TRIM24/ZFX affects the stemness and resistance to 5-FU of colorectal cancer cells.

IF 1.9 4区 医学 Q3 INFECTIOUS DISEASES Journal of Chemotherapy Pub Date : 2024-09-02 DOI:10.1080/1120009X.2024.2376422
Xuming Yao, Zhiping Yang, Guoxin Hou, Jialu Jiang, Lvbin Wang, Jin Jiang
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Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death, and about 10% of all malignancies are CRC. Cancer stem cells are considered main culprits in CRC treatment resistance and disease recurrence. This study explored the effects of tripartite motif containing 24 (TRIM24) and zinc finger protein, X-linked (ZFX) on CRC cell stemness and 5-FU resistance. A 5-FU-resistant cell line (HT29-5-FU) was constructed for functional analysis of CRC 5-FU-resistant cells. qRT-PCR and western blot (WB) were employed to analyze mRNA and protein levels of ZFX in 5-FU resistant cells and sensitive cells. WB was also utilized to analyze the surface markers of stem cells in each group. CCK-8 assay determined the IC50 values of different cell groups treated with 5-FU. The sphere-forming ability of cells in each group was determined using tumor sphere assay. Dual-luciferase reporter gene assay validated binding of ZFX to TRIM24. ZFX was highly expressed in HT29-5-FU cells. Silencing ZFX significantly reduced the 5-FU resistance and IC50 value of HT29-5-FU cells, and the surface markers and cell sphere-forming ability of stem cells were also significantly reduced. The function of HT29 cells was opposite when ZFX was overexpressed. In CRC cells, TRIM24 was an upstream transcription factor of ZFX, and they interacted with each other. TRIM24 activated the expression of ZFX to influence the stemness and 5-FU resistance of cells. The TRIM24/ZFX regulatory axis affected the stemness of CRC cells and their sensitivity to 5-FU, providing potential drug targets for novel therapeutic avenues for CRC.

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TRIM24/ZFX影响结直肠癌细胞的干性和对5-FU的耐药性。
结肠直肠癌(CRC)是导致癌症死亡的第二大原因,约有10%的恶性肿瘤是CRC。癌症干细胞被认为是导致 CRC 耐药性和疾病复发的罪魁祸首。本研究探讨了含三方基序24(TRIM24)和锌指蛋白X连锁(ZFX)对CRC细胞干性和5-FU耐药性的影响。为了对 CRC 5-FU 耐药细胞进行功能分析,研究人员构建了一个 5-FU 耐药细胞系(HT29-5-FU),并采用 qRT-PCR 和 Western blot (WB) 技术分析 5-FU 耐药细胞和敏感细胞中 ZFX 的 mRNA 和蛋白水平。还利用WB分析了各组干细胞的表面标记物。CCK-8试验测定了不同细胞组在5-FU处理下的IC50值。肿瘤球试验测定了各组细胞的成球能力。双荧光素酶报告基因检测验证了ZFX与TRIM24的结合。ZFX在HT29-5-FU细胞中高表达。沉默ZFX能明显降低HT29-5-FU细胞对5-FU的耐药性和IC50值,干细胞的表面标志物和细胞球形成能力也明显降低。当ZFX过表达时,HT29细胞的功能则相反。在 CRC 细胞中,TRIM24 是 ZFX 的上游转录因子,它们之间存在相互作用。TRIM24激活ZFX的表达,从而影响细胞的干性和对5-FU的耐受性。TRIM24/ZFX调控轴影响了CRC细胞的干性及其对5-FU的敏感性,为CRC的新型治疗途径提供了潜在的药物靶点。
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来源期刊
Journal of Chemotherapy
Journal of Chemotherapy 医学-药学
CiteScore
3.70
自引率
0.00%
发文量
144
审稿时长
6-12 weeks
期刊介绍: The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.
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