Reprogramming of lipid metabolism during hepatocarcinogenesis is not well elucidated. Here, we aimed to explore pivotal RNA-binding motif proteins (RBMs) in lipid metabolism and their therapeutic potential in hepatocellular carcinoma (HCC). Through bioinformatic analysis, we identified RBM45 as a critical gene of interest among differentially expressed RBMs in HCC, with significant prognostic relevance. RBM45 influenced the malignant biological phenotype and lipid metabolism of HCC cells. Mechanically, RBM45 promotes de novo lipogenesis in HCC by directly targeting two key enzymes involved in long-chain fatty acid synthesis, ACSL1 and ACSL4. RBM45 also targets Rictor, which has been demonstrated to modulate lipid metabolism profoundly. RBM45 also aided lipid degradation through activating a key fatty acid β oxidation enzyme, CPT1A. Thus, RBM45 boosted lipid synthesis and decomposition, indicating an enhanced utility of lipid fuels in HCC. Clinically, body mass index was positively correlated with RBM45 in human HCCs. The combination of a PI3K/AKT/mTOR pathway inhibitor in vitro or Sorafenib in orthotopic liver cancer mouse models with shRBM45 has a more significant therapeutic effect on liver cancer than the drug alone. In summary, our findings highlight the versatile roles of RBM45 in lipid metabolism reprogramming and its therapeutic potential in HCC.

肝癌发生过程中脂质代谢的重编程尚未得到很好的阐明。在这里，我们的目的是探索脂质代谢中关键的 RNA 结合基序蛋白 (RBM) 及其在肝细胞癌 (HCC) 中的治疗潜力。通过生物信息学分析，我们将 RBM45 确定为 HCC 差异表达 RBM 中的一个关键基因，具有显着的预后相关性。 RBM45影响HCC细胞的恶性生物学表型和脂质代谢。从机械角度来看，RBM45 通过直接靶向参与长链脂肪酸合成的两种关键酶（ACSL1 和 ACSL4），促进 HCC 中的从头脂肪生成。 RBM45 还针对 Rictor，已被证明可以深刻调节脂质代谢。 RBM45 还通过激活关键的脂肪酸 β 氧化酶 CPT1A 来帮助脂质降解。因此，RBM45 促进脂质合成和分解，表明脂质燃料在 HCC 中的效用增强。临床上，人类肝癌中体重指数与RBM45呈正相关。体外PI3K/AKT/mTOR通路抑制剂或原位肝癌小鼠模型中的索拉非尼联合shRBM45对肝癌的治疗效果比单独使用药物更显着。总之，我们的研究结果强调了 RBM45 在脂质代谢重编程中的多功能作用及其在 HCC 中的治疗潜力。