BioProject

GATA4 is frequently epigenetically silenced in lung cancers. However, the impact of GATA4 inactivation on tumorigenesis and related therapeutic strategy remain to be determined. More...

GATA4 is frequently epigenetically silenced in lung cancers. However, the impact of GATA4 inactivation on tumorigenesis and related therapeutic strategy remain to be determined. Through the genome-wide screening of tumor suppressing transcription factors, we demonstrate that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vitro. Interestingly, ectopic GATA4 expression resulted in cellular senescence. Mechanistically, GATA4 up-regulates multiple miRNAs (miRNA-32, miRNA-301b, miR-320a, and miR-590) targeting TGFB2 mRNA and causes ensuing downregulation of WNT7B level to induce senescence. TGFBRI inhibitor synergizes with MEK1/2 inhibitor to promote lung cancer regression in Kras G12D/GATA4-/- mouse models. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGFB2 level and is significantly associated with poor prognosis. Overall design: Compare the mRNA profiles in dox and vehicle induced A549i cell by Illumina sequencing Less...