title: Emerging role of SETDB1 as a therapeutic target.
abstract: Epigenetic changes lead to aberrant gene expression in cancer. SETDB1, a histone lysine methyltransferase plays an important role in methylation and gene silencing. Aberrant histone methylation at H3K9 by SETDB1 promotes silencing of tumor suppressor genes and thus contributes to carcinogenesis. Recent studies indicate that SETDB1 is abnormally expressed in various human cancer conditions which contributed to enhanced tumor growth and metastasis. Hence, SETDB1 appears to be a promising epigenetic target for therapeutic intervention. Areas covered: In this article, the structural features, localization and functions of SETDB1 are reviewed. Also, an overview of the role of SETDB1 in cancer and other disease mechanisms, the currently studied inhibitors for SETDB1 are mentioned. Expert opinion: Silencing of tumor suppressor genes due to excessive trimethylation at H3K9 by amplified SETDB1 levels is found in various cancerous conditions. Since epigenetic changes are reversible, SETDB1 holds promise as an important therapeutic target for cancer. Therefore, a better understanding of the role of SETDB1 and its interaction with various proteins in cancer-related mechanisms along with therapeutic interventions specific for SETDB1 may improve targeted cancer therapy.
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Archana Venkataramana
authors.initials: AV
authors.lastname: Karanth
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Radhika Radha
authors.initials: RR
authors.lastname: Maniswami
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Seema
authors.initials: S
authors.lastname: Prashanth
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Govindaraj
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Ramya
authors.initials: R
authors.lastname: Padmavathy
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Sooriya Kumar
authors.initials: SK
authors.lastname: Jegatheesan
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
authors.affiliation: a Bioinformatics, Jubilant Biosys Ltd. , Bangalore , India.
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopal
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D011496:Protein Methyltransferases / Q000235:genetics*
chemical_list: D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human
keywords: Cancer; DZNep; H3K9 trimethylation; SETDB1; gene silencing; mithramycin