Transcriptomics,Genomics

Dataset Information

45

Cluster regulation of RUNX family by "gene switch" triggers a profound tumor regression of diverse origins.


ABSTRACT: Although Runt-related transcription factor 1 (RUNX1) has been generally considered to be a tumor suppressor, a growing body of evidence strongly suggests its pro-oncogenic property in acute myeloid leukemia (AML), Here we demonstrate that anti-leukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Based on our present findings, anti-tumor effect elicited by RUNX1 silencing was compensated by the other RUNX family members such as RUNX2 and RUNX3, and a simultaneous attenuation of whole RUNX family members as a cluster displayed a much stronger anti-tumor effect relative to their individual suppression. Notably, switching off RUNX cluster utilizing the novel alkylating agent-conjugated pyrrole-imidazole (PI) polyamides, which specifically bound to the consensus RUNX-binding sequences, was highly effective against leukemia as well as dismal-prognostic solid tumors arising from diverse origins in vivo without any significant adverse events. Together, this work identifies the crucial role of RUNX cluster in the maintenance and the progression of cancer cells, and the indicated gene switch technology-dependent its modulation would be a novel strategy to control malignancies. Overall design: Genome-wide gene expression change by knockdown of RUNX family genes or alkylating PIP conjugates were examined.

INSTRUMENT(S): [HuGene-2_1-st] Affymetrix Human Gene 2.1 ST Array [transcript (gene) version]

SUBMITTER: Junichi Taniguchi  

PROVIDER: GSE94835 | GEO | 2017-03-26

SECONDARY ACCESSION(S): PRJNA374547

REPOSITORIES: GEO

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