title: MTA1-activated Epi-microRNA-22 regulates E-cadherin and prostate cancer invasiveness.
abstract: We have previously shown that metastasis-associated protein 1 (MTA1), a chromatin remodeler, plays an important role in prostate cancer invasiveness, likely through regulation of epithelial-to-mesenchymal transition. Here, we identified miR-22 as an epigenetic-microRNA (Epi-miR) directly induced by MTA1 and predicted to target E-cadherin. Loss-of-function and overexpression studies of MTA1 reinforced its regulatory role in miR-22 expression. MiR-22 directly targets the 3'-untranslated region of E-cadherin, and ectopic overexpression of miR-22 diminishes E-cadherin expression. Overexpression of miR-22 in prostate cancer cells promotes cell invasiveness and migration. Meta-analysis of patient tumor samples indicates a positive correlation between MTA1 and miR-22, supporting their inhibitory effect on E-cadherin expression. Our findings implicate the MTA1/Epi-miR-22/E-cadherin axis as a new epigenetic signaling pathway that promotes tumor invasion in prostate cancer.
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|School of Medicine-Department of Radiation/Oncology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Dhar
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|School of Medicine-Department of Radiation/Oncology, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Gomez
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Israh
authors.initials: I
authors.lastname: Akhtar
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Hancock
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Lage
authors.affiliation: Division of Urology, Department of Surgery, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Pound
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.|Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Anait S
authors.initials: AS
authors.lastname: Levenson
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators
chemical_list: D020413:3' Untranslated Regions; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases
keywords: E-cadherin; MTA1; miR-22; prostate cancer