MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.
The miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in...
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doaj-1d495769a6624bbd88c19afc5e8ffd072020-11-25T02:06:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8062510.1371/journal.pone.0080625MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells.Dan ChenZujian ChenYi JinDragan DragasLeitao ZhangBarima S AdjeiAnxun WangYang DaiXiaofeng ZhouThe miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in adult tissues, such as dermal wound healing, and a number of disease processes, including cancer. By combining 5 independent genome-wide expression profiling experiments, we identified a panel of 266 unique transcripts that were down-regulated in epithelial cells transfected with miR-99 family members. A comprehensive bioinformatics analysis using 12 different sequence-based microRNA target prediction algorithms revealed that 81 out of these 266 down-regulated transcripts are potential direct targets for the miR-99 family. Confirmation experiments and functional analyses were performed to further assess 6 selected miR-99 target genes, including mammalian Target of rapamycin (mTOR), Homeobox A1 (HOXA1), CTD small phosphatase-like (CTDSPL), N-myristoyltransferase 1 (NMT1), Transmembrane protein 30A (TMEM30A), and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5). HOXA1 is a known proto-oncogene, and it also plays an important role in embryonic development. The direct targeting of the miR-99 family to two candidate binding sequences located in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a ribonucleoprotein-immunoprecipitation (RIP-IP) assay. Ectopic transfection of miR-99 family reduced the expression of HOXA1, which, in consequence, down-regulated the expression of its downstream gene (i.e., Bcl-2) and led to reduced proliferation and cell migration, as well as enhanced apoptosis. In summary, we identified a number of high-confidence miR-99 family target genes, including proto-oncogene HOXA1, which may play an important role in regulating epithelial cell proliferation and migration during physiological disease processes, such as dermal wound healing and tumorigenesis.http://europepmc.org/articles/PMC3849180?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dan Chen Zujian Chen Yi Jin Dragan Dragas Leitao Zhang Barima S Adjei Anxun Wang Yang Dai Xiaofeng Zhou |
spellingShingle |
Dan Chen Zujian Chen Yi Jin Dragan Dragas Leitao Zhang Barima S Adjei Anxun Wang Yang Dai Xiaofeng Zhou MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. PLoS ONE |
author_facet |
Dan Chen Zujian Chen Yi Jin Dragan Dragas Leitao Zhang Barima S Adjei Anxun Wang Yang Dai Xiaofeng Zhou |
author_sort |
Dan Chen |
title |
MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. |
title_short |
MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. |
title_full |
MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. |
title_fullStr |
MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. |
title_full_unstemmed |
MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. |
title_sort |
microrna-99 family members suppress homeobox a1 expression in epithelial cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
The miR-99 family is one of the evolutionarily most ancient microRNA families, and it plays a critical role in developmental timing and the maintenance of tissue identity. Recent studies, including reports from our group, suggested that the miR-99 family regulates various physiological processes in adult tissues, such as dermal wound healing, and a number of disease processes, including cancer. By combining 5 independent genome-wide expression profiling experiments, we identified a panel of 266 unique transcripts that were down-regulated in epithelial cells transfected with miR-99 family members. A comprehensive bioinformatics analysis using 12 different sequence-based microRNA target prediction algorithms revealed that 81 out of these 266 down-regulated transcripts are potential direct targets for the miR-99 family. Confirmation experiments and functional analyses were performed to further assess 6 selected miR-99 target genes, including mammalian Target of rapamycin (mTOR), Homeobox A1 (HOXA1), CTD small phosphatase-like (CTDSPL), N-myristoyltransferase 1 (NMT1), Transmembrane protein 30A (TMEM30A), and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5). HOXA1 is a known proto-oncogene, and it also plays an important role in embryonic development. The direct targeting of the miR-99 family to two candidate binding sequences located in the HOXA1 mRNA was confirmed using a luciferase reporter gene assay and a ribonucleoprotein-immunoprecipitation (RIP-IP) assay. Ectopic transfection of miR-99 family reduced the expression of HOXA1, which, in consequence, down-regulated the expression of its downstream gene (i.e., Bcl-2) and led to reduced proliferation and cell migration, as well as enhanced apoptosis. In summary, we identified a number of high-confidence miR-99 family target genes, including proto-oncogene HOXA1, which may play an important role in regulating epithelial cell proliferation and migration during physiological disease processes, such as dermal wound healing and tumorigenesis. |
url |
http://europepmc.org/articles/PMC3849180?pdf=render |
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