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核苷酸代谢相关耐药基因NDUFA4L2促进结肠癌进展及5-氟尿嘧啶耐药。

Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance.

作者信息

He Hongxin, Zheng Shiyao, Jin Shangkun, Huang Weijie, Wei Enhao, Guan Shen, Yang Chunkang

机构信息

Department of Colorectal Surgery, Clinical Oncology School of Fujian Medical University, Fuzhou, 350004, Fujian, Fujian, P.R. China.

Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, China.

出版信息

Sci Rep. 2025 Jan 2;15(1):570. doi: 10.1038/s41598-024-84353-9.

DOI:10.1038/s41598-024-84353-9
PMID:39747340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11695588/
Abstract

Chemotherapy is an effective way to improve the prognosis of colorectal cancer patients, but patient resistance to chemotherapeutic agents is becoming a major obstacle to treatment. Nucleotide metabolism correlates with the progression of colorectal cancer and chemotherapy resistance, but the mechanisms involved need to be further investigated. We calculated the half-maximal inhibitory concentrations (IC50) of 5-Fluorouracil (5-FU) in colorectal cancer patients using the "oncopredict" package, screened nucleotide metabolism-related drug resistance genes, and constructed a risk score model. According to the Kaplan-Meier(KM) analysis, the overall survival (OS) and disease-free survival (PFS) of the high-risk group were significantly lower than those of the low-risk group. In addition, the nomogram we constructed had good performance in predicting OS in colon adenocarcinoma (COAD) patients. We validated NDUFA4L2 by cellular functionality experiments, animal tumorigenesis experiments and drug resistance experiments. It was demonstrated that NDUFA4L2 promoted the proliferation and migration of colon cancer cells, while the abnormal regulation of NDUFA4L2 affected the 5-FU resistance of colon cancer cells. In conclusion, we found that NDUFA4L2 promotes the progression and metastasis of colon cancer, as well as resistance to 5-FU chemotherapy.

摘要

化疗是改善结直肠癌患者预后的有效方法，但患者对化疗药物的耐药性正成为治疗的主要障碍。核苷酸代谢与结直肠癌的进展和化疗耐药性相关，但其涉及的机制仍需进一步研究。我们使用“oncopredict”软件包计算了结直肠癌患者中5-氟尿嘧啶（5-FU）的半数抑制浓度（IC50），筛选了核苷酸代谢相关的耐药基因，并构建了风险评分模型。根据Kaplan-Meier（KM）分析，高危组的总生存期（OS）和无病生存期（PFS）显著低于低危组。此外，我们构建的列线图在预测结肠腺癌（COAD）患者的OS方面具有良好的性能。我们通过细胞功能实验、动物肿瘤发生实验和耐药实验对NDUFA4L2进行了验证。结果表明，NDUFA4L2促进结肠癌细胞的增殖和迁移，而NDUFA4L2的异常调节影响结肠癌细胞对5-FU的耐药性。总之，我们发现NDUFA4L2促进结肠癌的进展和转移，以及对5-FU化疗的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/749c53b19958/41598_2024_84353_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/8571e0bbaed3/41598_2024_84353_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/749c53b19958/41598_2024_84353_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/8571e0bbaed3/41598_2024_84353_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/bbf5fde987c1/41598_2024_84353_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/e7c27b4715e5/41598_2024_84353_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/3b79ba70df99/41598_2024_84353_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11695588/749c53b19958/41598_2024_84353_Fig7_HTML.jpg

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本文引用的文献

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LncRNA GAS6-AS1 contributes to 5-fluorouracil resistance in colorectal cancer by facilitating the binding of PCBP1 with MCM3.长链非编码 RNA GAS6-AS1 通过促进 PCBP1 与 MCM3 的结合促进结直肠癌对 5-氟尿嘧啶的耐药性。
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Elevated of NDUFA4L2 expression in colon adenocarcinoma is correlated with an unfavorable prognosis and increased immune cell infiltration.结肠腺癌中NDUFA4L2表达升高与不良预后及免疫细胞浸润增加相关。
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