MiR-7 promotes epithelial cell transformation by targeting the tumor suppressor KLF4

• Published in: PloS one Vol. 9; no. 9; p. e103987
• Main Authors: Meza-Sosa, Karla F, Pérez-García, Erick I, Camacho-Concha, Nohemí, López-Gutiérrez, Oswaldo, Pedraza-Alva, Gustavo, Pérez-Martínez, Leonor
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.09.2014; Public Library of Science (PLoS)
• Subjects: 3' Untranslated Regions - genetics; Animals; Base Sequence; Binding Sites; Biology and life sciences; Breast cancer; Cancer; Carcinogens; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Colorectal cancer; Conserved Sequence - genetics; Cyclin D; Cyclin D - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Down-Regulation - genetics; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Esophagus; Evolution, Molecular; Gene expression; Gene Expression Regulation, Neoplastic; Gene regulation; Genetic transformation; Homeostasis; Humans; KLF4 protein; Kruppel-Like Transcription Factors - metabolism; Lungs; Male; Melanoma; Metastasis; Mice, Nude; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Molecular modelling; Molecular Sequence Data; Post-transcription; Protein Binding - genetics; Proteins; Rodents; S Phase - genetics; Signaling; Skin; Transformation; Tumor Stem Cell Assay; Tumor suppressor genes; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0103987

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression and their misregulation is common in different types of cancer. Although it has been shown that miR-7 plays an oncogenic role in different cellular contexts, the molecular mechanisms by which miR-7 promotes cell transformation are not well understood. Here we show that the transcription factor KLF4 is a direct target of miR-7 and present experimental evidence indicating that the regulation of KLF4 by miR-7 has functional implications in epithelial cell transformation. Stable overexpression of miR-7 into lung and skin epithelial cells enhanced cell proliferation, cell migration and tumor formation. Alteration of these cellular functions by miR-7 resulted from misregulation of KLF4 target genes involved in cell cycle control. miR-7-induced tumors showed decreased p21 and increased Cyclin D levels. Taken together, these findings indicate that miR-7 acts as an oncomiR in epithelial cells in part by directly regulating KLF4 expression. Thus, we conclude that miR-7 acts as an oncomiR in the epithelial cellular context, where through the negative regulation of KLF4-dependent signaling pathways, miR-7 promotes cellular transformation and tumor growth.