DDX27 in cancer: molecular mechanisms, clinical implications, and therapeutic potential

DDX27, a member of the DEAD-box RNA helicase family, plays a pivotal role in RNA metabolism and is essential for diverse cellular processes, including transcription, pre-mRNA splicing, translation, and ribosome biogenesis. Recent findings have implicated DDX27 as a substantial contributor to tumorigenesis and cancer progression across various malignancies, establishing its significance as a molecular hub that interacts with key oncogenic partners such as major vault protein (MVP) and nucleophosmin 1 (NPM1).

We conducted systematic search in the following comprehensive academic databases: PubMed, MEDLINE or Web of Science. The keywords such as DDX27, DEAD-box protein 27, RNA helicase DDX27 and cancer, tumor or carcinoma were used for searching. This review consolidates the existing literature on DDX27, examining its structural features and biological functions within the context of tumorigenesis. We systematically explore the molecular mechanisms by which DDX27 influences tumor development and progression, focusing particularly on its roles across different cancer types, including colorectal cancer (CRC), gastric cancer (GC), breast cancer (BC), hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC). Key molecular mechanisms such as NF-κB activation and ERK1/2 phosphorylation involved in DDX27-related pathways are discussed.

Our comprehensive summary elucidates the context-dependent roles of DDX27 across various cancers, highlighting its associations with advanced disease stages, metastasis, and therapeutic resistance. We also assess the potential of DDX27 as a diagnostic and prognostic biomarker, correlating its expression levels with negative clinical outcomes.

Novel therapeutic strategies targeting DDX27 are proposed, including RNA interference techniques (siRNA and shRNA), miRNA-based therapies (miR-617 mimics), pathway modulation, and synthetic lethality approaches. Furthermore, we identify notable limitations in current research surrounding DDX27 and offer potential avenues for future investigation. These innovative strategies present significant promise for the development of precision cancer therapies aimed at improving treatment outcomes for patients.