KIAA1549 promotes the development and chemoresistance of colorectal cancer by upregulating ERCC2

被引:1
作者
Ye, Feng [1 ]
Xie, Yuwen [1 ]
Lin, Mingdao [2 ,3 ]
Liu, Yang [1 ]
Fang, Yuan [1 ]
Chen, Keli [4 ]
Zhang, Yaowei [1 ]
Ding, Yi [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Radiat Oncol, Guangzhou 510515, Peoples R China
[2] Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Dept Gen Surg, Guangzhou 510515, Peoples R China
[3] Southern Med Univ, Nanfang Hosp, Sch Clin Med 1, Guangdong Prov Key Lab Precis Med Gastrointestinal, Guangzhou 510515, Peoples R China
[4] Southern Med Univ, Nanfang Hosp, Huiqiao Med Ctr, Guangzhou 510515, Peoples R China
基金
中国国家自然科学基金;
关键词
Colorectal cancer; KIAA1549; Development; Chemotherapy; Chemoresistance; NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA LEVELS; FUSION GENE; PHASE-II; CISPLATIN; DNA; PATHWAY; POLYMORPHISMS; FLUOROURACIL; CHEMOTHERAPY;
D O I
10.1007/s11010-023-04751-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Chemotherapy is the mainstay of treatment for patients with CRC in II-IV stages. Resistance to chemotherapy occurs commonly, which results in treatment failure. Therefore, the identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and developing new therapeutic strategies. Herein, we assessed the roles of KIAA1549 in promoting tumor development and chemoresistance in colorectal cancer. As a result, we found that KIAA1549 expression is up-regulation in CRC. Public databases revealed a progressive up-regulation of KIAA1549 expression from adenomas to carcinomas. Functional characterization uncovered that KIAA1549 promotes tumor malignant phenotypes and boosts the chemoresistance of CRC cells in an ERCC2-dependent manner. Inhibition of KIAA1549 and ERCC2 effectively enhanced the sensitivity to chemotherapeutic drugs oxaliplatin and 5-fluorouracil. Our findings suggest that endogenous KIAA1549 might function as a tumor development-promoting role and trigger chemoresistance in colorectal cancer partly by upregulating DNA repair protein ERCC2. Hence, KIAA1549 could be an effective therapeutic target for CRC and inhibition of KIAA1549 combined with chemotherapy might be a potential therapeutic strategy in the future.
引用
收藏
页码:629 / 642
页数:14
相关论文
共 35 条
[21]   Identification of clinical trait-related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer [J].
Li, Na ;
Zhan, Xianquan .
EPMA JOURNAL, 2019, 10 (03) :273-290
[22]   ERCC2 Helicase Domain Mutations Confer Nucleotide Excision Repair Deficiency and Drive Cisplatin Sensitivity in Muscle-Invasive Bladder Cancer [J].
Li, Qiang ;
Damish, Alexis W. ;
Frazier, Zoe ;
Liu, David ;
Reznichenko, Elizaveta ;
Kamburov, Atanas ;
Bell, Andrew ;
Zhao, Huiyong ;
Jordan, Emmet J. ;
Gao, S. Paul ;
Ma, Jennifer ;
Abbosh, Philip H. ;
Bellmunt, Joaquim ;
Plimack, Elizabeth R. ;
Lazaro, Jean-Bernard ;
Solit, David B. ;
Bajorin, Dean ;
Rosenberg, Jonathan E. ;
D'Andrea, Alan D. ;
Riaz, Nadeem ;
Van Allen, Eliezer M. ;
Iyer, Gopa ;
Mouw, Kent W. .
CLINICAL CANCER RESEARCH, 2019, 25 (03) :977-988
[23]   S100P contributes to promoter demethylation and transcriptional activation of SLC2A5 to promote metastasis in colorectal cancer [J].
Lin, Mingdao ;
Fang, Yuan ;
Li, Zhenkang ;
Li, Yongsheng ;
Feng, Xiaochuang ;
Zhan, Yizhi ;
Xie, Yuwen ;
Liu, Yuechen ;
Liu, Zehao ;
Li, Guoxin ;
Shen, Zhiyong ;
Deng, Haijun .
BRITISH JOURNAL OF CANCER, 2021, 125 (05) :734-747
[24]   Resistance to chemotherapy in cancer: A complex and integrated cellular response [J].
Mellor, Howard R. ;
Callaghan, Richard .
PHARMACOLOGY, 2008, 81 (04) :275-300
[25]   ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy [J].
Metzger, R ;
Leichman, CG ;
Danenberg, KD ;
Danenberg, PV ;
Lenz, HJ ;
Hayashi, K ;
Groshen, S ;
Salonga, D ;
Cohen, H ;
Laine, L ;
Crookes, P ;
Silberman, H ;
Baranda, J ;
Konda, K ;
Leichman, L .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (01) :309-316
[26]  
Nagase T, 2000, DNA RES, V7, P273
[27]   The role of DNA repair pathways in cisplatin resistant lung cancer [J].
O'Grady, Shane ;
Finn, Stephen P. ;
Cuffe, Sinead ;
Richard, Derek J. ;
O'Byrne, Kenneth J. ;
Barr, Martin P. .
CANCER TREATMENT REVIEWS, 2014, 40 (10) :1161-1170
[28]   A Novel Cell-Penetrating Antibody Fragment Inhibits the DNA Repair Protein RAD51 [J].
Pastushok, Landon ;
Fu, Yongpeng ;
Lin, Leo ;
Luo, Yu ;
DeCoteau, John F. ;
Lee, Ken ;
Geyer, C. Ronald .
SCIENTIFIC REPORTS, 2019, 9 (1) :11227
[29]   Increasing Incidence of Early-Onset Colorectal Cancer [J].
Sinicrope, Frank A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2022, 386 (16) :1547-1558
[30]   Targeted therapy by combined inhibition of the RAF and mTOR kinases in malignant spindle cell neoplasm harboring the KIAA1549-BRAF fusion protein [J].
Subbiah, Vivek ;
Westin, Shannon N. ;
Wang, Kai ;
Araujo, Dejka ;
Wang, Wei-Lien ;
Miller, Vincent A. ;
Ross, Jeffrey S. ;
Stephens, Phillip J. ;
Palmer, Gary A. ;
Ali, Siraj M. .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2014, 7