SETDB1 regulates SMAD7 expression for breast cancer metastasis |
Tae Young Ryu1,#, Kwangho Kim1,#, Seon-Kyu Kim1, Jung-Hwa Oh2, Jeong-Ki Min1, Cho-Rok Jung1, Mi-Young Son1, Hyun-Soo Cho1,*, Dae-Soo Kim1, Hyun-Soo Cho1,* |
1Korea Research Institute of Bioscience and Biotechnology, 2Korea Institute of Toxicology |
Abstract
Breast cancer (BRC) is the most invasive cancer in women. Although the survival rate of BRC is gradually increasing due to improved screening systems, development of novel therapeutic targets for inhibition of BRC proliferation, metastasis and recurrence have been constantly needed. Thus, in this study, we identified overexpression of SETDB1, a histone methyltransferase, in RNA-seq data of BRC derived from TCGA portal. In Gene Ontology (GO) analysis, cell migration-related GO terms were enriched, and we confirmed down-regulation of cell migration/invasion and alteration of EMT /MET markers after knockdown of SETDB1. Moreover, gene network analysis showed that SMAD7 expression is regulated by SETDB1 levels, indicating that up-regulation of SMAD7 by SETDB1 knockdown inhibited BRC metastasis. Therefore, development of SETDB1 inhibitors and functional studies may help develop more effective clinical guidelines for BRC treatment.
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Abstract, Accepted Manuscript(in press) [Submitted on October 5, 2018, Accepted on December 3, 2018] |
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