TDP-43 regulates cancer-associated microRNAs
Protein & Cell
; (12): 848-866, 2018.
Article
em En
| WPRIM
| ID: wpr-758025
Biblioteca responsável:
WPRO
ABSTRACT
Aberrant regulation of miRNA genes contributes to pathogenesis of a wide range of human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a RNA/DNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs regulated by TDP-43 using RNA-Seq coupled with an siRNA-mediated knockdown approach. TDP-43 knockdown affected the expression of a number of miRNAs. In addition, TDP-43 down-regulation led to alterations in the patterns of different isoforms of miRNAs (isomiRs) and miRNA arm selection, suggesting a previously unknown role of TDP-43 in miRNA processing. A number of TDP-43 associated miRNAs, and their candidate target genes, are associated with human cancers. Our data reveal highly complex roles of TDP-43 in regulating different miRNAs and their target genes. Our results suggest that TDP-43 may promote migration of lung cancer cells by regulating miR-423-3p. In contrast, TDP-43 increases miR-500a-3p expression and binds to the mature miR-500a-3p sequence. Reduced expression of miR-500a-3p is associated with poor survival of lung cancer patients, suggesting that TDP-43 may have a suppressive role in cancer by regulating miR-500a-3p. Cancer-associated genes LIF and PAPPA are possible targets of miR-500a-3p. Our work suggests that TDP-43-regulated miRNAs may play multifaceted roles in the pathogenesis of cancer.
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Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Células Cultivadas
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Ensaio de Desvio de Mobilidade Eletroforética
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MicroRNAs
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Imunoprecipitação
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Proteínas de Ligação a DNA
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Genética
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Metabolismo
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Protein & Cell
Ano de publicação:
2018
Tipo de documento:
Article