Department of Gastroenterology, Yantai Yuhuangding Hospital, Yantai, Shandong, People's Republic of China.
Central Laboratory, Yantai Yuhuangding Hospital, Yantai, Shandong, People's Republic of China.
Life Sci. 2021 Aug 1;278:119522. doi: 10.1016/j.lfs.2021.119522. Epub 2021 Apr 21.
This study aimed at exploring HOXB13 expression and function in gastric cancer (GC), and the underlying molecular mechanism.
HOXB13 and fat mass and obesity-associated protein (FTO) expression in GC and non-GC tissues of GC patients were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting. The regulatory relationship between FTO and HOXB13 was verified via RT-qPCR, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and double luciferase reporter gene assay. The effects of HOXB13 and FTO on proliferation, invasion, and migration of GC cells were studied using EdU and Transwell assays.
HOXB13 and FTO expression was abnormally high in GC tissues and cell lines, with no significant correlation between HOXB13 and FTO expression and the prognosis of GC patients. Inhibiting FTO expression in GC cells decreased HOXB13 methylation and upregulated HOXB13 expression. Inhibiting HOXB13 and FTO expression suppressed GC cell proliferation, migration, and invasion. Decreased HOXB13 expression suppressed PI3K/AKT/mTOR signaling pathway activity, while atypical HOXB13 expression promoted it. A probable downstream target of HOXB13 was insulin-like growth factor 1 receptor (IGF-1R); a decrease in IGF-1R relieved GC cell migration, invasion, and proliferation and inhibited PI3K/AKT/mTOR signaling pathway activity promoted by atypical HOXB13 expression.
HOXB13 and FTO expression is elevated in GC. FTO suppresses HOXB13 methylation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R. HOXB13 and associated signaling pathways can be effective targets for GC therapy.
本研究旨在探讨 HOXB13 在胃癌（GC）中的表达和功能及其潜在的分子机制。
使用基因表达谱分析交互分析（GEPIA）分析 GC 患者 GC 组织和非 GC 组织中 HOXB13 和脂肪量和肥胖相关蛋白（FTO）的表达，并通过定量逆转录-聚合酶链反应（RT-qPCR）和蛋白质印迹法进行验证。通过 RT-qPCR、甲基化 RNA 免疫沉淀测序（MeRIP-seq）和双荧光素酶报告基因检测验证 FTO 和 HOXB13 之间的调控关系。使用 EdU 和 Transwell 测定法研究 HOXB13 和 FTO 对 GC 细胞增殖、侵袭和迁移的影响。
HOXB13 和 FTO 在 GC 组织和细胞系中的表达异常升高，HOXB13 和 FTO 表达与 GC 患者的预后无显著相关性。在 GC 细胞中抑制 FTO 表达可降低 HOXB13 甲基化并上调 HOXB13 表达。抑制 HOXB13 和 FTO 表达可抑制 GC 细胞增殖、迁移和侵袭。HOXB13 表达降低可抑制 PI3K/AKT/mTOR 信号通路活性，而非典型 HOXB13 表达则促进其活性。HOXB13 的一个可能下游靶标是胰岛素样生长因子 1 受体（IGF-1R）；降低 IGF-1R 可缓解由非典型 HOXB13 表达促进的 GC 细胞迁移、侵袭和增殖，并抑制 PI3K/AKT/mTOR 信号通路活性。
HOXB13 和 FTO 在 GC 中表达升高。FTO 抑制 HOXB13 甲基化；FTO 和 HOXB13 表达促进 GC 细胞增殖、迁移和侵袭。HOXB13 表达通过 IGF-1R 加剧 GC 侵袭，通过 PI3K/AKT/mTOR 信号通路。HOXB13 及其相关信号通路可作为 GC 治疗的有效靶点。
