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

被引：16

作者：

Roh, Yun-Gil ^{[1
]}

Mun, Jeong-Yeon ^{[1
]}

Kim, Seon-Kyu ^{[2
,3
]}

Park, Won Young ^{[4
]}

Jeong, Mi-So ^{[1
]}

Kim, Tae Nam ^{[5
]}

Kim, Won-Tae ^{[1
]}

Choi, Yung Hyun ^{[6
]}

Chu, In-Sun ^{[3
,7
]}

Leem, Sun-Hee ^{[1
]}

机构：

[1] Dong A Univ, Dept Biol Sci, Busan 49315, South Korea

[2] Korea Res Inst Biosci & Biotechnol KRIBB, Personalized Genom Med Res Ctr, Daejeon 34141, South Korea

[3] Korea Univ Sci & Technol, KRIBB Sch Biosci, Dept Bioinformat, Daejeon 34113, South Korea

[4] Pusan Natl Univ Hosp, Med Res Inst, Dept Pathol, Busan 49241, South Korea

[5] Pusan Natl Univ Hosp, Med Res Inst, Dept Urol, Busan 49241, South Korea

[6] Dong Eui Univ, Coll Korean Med, Dept Biochem, Busan 47227, South Korea

[7] Korea Res Inst Biosci & Biotechnol KRIBB, Genome Editing Res Ctr, Daejeon 34141, South Korea

来源：

CANCERS | 2020年 / 12卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

bladder cancer; FOXM1; FANCD2; Fanconi anemia pathway; DNA repair; cancer recurrence; TRANSCRIPTION FACTOR FOXM1; FORKHEAD BOX M1; DNA-DAMAGE; MASTER REGULATOR; EXPRESSION; PROGRESSION; APOPTOSIS; CELLS; EPIDEMIOLOGY; GUIDELINES;

D O I：

10.3390/cancers12061417

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1 / 20

页数：19