B7-H3-mediated deubiquitination stabilizing CYP1B1 expression promotes chemotherapy resistance in colorectal cancer

被引：0
作者：
Liu, Huan [2 ]
Li, Guifang [2 ]
Shen, Chenjie [2 ]
Qi, Xiaowei [4 ]
Liu, Yankui [4 ]
Hua, Dong [5 ]
Mao, Yong [2 ]
Zhang, Ting [1 ,3 ]
机构：
[1] Jiangnan Univ, Affiliated Hosp, Inst Canc, Wuxi 214062, Jiangsu, Peoples R China
[2] Jiangnan Univ, Affiliated Hosp, Dept Oncol, Wuxi 214062, Jiangsu, Peoples R China
[3] Univ Plymouth, Fac Hlth, Peninsula Med Sch, Plymouth PL6 8BU, Devon, England
[4] Jiangnan Univ, Dept Pathol, Affiliated Hosp, Wuxi 214062, Jiangsu, Peoples R China
[5] Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Wuxi, Peoples R China
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2025年 / 1871卷 / 05期
关键词：
CRC; B7-H3; Chemotherapy resistance; Ubiquitination; B7-H3; PROMOTES; CELLS; METABOLISM; MECHANISM;
D O I：
10.1016/j.bbadis.2025.167771
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. It is frequently characterized by chemotherapy resistance,which is a predominant factor contributing to unfavorable patient prognosis. B7-H3 is a novel tumor marker and a potential immunotherapy target. High B7-H3 expression in colorectal cancer is associated with adverse prognosis. In this study, we noted increased B7-H3 expression in colorectal cancer tumor tissues. Both in vivo and in vitro experiments demonstrated that increased B7-H3 expression promotes resistance to chemotherapy in CRC. Furthermore, our findings suggest that B7-H3 mediates CRC resistance by modulating CYP1B1 expression. Mechanistic investigations indicated that B7-H3 inhibited the ubiquitination of CYP1B1, stabilized its expression,and consequently enhanced chemotherapeutic resistance in CRC. In summary, our results underscore the significance of the B7-H3-CYP1B1 interaction as a crucial therapeutic target for overcoming chemotherapy resistance in CRC.
引用
收藏
页数：12
相关论文
共 37 条
  • [31] Dallas N.A., Xia L., Fan F., Gray M.J., Et al., Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition, Cancer Res., 69, 5, pp. 1951-1957, (2009)
  • [32] Hu T., Li Z., Gao C.Y., Cho C.H., Mechanisms of drug resistance in colon cancer and its therapeutic strategies, World J. Gastroenterol., 22, 30, pp. 6876-6889, (2016)
  • [33] Mortezaee K., B7-H3 immunoregulatory roles in cancer, Biomed. Pharmacother., 163, (2023)
  • [34] Mahmoud A.M., Frank I., Orme J.J., Lavoie R.R., Et al., Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer, BMC Urol., 22, 1, (2022)
  • [35] Ma Y., Zhan S., Lu H., Wang R., Et al., B7-H3 regulates KIF15-activated ERK1/2 pathway and contributes to radioresistance in colorectal cancer, Cell Death Dis., 11, 10, (2020)
  • [36] McFadyen M.C., McLeod H.L., Jackson F.C., Melvin W.T., Doehmer J., Murray G.I., Cytochrome P450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance, Biochem. Pharmacol., 62, 2, pp. 207-212, (2001)
  • [37] Mu W., Hu C., Zhang H., Qu Z., Et al., miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression, Cell Res., 25, 4, pp. 477-495, (2015)
1234