Histone deacetylase inhibition in colorectal cancer cells reveals competing roles for members of the oncogenic miR-17-92 cluster

Diet‐derived butyrate, a histone deacetylase inhibitor (HDI), decreases proliferation and increases apoptosis in colorectal cancer (CRC) cells via epigenetic changes in gene expression. Other HDIs such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) have similar effects. This stud...

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Veröffentlicht in:	Molecular carcinogenesis 2013-06, Vol.52 (6), p.459-474
Hauptverfasser:	Humphreys, Karen J., Cobiac, Lynne, Le Leu, Richard K., Van der Hoek, Mark B., Michael, Michael Z.
Format:	Artikel
Sprache:	eng
Schlagworte:	Adaptor Proteins, Signal Transducing - genetics Adenocarcinoma - drug therapy Adenocarcinoma - genetics Apoptosis Regulatory Proteins - genetics Bcl-2-Like Protein 11 butyrate Butyric Acid - pharmacology Cells Colorectal cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Cyclin-Dependent Kinase Inhibitor p21 - genetics Down-Regulation - drug effects epigenetic Gene expression Gene Expression Regulation, Neoplastic - drug effects HCT116 Cells histone deacetylase inhibitors Histone Deacetylase Inhibitors - pharmacology HT29 Cells Humans Hydroxamic Acids - pharmacology Membrane Proteins - genetics microRNAs MicroRNAs - genetics miR-17-92 Oncology Phosphoproteins - genetics Proto-Oncogene Proteins - genetics PTEN Phosphohydrolase - genetics Ribonucleic acid RNA RNA, Messenger - genetics Transfection Vorinostat
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Zusammenfassung:	Diet‐derived butyrate, a histone deacetylase inhibitor (HDI), decreases proliferation and increases apoptosis in colorectal cancer (CRC) cells via epigenetic changes in gene expression. Other HDIs such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) have similar effects. This study examined the role of microRNAs (miRNAs) in mediating the chemo‐protective effects of HDIs, and explored functions of the oncogenic miR‐17‐92 cluster. The dysregulated miRNA expression observed in HT29 and HCT116 CRC cells could be epigenetically altered by butyrate, SAHA and TSA. These HDIs decreased expression of miR‐17‐92 cluster miRNAs (P
ISSN:	0899-1987 1098-2744
DOI:	10.1002/mc.21879