The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells

• Published in: Oncology reports Vol. 27; no. 1; pp. 10 - 16
• Main Authors: RHODES, Lyndsay V, NITSCHKE, Ashley M, COLLINS-BUROW, Bridgette M, SEGAR, H. Chris, MARTIN, Elizabeth C, DRIVER, Jennifer L, ELLIOTT, Steven, SEUNG YOON NAM, MENG LI, NEPHEW, Kenneth P, BUROW, Matthew E
• Format: Journal Article
• Language: English
• Published: Athens Spandidos 01.01.2012
• Subjects: Apoptosis - drug effects; Biological and medical sciences; Breast Neoplasms - genetics; Cell Line, Tumor; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Female; Gene Expression - drug effects; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Histone Deacetylase Inhibitors - pharmacology; Humans; Hydroxamic Acids - pharmacology; Mammary gland diseases; Medical sciences; MicroRNAs - biosynthesis; Oligonucleotide Array Sequence Analysis; Tumors; Histone deacetylase; Treatment resistance; Breast disease; RNA interference; trichostatin A; MCF-7; Micro RNA; Breast cancer; Malignant tumor; Mammary gland diseases; Gene silencing; Histone deacetylase inhibitor; Cancerology; Cell death; Established cell line; microRNA; drug resistance; Tumor cell; Cancer; Apoptosis
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2011.1488

The development of drug resistance represents a major complication in the effective treatment of breast cancer. Epigenetic therapy, through the use of histone deacetylase inhibitors (HDACi) or demethylation agents, is an emerging area of therapeutic targeting in a number of ontological entities, particularly in the setting of aggressive therapy-resistant disease. Using the well-described HDAC inhibitor trichostatin A (TSA) we demonstrate the suppression of in vitro clonogenicity in the previously described apoptosis-resistant MCF-7TN-R breast carcinoma cell line. Additionally, recent work has demonstrated that these agents can alter the expression profile of microRNA signatures in malignant cells. Using an unbiased microRNA microarray analysis, changes in miRNA expression of MCF-7TN-R cells treated with TSA for 24 h were analyzed. We observed significant up-regulation of 22 miRNAs and down-regulation of 10 miRNAs in response to TSA treatment. Our results demonstrate that the HDACi, TSA, exerts anticancer activity in the apoptosis-resistant MCF-7TN-R breast carcinoma cell line. This activity is correlated with TSA alteration of microRNA expression profiles indicative of a less aggressive phenotype.