Chunying Xie1, Yanyan Guo1, Siyuan Lou2. 1. Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. 2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Min-De Road, Nanchang, 330006, Jiangxi Province, China. Xcy66699@163.com.
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.
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.
Entities:
Keywords:
FoxO1; Gastric cancer; Invasion and migration; LncRNA ANCR
Authors: Dina Mofed; Jihad I Omran; Salwa Sabet; Ahmed A Baiomy; Marwan Emara; Tamer Z Salem Journal: Mol Biol Rep Date: 2022-10-07 Impact factor: 2.742