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LncRNA ANCR Promotes Invasion and Migration of Gastric Cancer by Regulating FoxO1 Expression to Inhibit Macrophage M1 Polarization

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Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

    Chunying Xie & Yanyan Guo

  2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Min-De Road, Nanchang, 330006, Jiangxi Province, China

    Siyuan Lou

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  1. Chunying Xie
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Correspondence to Siyuan Lou.

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Supplementary Fig. 1

Knockdown of LncRNA ANCR promoted macrophage M1 polarization and repressed the growth of GC in xenograft. si-ANCR was transfected into THP-1 cells, and THP-1 cells were induced to differentiate into M1 macrophages. (A) The concentrations of IL-1β and IL-6 in macrophage supernatants were measured by ELISA. After the knockdown of LncRNA ANCR in xenograft, (B) Tumor volume was measured every 7 d, and nude mice were killed on the 28th day. (*P < 0.05, compared with si-control group or Lenti-si-NC group). (TIFF 1461 kb)

Supplementary Fig. 2

Correlation between FoxO1 and IL-1β and IL-6 concentrations. After transfected pcDNA-ANCR or si-ANCR into THP-1 cells, the ability of LncRNA ANCR to bind to IL-1β and IL-6 promoter was detected by ChIP and qRT-PCR (TIFF 105 kb)

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Xie, C., Guo, Y. & Lou, S. LncRNA ANCR Promotes Invasion and Migration of Gastric Cancer by Regulating FoxO1 Expression to Inhibit Macrophage M1 Polarization. Dig Dis Sci 65, 2863–2872 (2020). https://doi.org/10.1007/s10620-019-06019-1

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  • DOI: https://doi.org/10.1007/s10620-019-06019-1

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