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MicroRNA-22 Regulates Hypoxia Signaling in Colon Cancer Cells
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MicroRNA-22 Regulates Hypoxia Signaling in Colon Cancer Cells
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MicroRNA-22 Regulates Hypoxia Signaling in Colon Cancer Cells
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Journal Article
MicroRNA-22 Regulates Hypoxia Signaling in Colon Cancer Cells
2011
Overview
MicroRNAs (MiRNAs) are short, non-coding RNA that regulate a variety of cellular functions by suppressing target protein expression. We hypothesized that a set of microRNA regulate tumor responses to hypoxia by inhibiting components of the hypoxia signaling pathway. We found that miR-22 expression in human colon cancer is lower than in normal colon tissue. We also found that miR-22 controls hypoxia inducible factor 1α (HIF-1α) expression in the HCT116 colon cancer cell line. Over-expression of miR-22 inhibits HIF-1α expression, repressing vascular endothelial growth factor (VEGF) production during hypoxia. Conversely, knockdown of endogenous miR-22 enhances hypoxia induced expression of HIF-1α and VEGF. The conditioned media from cells over-expressing miR-22 contain less VEGF protein than control cells, and also induce less endothelial cell growth and invasion, suggesting miR-22 in adjacent cells influences endothelial cell function. Taken together, our data suggest that miR-22 might have an anti-angiogenic effect in colon cancer.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Biology
/ Cancer
/ Colon
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Humans
/ Hypoxia
/ Hypoxia-Inducible Factor 1, alpha Subunit - genetics
/ Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
/ Medicine
/ MicroRNA
/ miRNA
/ Proteins
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA
/ Signal Transduction - genetics
/ Signal Transduction - physiology
/ Vascular endothelial growth factor
