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

ABSTRACT: 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.

SUBMITTER: Meza-Sosa KF

PROVIDER: S-EPMC4151986 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Meza-Sosa Karla F KF Pérez-García Erick I EI Camacho-Concha Nohemí N López-Gutiérrez Oswaldo O Pedraza-Alva Gustavo G Pérez-Martínez Leonor L

PloS one 20140902 9

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 ...[more]

PMID: 25181544

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

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

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