title: Down-regulation of miRNA-106b inhibits growth of melanoma cells by promoting G1-phase cell cycle arrest and reactivation of p21/WAF1/Cip1 protein.
abstract: MiR-106b is overexpressed in various types of cancers and is associated with the regulation of the carcinogenic processes. Using RT-PCR, we have identified overexpression of miRNA-106b in various melanoma cell lines (A375, Hs294t, SK-Mel28, SK-Mel 119, Mel 1241, Mel 1011 and Mel 928) as compared to its expression in normal human epidermal melanocytes (NHEM). The overexpression of miR-106b in melanoma cells (A375, Hs294t) was associated with greater cell proliferation capacity than NHEM. Treatment of A375 and Hs294t cells with anti-miR-106b resulted in inhibition of cell proliferation as well as G1-phase arrest. We determined the effects of grape seed proanthocyanidins (GSPs) on the expression of miRNA-106b and its underlying molecular targets. Treatment of A375 and Hs294t cells with GSPs resulted in suppression of the levels of miRNA-106b, cytotoxicity, G1-phase arrest and reactivation of p21/WAF1/Cip1. Dietary GSPs significantly inhibited growth of A375 melanoma cell tumor xenografts in nude mice, which was associated with reduction in the levels of miRNA-106b, tumor cell proliferation and increases in the levels of p21/WAF1/Cip1 protein. These studies suggest that miRNA-106b plays a crucial role in melanoma growth and that GSPs act as an inhibitor of miR-106b thereby blocking melanoma growth in vitro and in vivo models.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA. Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA. Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D044945:Proanthocyanidins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53