title: MicroRNA profiling of novel African American and Caucasian Prostate Cancer cell lines reveals a reciprocal regulatory relationship of miR-152 and DNA methyltranferase 1.
abstract: miRNA expression in African American compared to Caucasian PCa patients has not been widely explored. Herein, we probed the miRNA expression profile of novel AA and CA derived prostate cancer cell lines. We found a unique miRNA signature associated with AA cell lines, independent of tumor status. Evaluation of the most differentially expressed miRNAs showed that miR-132, miR-367b, miR-410, and miR-152 were decreased in more aggressive cells, and this was reversed after treatment of the cells with 5-aza-2'-deoxycytidine. Sequencing of the miR-152 promoter confirmed that it was highly methylated. Ectopic expression of miR-152 resulted in decreased growth, migration, and invasion. Informatics analysis of a large patient cohort showed that decreased miR-152 expression correlated with increased metastasis and a decrease in biochemical recurrence free survival. Analysis of 39 prostate cancer tissues with matched controls (20 AA and 19 CA), showed that 50% of AA patients had statistically significant lower miR-152 expression compared to only 35% of CA patients. Ectopic expression of miR-152 in LNCaP, PC-3, and MDA-PCa-2b cells down-regulated DNA (cytosine-5)-methyltransferase 1 (DNMT1) through direct binding in the DNMT1 3'UTR. There appeared to be a reciprocal regulatory relationship of miR-152/DNMT1 expression, as cells treated with siRNA DNMT1 caused miR-152 to be re-expressed in all cell lines. In summary, these results demonstrate that epigenetic regulation of miR-152/DNMT1 may play an important role in multiple events that contribute to the aggressiveness of PCa tumors, with an emphasis on AA PCa patients .
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL.
authors.forename: Shaniece C
authors.initials: SC
authors.lastname: Theodore
authors.forename: Melissa
authors.initials: M
authors.lastname: Davis
authors.forename: Fu
authors.initials: F
authors.lastname: Zhao
authors.forename: Honghe
authors.initials: H
authors.lastname: Wang
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.forename: Johng
authors.initials: J
authors.lastname: Rhim
authors.forename: Windy
authors.initials: W
authors.lastname: Dean-Colomb
authors.forename: Timothy
authors.initials: T
authors.lastname: Turner
authors.forename: Weidong
authors.initials: W
authors.lastname: Ji
authors.forename: Guohua
authors.initials: G
authors.lastname: Zeng
authors.forename: William
authors.initials: W
authors.lastname: Grizzle
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL.
authors.forename: Clayton
authors.initials: C
authors.lastname: Yates
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: C550856:MIRN152 microRNA, human; D035683:MicroRNAs; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human