR则产生了相反的作用。过量表达LncRNA ANCR的巨噬细胞与GC细胞的共培养促进了细胞的侵袭和迁移。LncRNA ANCR靶向FoxO1，并通过促进FoxO1泛素化降解而抑制THP-1细胞中FoxO1的表达。此外，LncRNA ANCR的过表达促进了GC的BALB / c裸鼠模型中肿瘤的生长，而LncRNA ANCR的敲除产生了相反的作用。

结论

基于这些结果，LncRNA ANCR的过表达通过下调FoxO1抑​​制巨噬细胞向M1的极化而促进了GC细胞的侵袭和转移。