Data from: Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

Several homeobox-related gene (HOX) transcription factors such as
mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug
resistance, malignant progression and/or clinical prognostic responses in
lung cancer patients; however, the mechanisms involved in these responses
have yet to be elucidated. Here, an epigenomic strategy was implemented to
identify novel MEOX2 gene promoter transcription targets and propose a new
molecular mechanism underlying lung cancer drug resistance and poor
clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived
from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter
tiling arrays and bioinformatics analyses were performed, and
quantitative, functional and clinical validation were also carried out. We
statistically identified a common profile consisting of 78 gene promoter
targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and
FDR≤0.2). The GLI-1 gene promoter region from -2,192 to -109 was occupied
by MEOX2, accompanied by transcriptionally active RNA Pol II and was
epigenetically linked to the active histones H3K27Ac and H3K4me3; these
associations were quantitatively validated. Moreover, siRNA genetic
silencing assays identified a MEOX2-GLI1 axis involved in cellular
cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as
cellular migration and proliferation. Finally, Kaplan-Maier survival
analyses identified significant MEOX2-dependent GLI-1 protein expression
associated with clinical progression and poorer overall survival using an
independent cohort of NSCLC patients undergoing platinum-based oncological
therapy with both epidermal growth factor receptor (EGFR)-non-mutated and
EGFR-mutated status. In conclusion, this is the first study to investigate
epigenome-wide MEOX2-transcription factor occupation identifying a novel
overexpressed MEOX2-GLI1 axis and its clinical association with
platinum-based cancer drug resistance and EGFR-tyrosine kinase inhibitor
(TKI)-based therapy responses in NSCLC patients.