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1.
Protein & Cell ; (12): 848-866, 2018.
Article Dans Anglais | WPRIM | ID: wpr-758025

Résumé

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.


Sujets)
Animaux , Humains , Souris , Cellules cultivées , Protéines de liaison à l'ADN , Métabolisme , Test de retard de migration électrophorétique , Immunoprécipitation , microARN , Génétique , Métabolisme , Tumeurs , Génétique , Métabolisme
2.
Protein & Cell ; (12): 704-713, 2014.
Article Dans Anglais | WPRIM | ID: wpr-757656

Résumé

Ubiquitin specific protease 33 (USP33) is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multiple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 mediates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robo1 in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer cells. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.


Sujets)
Femelle , Humains , Mâle , Adulte d'âge moyen , Technique de Western , Lignée cellulaire tumorale , Mouvement cellulaire , Génétique , Physiologie , Études de cohortes , Régulation négative , Régulation de l'expression des gènes tumoraux , Cellules HEK293 , Immunohistochimie , Protéines et peptides de signalisation intercellulaire , Métabolisme , Estimation de Kaplan-Meier , Tumeurs du poumon , Génétique , Métabolisme , Anatomopathologie , Protéines de tissu nerveux , Métabolisme , Pronostic , Interférence par ARN , Récepteurs immunologiques , Métabolisme , RT-PCR , Transduction du signal , Génétique , Physiologie , Ubiquitin thiolesterase , Génétique , Métabolisme
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