DDX5 overexpression

The knockdown of DDX5 promotes, while the overexpression of DDX5 inhibits, tongue cancer proliferation, development, and cisplatin resistance...Specifically, the expression of DDX5 is associated with the reduced infiltration of M2 macrophages and increased infiltration of T cell clusters, which may contribute to anticancer effects in the tumor microenvironment. In this study, we establish DDX5 as a valuable prognostic biomarker and an important tumor suppressor in tongue cancer.

Consequently, AURKAIP1 silencing suppressed the activity of Wnt/β-catenin signaling in a DDX5-dependent manner. Our study may primarily disclose the molecular mechanism by which AURKAIP1/DDX5/β-catenin axis modulated TNBC progression, indicating that AURKAIP1 might serve as a therapeutic target as well as a TNBC-specific biomarker for prognosis.

Conversely, overexpression of DDX5 in vivo enhances the anti-tumor efficacy of sorafenib by suppressing Wnt/β-catenin activation and induction of ferroptosis. Thus, DDX5 overexpression in combination with mTKIs is a promising therapeutic strategy for HCC.

Thiostrepton delineated the effect of FOXM1 inhibition on cell proliferation and migration. Colony formation assay, migration assay, and cell cycle data reveal the importance of the DDX5 (p68)/β-catenin/FOXM1 axis in oncogenesis. Collectively, our study mechanistically highlights the regulation of FOXM1 gene expression by DDX5 (p68) and β-catenin in colorectal cancer.

Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.

The Heat Shock Protein 27 (Hsp27) has emerged as a principal factor of the Castration-Resistant Prostate Cancer (CRPC) progression, also, an Antisense Oligonucleotide (ASO) against Hsp27 (OGX-427 or Apatorsen) has been assessed in different clinical trials...We first present the interactions of DDX5 and the Ku70/80 heterodimer and the transcription factor IIH (TFIIH), thereby uncovering DDX5 roles in different DNA repair pathways. Collectively, our study highlights critical functions of DDX5 contributing to CRPC progression and provides preclinical proof-of-concept that a combination of ASO-directed DDX5 inhibition with a DNA damage-inducing therapy can serve as a highly potential novel strategy to treat CRPC.

These findings provide new mechanistic insight into the role of DDX5 in mTORC1 regulation and NASH progression, as well as suggest a number of new targets and a promising lead compound for therapeutic interventions against NASH.

DDX5 is a bona fide FL118 direct target and can act as a biomarker for predicting PDAC and CRC tumour sensitivity to FL118. This would greatly impact FL118 precision medicine for patients with advanced PDAC or advanced CRC in the clinic. FL118 may act as a 'molecular glue degrader' to directly glue DDX5 and ubiquitination regulators together to degrade DDX5.

Moreover, activation of Wnt/β-catenin signaling retarded the anti-tumor activity of KAP-1 knockdown. In conclusion, the data in this study disclosed that KAP-1 silence helped to repress the cell proliferation, migration and invasion by degrading DDK5, so as to hinder the development of thyroid cancer.