Farooq Umar, Li Jun, Chang Zhijie
Jinfeng Laboratory, No. 313 Jinyue Road, High-Tech Zone, Chongqing 401329, China.
State Key Laboratory of Membrane Biology, School of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China .
Cancers (Basel). 2025 Jul 19;17(14):2401. doi: 10.3390/cancers17142401.
The transcriptional co-factor cell-cycle-related and expression-elevated protein in tumors (CREPT) has emerged as a critical driver of the cell cycle and a significant contributor to tumorigenesis. The aberrant expression or upregulation of CREPT boosts multiple signaling pathways, including Wnt/β-catenin, STAT3 and NF-κB/TNFR2, which are frequently dysregulated in various cancers and are associated with poor overall survival. In preclinical studies, CREPT knockdown via shRNA has demonstrated sustained tumor growth regression. Recent researches have uncovered additional functions of CREPT, including roles in metabolic regulation, tissue repair, and microenvironmental remodeling, further establishing it as a pleiotropic transcriptional regulator. Currently, there is no therapeutic agent that directly inhibits CREPT expression in clinic. However, miRNAs and other methods have been used to target CREPT, which have yielded useful results in inhibiting tumor growth. In this review, we discuss the role of CREPT in the hallmarks of cancer and propose that targeting CREPT will reverse tumor growth and may improve the immune checkpoint inhibitors in combination in CREPT-driven cancers.
转录辅因子肿瘤细胞周期相关且表达上调蛋白(CREPT)已成为细胞周期的关键驱动因子和肿瘤发生的重要促成因素。CREPT的异常表达或上调会增强多种信号通路,包括Wnt/β-连环蛋白、STAT3和NF-κB/TNFR2,这些信号通路在各种癌症中经常失调,并与总体生存率低相关。在临床前研究中,通过短发夹RNA(shRNA)敲低CREPT已证明肿瘤生长持续消退。最近的研究发现了CREPT的其他功能,包括在代谢调节、组织修复和微环境重塑中的作用,进一步确立了它作为一种多效性转录调节因子的地位。目前,临床上尚无直接抑制CREPT表达的治疗药物。然而,微小RNA(miRNA)和其他方法已被用于靶向CREPT,在抑制肿瘤生长方面取得了有益的结果。在本综述中,我们讨论了CREPT在癌症特征中的作用,并提出靶向CREPT将逆转肿瘤生长,且可能改善CREPT驱动型癌症中联合使用的免疫检查点抑制剂的疗效。