Tao Li, Guo Yixian, Liu Runkun, Lv Meng, Wang Yufeng
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Funct Integr Genomics. 2025 Jun 3;25(1):117. doi: 10.1007/s10142-025-01626-w.
The involvement of leucine rich repeats protein 1 (LRR1) in various biological processes has been established, but its specific role and potential mechanisms in hepatocellular carcinoma (HCC) remain unclear. The aim of this study was to explore the potential expression, function, and mechanisms of LRR1 in HCC. Data acquired from TCGA, GEO and other online databases was used to investigate the expression and roles of LRR1 in HCC through various approaches, including expression profiling, clinical significance analysis, methylation status examination, immune infiltration assessment, genomic mutation analysis, and pathway network exploration. With findings in bioinformatic analysis, we further validated the involvement of LRR1 in HCC progression by cellular experiments. The expression of LRR1 is significantly upregulated in HCC compared to normal liver tissues and cell line. Additionally, the involvement of LRR1 was implicated in various modifications across diverse aspects associated with HCC. Enrichment analysis indicated that LRR1 was induced by hypoxia in HIF-1-dependent manner. The cell experiments convincingly demonstrated the pivotal role of LRR1 in tumor cell proliferation, migration, invasion and angiogenesis under the regulation of HIF-1. Our findings demonstrate a novel oncogene LRR1 in HCC, which is also a HIF-1 target gene and functions as a promising biomarker and contributes to the hypoxia-induced progression of HCC through a HIF-1/LRR1 manner.
富含亮氨酸重复序列蛋白1(LRR1)参与多种生物学过程已得到证实,但其在肝细胞癌(HCC)中的具体作用和潜在机制仍不清楚。本研究旨在探讨LRR1在HCC中的潜在表达、功能及机制。利用从TCGA、GEO和其他在线数据库获取的数据,通过多种方法研究LRR1在HCC中的表达和作用,包括表达谱分析、临床意义分析、甲基化状态检测、免疫浸润评估、基因组突变分析和通路网络探索。基于生物信息学分析结果,我们通过细胞实验进一步验证了LRR1参与HCC进展。与正常肝组织和细胞系相比,LRR1在HCC中的表达显著上调。此外,LRR1参与了与HCC相关的各个方面的多种修饰。富集分析表明,LRR1在缺氧条件下以HIF-1依赖的方式被诱导。细胞实验令人信服地证明了LRR1在HIF-1调控下对肿瘤细胞增殖、迁移、侵袭和血管生成的关键作用。我们的研究结果表明,LRR1是HCC中的一种新型癌基因,也是一种HIF-1靶基因,并作为一种有前景的生物标志物发挥作用,通过HIF-1/LRR1方式促进HCC的缺氧诱导进展。
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