title: MIEN1 is tightly regulated by SINE Alu methylation in its promoter.
abstract: Migration and invasion enhancer 1 (MIEN1) is a novel gene involved in prostate cancer progression by enhancing prostate cancer cell migration and invasion. DNA methylation, an important epigenetic regulation, is one of the most widely altered mechanisms in prostate cancer. This phenomenon frames the basis to study the DNA methylation patterns in the promoter region of MIEN1. Bisulfite pyrosequencing demonstrates the MIEN1 promoter contains a short interspersed nuclear Alu element (SINE Alu) repeat sequence. Validation of methylation inhibition on MIEN1 was performed using nucleoside analogs and non-nucleoside inhibitors and resulted in an increase in both MIEN1 RNA and protein in normal cells. MIEN1 mRNA and protein increases upon inhibition of individual DNA methyltransferases using RNA interference technologies. Furthermore, dual luciferase reporter assays, in silico analysis, and chromatin immunoprecipitation assays identified a sequence upstream of the transcription start site that has a site for binding of the USF transcription factors. These results suggest the MIEN1 promoter has a SINE Alu region that is hypermethylated in normal cells leading to repression of the gene. In cancer, the hypomethylation of a part of this repeat, in addition to the binding of USF, results in MIEN1 expression.
authors: Department of Molecular and Medical Genetics, Institute for Cancer Research and Texas Center for Health Disparities, University of North Texas Health Science Center, Fort Worth, 76107, TX, USA.
authors: Smrithi
authors: S
authors: Rajendiran
authors: Department of Molecular and Medical Genetics, Institute for Cancer Research and Texas Center for Health Disparities, University of North Texas Health Science Center, Fort Worth, 76107, TX, USA.
authors: Lee D
authors: LD
authors: Gibbs
authors: Department of Molecular and Medical Genetics, Institute for Cancer Research and Texas Center for Health Disparities, University of North Texas Health Science Center, Fort Worth, 76107, TX, USA.
authors: Timothy
authors: T
authors: Van Treuren
authors: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, 68198, NE, USA.
authors: David L
authors: DL
authors: Klinkebiel
authors: Department of Molecular and Medical Genetics, Institute for Cancer Research and Texas Center for Health Disparities, University of North Texas Health Science Center, Fort Worth, 76107, TX, USA.
authors: Jamboor K
authors: JK
authors: Vishwanatha
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D063185:Epigenetic Repression / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D051720:Upstream Stimulatory Factors / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C517054:MIEN1 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D051720:Upstream Stimulatory Factors; D015254:DNA Modification Methylases
keywords: DNA methylation; MIEN1; SINE Alu; epigenetic regulation; prostate