LncRNA938/ TAF9/TTK axis promotes EMT and serves as a therapeutic target in hepatoblastoma.

BACKGROUND

Hepatoblastoma (HB) is the most common malignant liver tumor in children. The expression of TAF9 is frequently upregulated in HB; however, its underlying molecular mechanisms are not yet fully understood, and its potential as a therapeutic target warrants further investigation.

METHODS

Bioinformatic analysis was performed using sequencing datas to evaluate clinical diagnostic and prognostic values of molecules. Biological functions were assessed using in vitro and in vivo experiments. Various techniques, including quantitative PCR, western blotting, immunohistochemistry, RNA immunoprecipitation, RNA pull-down, immunofluorescence, and luciferase reporter assays, were used to investigate the underlying molecular mechanisms.

RESULTS

TAF9 was significantly overexpressed in HB tissues and correlated with poor prognosis. Both lncRNA938 and TAF9 promoted HB proliferation and metastasis. Mechanistically, lncRNA938 directly bound TAF9 and regulated its nuclear localization, while TAF9 activated TTK transcription via promoter binding. TTK inhibitors effectively reversed the epithelial-mesenchymal transition and malignant phenotypes induced by TAF9 overexpression.

CONCLUSION

The lncRNA938-TAF9-TTK axis is a critical driver of HB progression. Targeting this axis, particularly through TTK inhibition, represents a novel therapeutic strategy against HB.