GATA4 Ubiquitinated by CRL4B complex to stimulated Lysosome and promote Ovarian cancer EMT process [ChIP-seq]

GATA4 has emerged as a prominent transcription active factor for cardiomyogenesis and carcinogenesis. Ovarian cancer is a lethal cancer for women due to the hard diagnosis and easy metastasis. However, the role of GATA4 in breast cancer metastasis remains poorly understood. Here, we indicated that GATA4 was decreased in ovarian cancer and associated with excessive lysosome function and epithelial-mesenchymal transition (EMT). Mechanically, GATA4 was ubiquitinated by CUL4B, a submit of Cullin-Ring E3 ligase (CRL) complexes, and decreased the histone H3K27 acetylation. In vivo, knock down GATA4 was facilitated the proliferation and metastasis of SKOV3. RNA-seq and CUT&Tag ChIP-seq of the transcriptional target of the GATA4 and GATA4/CUL4B complex identified a cohort of genes including TRM22 and KLK15 that are potential involved in lysosome and EMT. These results suggest that GATA4 as a tumor suppressor to impair the lysosome acid environment and promote ovarian cancer metastasis in vivo and vitro through ubiquitin degradation system initiated by CRL4B complex. Our study supporting the tumor suppression role of GATA4, implied the pursuit of GATA4 as a therapeutic target for cancer intervention. Overall design: To investagate the target genes of GATA4 and CUL4B in regulation of ovarian cancer, CUT&Tag ChIP-seq for GATA4 and CUL4B was performed in SKOV3 cells