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Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance

Although the 5-year survival rate of patients diagnosed with nonmuscle invasive bladder cancer (NMIBC) has reached 85%, more than 50% of patients suffer from frequent recurrences. To identify molecular targets associated with recurrence of NMIBC, we analyzed gene expression data and found that FOXM1...

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Autores principales: Roh, Yun-Gil, Mun, Jeong-Yeon, Kim, Seon-Kyu, Park, Won Young, Jeong, Mi-So, Kim, Tae Nam, Kim, Won-Tae, Choi, Yung Hyun, Chu, In-Sun, Leem, Sun-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352315/
https://www.ncbi.nlm.nih.gov/pubmed/32486251
http://dx.doi.org/10.3390/cancers12061417
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author Roh, Yun-Gil
Mun, Jeong-Yeon
Kim, Seon-Kyu
Park, Won Young
Jeong, Mi-So
Kim, Tae Nam
Kim, Won-Tae
Choi, Yung Hyun
Chu, In-Sun
Leem, Sun-Hee
author_facet Roh, Yun-Gil
Mun, Jeong-Yeon
Kim, Seon-Kyu
Park, Won Young
Jeong, Mi-So
Kim, Tae Nam
Kim, Won-Tae
Choi, Yung Hyun
Chu, In-Sun
Leem, Sun-Hee
author_sort Roh, Yun-Gil
collection PubMed
description Although the 5-year survival rate of patients diagnosed with nonmuscle invasive bladder cancer (NMIBC) has reached 85%, more than 50% of patients suffer from frequent recurrences. To identify molecular targets associated with recurrence of NMIBC, we analyzed gene expression data and found that FOXM1 and FANCD2 were involved in recurrence. Therefore, we investigated how these genes were involved in the mechanism of recurrence and confirmed their usefulness as biomarkers. Investigation have shown that FOXM1 directly regulated the transcription of FANCD2, which is the key gene of the Fanconi anemia (FA) pathway. Depletion of FOXM1 resulted in DNA repair defects in the FA pathway and in decreased resistance to chemotherapy. Thus, the FANCD2-associated FA pathway activated by FOXM1 is an important mechanism involved in chemotherapy-related recurrence. In conclusion, FOXM1 and FANCD2 can be used as prognostic factors that are associated with high risk of recurrence and with anticancer drug resistance properties in NMIBC patients.
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spelling pubmed-73523152020-07-21 Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance Roh, Yun-Gil Mun, Jeong-Yeon Kim, Seon-Kyu Park, Won Young Jeong, Mi-So Kim, Tae Nam Kim, Won-Tae Choi, Yung Hyun Chu, In-Sun Leem, Sun-Hee Cancers (Basel) Article Although the 5-year survival rate of patients diagnosed with nonmuscle invasive bladder cancer (NMIBC) has reached 85%, more than 50% of patients suffer from frequent recurrences. To identify molecular targets associated with recurrence of NMIBC, we analyzed gene expression data and found that FOXM1 and FANCD2 were involved in recurrence. Therefore, we investigated how these genes were involved in the mechanism of recurrence and confirmed their usefulness as biomarkers. Investigation have shown that FOXM1 directly regulated the transcription of FANCD2, which is the key gene of the Fanconi anemia (FA) pathway. Depletion of FOXM1 resulted in DNA repair defects in the FA pathway and in decreased resistance to chemotherapy. Thus, the FANCD2-associated FA pathway activated by FOXM1 is an important mechanism involved in chemotherapy-related recurrence. In conclusion, FOXM1 and FANCD2 can be used as prognostic factors that are associated with high risk of recurrence and with anticancer drug resistance properties in NMIBC patients. MDPI 2020-05-30 /pmc/articles/PMC7352315/ /pubmed/32486251 http://dx.doi.org/10.3390/cancers12061417 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roh, Yun-Gil
Mun, Jeong-Yeon
Kim, Seon-Kyu
Park, Won Young
Jeong, Mi-So
Kim, Tae Nam
Kim, Won-Tae
Choi, Yung Hyun
Chu, In-Sun
Leem, Sun-Hee
Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance
title Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance
title_full Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance
title_fullStr Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance
title_full_unstemmed Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance
title_short Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance
title_sort fanconi anemia pathway activation by foxm1 is critical to bladder cancer recurrence and anticancer drug resistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352315/
https://www.ncbi.nlm.nih.gov/pubmed/32486251
http://dx.doi.org/10.3390/cancers12061417
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