DDX24 exacerbates inflammation-induced immunosuppression in oral squamous cell carcinoma progression through IL-17 signaling pathway.

OBJECTIVE

DEAD-box ATPase 24 (DDX24) plays crucial roles in the development and progression of cancers, including oral squamous cell carcinoma (OSCC). However, its regulatory mechanism and functional role remain unclear. This study aims to investigate the regulatory mechanism of DDX24 in OSCC.

DESIGN

DDX24 expression and its clinical significance in OSCC and normal tissues were analyzed through bioinformatics analysis. Small interfering RNA (siRNA) was utilized to knockdown (KD) DDX24 expression in CAL27 cells, and assessed biological functions using CCK8, wound healing assays and transwell assay. RNA sequencing was further employed to elucidate the molecular mechanisms underlying DDX24 promotes malignant phenotypes in OSCC. A stable DDX24 knockdown cell line was established, and inflammatory factors expression were quantified by quantitative PCR. An OSCC mouse xenograft model was developed to evaluate the effects of DDX24 knockdown on tumor growth and the immune microenvironment in vivo. Clinical validation pinpoints the importance of the DDX24/ Interleukin-17(IL-17) axis in OSCC using tissue microarray analysis.

RESULTS

DDX24 expression correlates with poor prognosis and reduced survival in OSCC patients. DDX24 KD inhibits OSCC proliferation in vitro and in vivo. RNA sequencing analysis revealed that DDX24 KD markedly attenuated the activity of the IL-17 signaling pathway. Mechanistically, DDX24 facilitates the malignant progression of OSCC by regulating inflammatory factor secretion via the IL-17 signaling pathway, thereby exacerbating tumor-associated inflammation and promoting an immunosuppressive tumor microenvironment.

CONCLUSION

This study identifies the DDX24/IL-17 axis as a key promoter of OSCC progression and provides a theoretical basis for developing targeted therapies.