Open AccessMiR-7 Promotes Epithelial Cell Transformation by Targeting the Tumor Suppressor KLF4
Author(s) -
Karla F. Meza-Sosa,
Erick I. Pérez-García,
Nohemí Camacho-Concha,
Oswaldo López-Gutiérrez,
Gustavo PedrazaAlva,
Leonor Pérez-Martı́nez
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0103987
Subject(s) - oncomir , klf4 , microrna , microbiology and biotechnology , biology , cell growth , transcription factor , regulation of gene expression , cell , cell cycle , malignant transformation , cancer research , gene , genetics , sox2
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.