Department of Hepatobiliary-Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Biomol Biomed. 2024 Sep 6;24(5):1216-1230. doi: 10.17305/bb.2024.10247.
The objective of this research was to investigate the potential mechanisms of AlkB homolog 5, RNA demethylase (ALKBH5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas (TCGA), Kruskal-Wallis method and Kaplan-Meier (KM) survival analysis to study the expression of ALKBH5 and its correlation with clinical factors in HCC. In vitro experiments verified the expression of ALKBH5 and its effect on HCC cell phenotype. We screened differentially expressed genes (DEGs) from HCC patients associated with ALKBH5. Through this screening we identified the downstream gene TTI1 which is associated with ALKBH5 and investigated its function using Gene Expression Profiling Interaction Analysis (GEPIA) along with univariate Cox proportional hazards regression analysis. Finally, we analyzed the functions of ALKBH5 and TTI1 in HCC cells. Across numerous pan-cancer types, we observed significant overexpression of ALKBH5. In vitro experiments confirmed ALKBH5 as an oncogene in HCC, with its knockdown leading to suppressed cell proliferation, migration, and invasion. Bioinformatics analyses also demonstrated a significant positive correlation between ALKBH5 and TTI1. TTI1, highly expressed in cells, showed promising prognostic ability for patients. Further experiments confirmed that suppressing TTI1 impeded cell growth and movement, with this effect partially offset by increased ALKBH5 expression. Conversely, promoting these cellular processes was observed with TTI1 overexpression, but was dampened by decreased ALKBH5 expression. In conclusion, our findings suggest that ALKBH5 may influence proliferation, migration and invasion of HCC by modulating TTI1 expression, providing a new direction for treating HCC.
本研究旨在探讨 AlkB 同源物 5，RNA 去甲基酶（ALKBH5）在肝细胞癌（HCC）中的潜在机制。我们使用癌症基因组图谱（TCGA）、Kruskal-Wallis 方法和 Kaplan-Meier（KM）生存分析来研究 ALKBH5 的表达及其与 HCC 临床因素的相关性。体外实验验证了 ALKBH5 的表达及其对 HCC 细胞表型的影响。我们从与 ALKBH5 相关的 HCC 患者中筛选差异表达基因（DEGs）。通过筛选，我们确定了与 ALKBH5 相关的下游基因 TTI1，并使用基因表达谱交互分析（GEPIA）和单变量 Cox 比例风险回归分析研究其功能。最后，我们分析了 ALKBH5 和 TTI1 在 HCC 细胞中的功能。在多种泛癌类型中，我们观察到 ALKBH5 的显著过表达。体外实验证实 ALKBH5 是 HCC 的致癌基因，其敲低导致细胞增殖、迁移和侵袭受到抑制。生物信息学分析还表明 ALKBH5 和 TTI1 之间存在显著的正相关。在细胞中高表达的 TTI1 对患者具有良好的预后能力。进一步的实验证实，抑制 TTI1 会阻碍细胞生长和运动，而增加 ALKBH5 的表达则部分抵消了这种影响。相反，随着 TTI1 的过表达，观察到这些细胞过程的促进，但随着 ALKBH5 表达的降低，这种促进作用受到抑制。综上所述，我们的研究结果表明，ALKBH5 可能通过调节 TTI1 的表达影响 HCC 的增殖、迁移和侵袭，为治疗 HCC 提供了新的方向。
