DDX27: An RNA helicase regulating cancer progression and therapeutic prospects

DDX27, a member of the DEAD-box RNA helicase family, plays a crucial role in RNA metabolism, inflammation, and cancer progression. Elevated expression of DDX27 has been observed in multiple cancers, including oral squamous cell carcinoma (OSCC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and hepatocellular carcinoma (HCC), where it is associated with poor prognosis, tumor growth, metastasis, and chemoresistance. DDX27 regulates the NF-κB signaling pathway, which is central to inflammation and tumor progression, and influences key cellular processes such as cell cycle regulation, apoptosis, migration, and stemness. Additionally, DDX27 promotes epithelial-mesenchymal transition (EMT), further contributing to metastasis. Its interactions with non-coding RNAs and various signaling pathways complicate treatment responses, making DDX27 a promising therapeutic target. This review explores the role of DDX27 as both a biomarker and therapeutic target, with potential strategies including small molecule inhibitors, RNA interference, and combination therapies with existing treatments such as NF-κB inhibitors or chemotherapy. Targeting DDX27 may help overcome resistance, reduce metastasis, and improve cancer treatment outcomes. Further research into its molecular mechanisms and interactions will be crucial for developing effective therapies, particularly for cancers with high metastatic potential.