HDACs control RUNX2 expression in cancer cells through redundant and cell context-dependent mechanisms

Journal of Experimental & Clinical Cancer Research : CR
Gloria ManzottiAlessia Ciarrocchi

Abstract

RUNX2 is a Runt-related transcription factor required during embryogenesis for skeletal development and morphogenesis of other organs including thyroid and breast gland. Consistent evidence indicates that RUNX2 expression is aberrantly reactivated in cancer and supports tumor progression. The mechanisms leading to RUNX2 expression in cancer has only recently began to emerge. Previously, we showed that suppressing the activity of the epigenetic regulators HDACs significantly represses RUNX2 expression highlighting a role for these enzymes in RUNX2 reactivation in cancer. However, the molecular mechanisms by which HDACs control RUNX2 are still largely unexplored. Here, to fill this gap, we investigated the role of different HDACs in RUNX2 expression regulation in breast and thyroid cancer, tumors that majorly rely on RUNX2 for their development and progression. Proliferation assays and evaluation of RUNX2 mRNA levels by qRT-PCR were used to evaluate the effect of several HDACi and specific siRNAs on a panel of cancer cell lines. Moreover, ChIP and co-IP assays were performed to elucidate the molecular mechanism underneath the RUNX2 transcriptional regulation. Finally, RNA-sequencing unveiled a new subset of genes whose transcript...Continue Reading

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Citations

May 8, 2020·International Journal of Molecular Sciences·Duk-Hwa KwonHyun Kook
May 1, 2021·Frontiers in Oncology·Valentina FragliassoAlessia Ciarrocchi

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Methods Mentioned

BETA
acetylation
transfection
PCR
RNA-Seq
immunoprecipitation
co-immunoprecipitation
Protein Assay
ChIP
co-IP
histone acetylation

Software Mentioned

ggpubr
TCGAbiolinks ”
R
GraphPad
GraphPad Prism
R library “
Cufflink

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