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Krüppel样因子信号通路改变与肝细胞癌的潜在靶向治疗

Alterations of Krüppel-like Factor Signaling and Potential Targeted Therapy for Hepatocellular Carcinoma.

作者信息

Fang Rongfei, Sha Chunxiu, Xie Qun, Yao Dengfu, Yao Min

机构信息

Research Center of Clinical Medicine, Department of Medical Immunology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China.

Department of Infectious Diseases, Nantong Haian People's Hospital, Haian 226600, Jiangsu Province, China.

出版信息

Anticancer Agents Med Chem. 2025;25(2):75-85. doi: 10.2174/0118715206301453240910044913.

DOI:10.2174/0118715206301453240910044913
PMID:39313900
Abstract

Krüppel-like factors (KLFs, total 18 members) from the zinc finger protein (ZFP) super-family have a wide range of biological functions in hepatocellular carcinoma (HCC). This paper reviews the recent some progresses of aberrant KLFs with their potential values for diagnosis, prognosis, and targeted therapy in HCC. The recent advances of oncogenic KLFs in the diagnosis, prognosis, and targeted therapy of HCC were reviewed based on the related literature on PUBMED and clinical investigation. Based on the recent literature, KLFs, according to biological functions in HCC, are divided into 4 subgroups: promoting (KLF5, 7, 8, 13), inhibiting (KLF3, 4, 9~12, 14, 17), dual (KLF2, 6), and unknown functions (KLF1, 15, 16, or 18 ?). HCC-related KLFs regulate downstream gene transcription during hepatocyte malignant transformation, participating in cell proliferation, apoptosis, invasion, and metastasis. Some KLFs have diagnostic or prognostic value, and other KLFs with inhibiting promoting function or over-expressing inhibiting roles might be molecular targets for HCC therapy. These data have suggested that Abnormal expressions of KLFs were associated with HCC progression. Among them, some KLFs have revealed the clinical values of diagnosis or prognosis, and other KLFs with the biological functions of promotion or inhibition might be as effectively molecular targets for HCC therapy.

摘要

锌指蛋白(ZFP)超家族中的Krüppel样因子(KLFs,共18个成员)在肝细胞癌(HCC)中具有广泛的生物学功能。本文综述了异常KLFs的近期研究进展及其在HCC诊断、预后和靶向治疗中的潜在价值。基于PUBMED上的相关文献和临床研究,综述了致癌KLFs在HCC诊断、预后和靶向治疗方面的最新进展。根据近期文献,KLFs根据其在HCC中的生物学功能分为4个亚组:促进组(KLF5、7、8、13)、抑制组(KLF3、4、9~12、14、17)、双向组(KLF2、6)和功能未知组(KLF1、15、16或18?)。与HCC相关的KLFs在肝细胞恶性转化过程中调节下游基因转录,参与细胞增殖、凋亡、侵袭和转移。一些KLFs具有诊断或预后价值,而其他具有促进或抑制功能的KLFs可能是HCC治疗的分子靶点。这些数据表明KLFs的异常表达与HCC进展相关。其中,一些KLFs已显示出诊断或预后的临床价值,而其他具有促进或抑制生物学功能的KLFs可能是HCC治疗有效的分子靶点。

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本文引用的文献

1
Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection Exhibited Favorable Survival from Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.乙型肝炎病毒感染的肝细胞癌患者接受免疫检查点抑制剂治疗后生存情况良好:一项系统评价和荟萃分析
Liver Cancer. 2023 Oct 30;13(4):344-354. doi: 10.1159/000534446. eCollection 2024 Aug.
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Preclinical human and murine models of hepatocellular carcinoma (HCC).肝细胞癌(HCC)的临床前人类和鼠模型。
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Racial/Ethnic Disparities and Immunotherapeutic Advances in the Treatment of Hepatocellular Carcinoma.
肝细胞癌治疗中的种族/民族差异与免疫治疗进展
Cancers (Basel). 2024 Jul 3;16(13):2446. doi: 10.3390/cancers16132446.
4
Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies.免疫治疗肝细胞癌的进展:联合治疗的潜力。
Int J Mol Sci. 2024 Jun 21;25(13):6830. doi: 10.3390/ijms25136830.
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Identification of most representative hub-genes for diagnosis, prognosis, and therapies of hepatocellular carcinoma.鉴定用于肝细胞癌诊断、预后和治疗的最具代表性的枢纽基因。
Chin Clin Oncol. 2024 Jun;13(3):32. doi: 10.21037/cco-23-151.
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Novel insights into regulators and functional modulators of adipogenesis.脂肪生成调控因子和功能调节剂的新见解。
Biomed Pharmacother. 2024 Aug;177:117073. doi: 10.1016/j.biopha.2024.117073. Epub 2024 Jul 8.
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Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune-tolerant phase of chronic hepatitis B virus infection: A systematic review and meta-analysis.估算慢性乙型肝炎病毒感染免疫耐受期患者的关键结局和肝细胞癌风险:系统评价和荟萃分析。
Rev Med Virol. 2024 Jul;34(4):e2570. doi: 10.1002/rmv.2570.
8
KLF15-activated MARCH2 boosts cell proliferation and epithelial-mesenchymal transition and presents diagnostic significance for hepatocellular carcinoma.KLF15 激活的 MARCH2 促进细胞增殖和上皮-间充质转化,并对肝细胞癌具有诊断意义。
Exp Cell Res. 2024 Jul 1;440(1):114117. doi: 10.1016/j.yexcr.2024.114117. Epub 2024 Jun 6.
9
Comprehensive analysis of KLF family reveals KLF6 as a promising prognostic and immune biomarker in pancreatic ductal adenocarcinoma.KLF家族的综合分析揭示KLF6是胰腺导管腺癌中有前景的预后和免疫生物标志物。
Cancer Cell Int. 2024 May 21;24(1):177. doi: 10.1186/s12935-024-03369-3.
10
The potential of the nutraceutical berberine in the treatment of hepatocellular carcinoma and other liver diseases such as NAFLD and NASH.营养保健品黄连素在治疗肝细胞癌和其他肝脏疾病(如非酒精性脂肪性肝病和非酒精性脂肪性肝炎)中的潜力。
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