title: Mir-33 regulates cell proliferation and cell cycle progression.
abstract: Cholesterol metabolism is tightly regulated at the cellular level and is essential for cellular growth. microRNAs (miRNAs), a class of noncoding RNAs, have emerged as critical regulators of gene expression, acting predominantly at posttranscriptional level. Recent work from our group and others has shown that hsa-miR-33a and hsa-miR-33b, miRNAs located within intronic sequences of the Srebp genes, regulate cholesterol and fatty acid metabolism in concert with their host genes. Here, we show that hsa-miR-33 family members modulate the expression of genes involved in cell cycle regulation and cell proliferation. MiR-33 inhibits the expression of the cyclin-dependent kinase 6 (CDK6) and cyclin D1 (CCND1), thereby reducing cell proliferation and cell cycle progression. Overexpression of miR-33 induces a significant G 1 cell cycle arrest in Huh7 and A549 cell lines. Most importantly, inhibition of miR-33 expression using 2'fluoro/methoxyethyl-modified (2'F/MOE-modified) phosphorothioate backbone antisense oligonucleotides improves liver regeneration after partial hepatectomy (PH) in mice, suggesting an important role for miR-33 in regulating hepatocyte proliferation during liver regeneration. Altogether, these results suggest that Srebp/miR-33 locus may cooperate to regulate cell proliferation, cell cycle progression and may also be relevant to human liver regeneration.
authors.affiliation: Department of Medicine, Leon H. Charney Division of Cardiology and Cell Biology and Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cirera-Salinas
authors.forename: Montse
authors.initials: M
authors.lastname: Pauta
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Allen
authors.forename: Alessandro G
authors.initials: AG
authors.lastname: Salerno
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Ramírez
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Chamorro-Jorganes
authors.forename: Amarylis C
authors.initials: AC
authors.lastname: Wanschel
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lasuncion
authors.forename: Manuel
authors.initials: M
authors.lastname: Morales-Ruiz
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suarez
authors.forename: Ángel
authors.initials: Á
authors.lastname: Baldan
authors.forename: Enric
authors.initials: E
authors.lastname: Esplugues
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology; D010710:Phosphates / Q000737:chemistry
chemical_list: C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D010710:Phosphates; D019938:Cyclin D1; C083120:phosphorodithioic acid; D051361:Cyclin-Dependent Kinase 6