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Mir-33 regulates cell proliferation and cell cycle progression

2012; Taylor & Francis; Volume: 11; Issue: 5 Linguagem: Inglês

10.4161/cc.11.5.19421

1538-4101

Daniel Cirera‐Salinas, Montse Pauta, Ryan M. Allen, Alessandro G. Salerno, Cristina M. Ramírez, Aránzazu Chamorro‐Jorganes, Amarylis Wanschel, Miguel A. Lasunción, Manuel Morales‐Ruiz, Yajaira Suárez, Ángel Baldán, Enric Esplugues, Carlos Fernández‐Hernando,

Circular RNAs in diseases

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 G1 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.