Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, PR China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, People's Republic of China.
Gastric Cancer. 2020 Nov;23(6):1018-1032. doi: 10.1007/s10120-020-01091-3. Epub 2020 Jun 24.
Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown.
HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas.
We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1-mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC.
HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.
新兴研究表明，HOTAIR 在胃癌（GC）中作为癌基因发挥作用。然而，其在细胞外基质和肿瘤免疫浸润中的作用尚不清楚。
通过生物信息学分析分析和 qRT-PCR、western blot 和免疫组化检测验证 HOTAIR 和 COL5A1 水平。通过生物信息学分析预测 HOTAIR/miR-1277-5p/COL5A1 轴组分的调控关系及其在 GC 中的作用，并通过体外和体内实验进行验证。通过生物信息学分析评估 COL5A1 与 GC 免疫浸润的相关性，并使用来自癌症基因组图谱的胃腺癌数据集建立基于 COL5A1 的预测列线图。
与正常对照相比，我们发现 HOTAIR 和 COL5A1 在 GC 中高表达，这预示着预后不良。证明了 HOTAIR/miR-1277-5p/COL5A1 轴在 GC 中的调控关系，发现 HOTAIR 和 COL5A1 促进 GC 生长，而 miR-1277-5p 则产生相反的效果。此外，COL5A1 与肿瘤纯度呈负相关，与免疫浸润呈正相关，这表明 COL5A1 介导的 GC 生长可能部分通过调节免疫浸润来实现。此外，建立的基于 COL5A1 的列线图表明，COL5A1 可作为 GC 的预后生物标志物。
HOTAIR 通过海绵 miR-1277-5p 上调 COL5A1 来调节 GC 生长，COL5A1 介导的 GC 细胞增殖可能通过对肿瘤微环境的影响来实现，这为 GC 治疗提供了新的靶点。
