LncRNA ANCR Promotes Invasion and Migration of Gastric Cancer by Regulating FoxO1 Expression to Inhibit Macrophage M1 Po
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ORIGINAL ARTICLE
LncRNA ANCR Promotes Invasion and Migration of Gastric Cancer by Regulating FoxO1 Expression to Inhibit Macrophage M1 Polarization Chunying Xie1 · Yanyan Guo1 · Siyuan Lou2 Received: 21 June 2019 / Accepted: 17 December 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Gastric cancer · LncRNA ANCR · FoxO1 · Invasion and migration
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-019-06019-1) contains supplementary material, which is available to authorized users. * Siyuan Lou [email protected] 1
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Min‑De Road, Nanchang 330006, Jiangxi Province, China
2
Gastric cancer (GC) is the fifth most common cancer worldwide, and the third most common cause of death from cancer [1]. Although the treatment of GC has made significant progress in recent decades, after curative resection and adjuvant treatment, patients with GC still have severe metastasis. Due to tumor recurrence and metastasis, the long-term survival rate of patients with GC is not considerable, which is a suitable challenge for GC treatment [2, 3]. However, the mo
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