Multidimensional analysis reveals the potential of ACSL3 as a cancer biomarker: from pan-cancer exploration to functional validation in hepatocellular carcinoma.

ACSL3 converts long-chain fatty acids into acyl-CoA, a key step in lipid metabolism. Since this process is linked to cancer development and progression, this study investigates the specific roles and underlying mechanisms of ACSL3 across various cancer types. We examined ACSL3 by analyzing its expression, transcriptomic variations, single-cell localization, prognostic significance, and biological roles using various databases and perspectives. We also studied its relationship with the immune microenvironment, epigenetic changes, and drug responsiveness. The effects of ACSL3 on liver cancer were investigated through experiments conducted both in vivo and in vitro experiments. ACSL3 was found to be abnormally expressed in most cancers, with a higher expression ratio in macrophages, and is associated with the prognosis of certain cancers, such as kidney cancer, esophageal cancer, head and neck cancer, liver cancer, lung cancer, thyroid cancer, and ovarian/cervical cancer. Its expression is closely linked to immune cell infiltration, the anti-cancer immune cycle, major histocompatibility complex, immune checkpoints, tumor mutation burden, microsatellite instability, RNA modifications like m1A, m5C, and m6A, as well as DNA methylation. ACSL3 is commonly involved in pathways related to the tumor microenvironment and cell cycle across various cancers. Experiments both in vitro and in vivo showed that reducing ACSL3 levels significantly decreased liver cancer cell growth, indicating its potential as a therapeutic target. Our research underscores the promise of ACSL3 expression as a new biomarker for forecasting the outcomes of various human cancers and assessing the effectiveness of immunotherapy.