Decoding DDX36 impact in lung cancer: expression, prognostics, and tumor progression

Abstract

DDX36, also known as DHX36, is an ATP-dependent DEAH-box DNA/RNA helicase with high affinity for G-quadruplex (G4) structures and plays an important role in nucleic acid metabolism. Although dysregulation of DDX36 has been implicated in multiple malignancies, its expression pattern and functional relevance in lung cancer have not been comprehensively defined. In this study, we systematically investigated DDX36 expression, prognostics, and its biological function in lung cancer by integrating clinical specimens, publicly available datasets, and complementary in vitro and in vivo models. DDX36 protein expression was frequently elevated in lung cancer tissues compared with adjacent non-tumorous tissues. Integrated mRNA and protein analyses revealed discordant regulation of DDX36, with a consistent increase at the protein level. Elevated DDX36 expression was associated with poor survival. Cell-based functional assays demonstrated that DDX36 contributes to the proliferation, migration, and invasion of lung cancer cells, whereas genetic depletion or silencing of DDX36 attenuated these phenotypes. In xenograft models, both DDX36 silencing and loss-of-function of DDX36 significantly suppressed tumor growth and/or metastasis, including complete suppression of tumor formation observed in a subset of animals. Collectively, these findings indicate that DDX36 contributes to malignant phenotypes and tumor growth in lung cancer, supporting its potential utility clinically as a biologically relevant diagnostic and prognostic biomarker, as well as a candidate therapeutic vulnerability.