Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance
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 t...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84353-9 |
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| author | Hongxin HE Shiyao ZHENG Shangkun JIN Weijie HUANG Enhao WEI Shen GUAN Chunkang YANG |
| author_facet | Hongxin HE Shiyao ZHENG Shangkun JIN Weijie HUANG Enhao WEI Shen GUAN Chunkang YANG |
| author_sort | Hongxin HE |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fff2464a3d8a44348ae6374348d3c4d4 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-fff2464a3d8a44348ae6374348d3c4d42025-01-05T12:18:47ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-024-84353-9Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistanceHongxin HE0Shiyao ZHENG1Shangkun JIN2Weijie HUANG3Enhao WEI4Shen GUAN5Chunkang YANG6Department of Colorectal Surgery, Clinical Oncology School of Fujian Medical UniversityDepartment of Colorectal Surgery, Clinical Oncology School of Fujian Medical UniversityDepartment of Colorectal Surgery, Clinical Oncology School of Fujian Medical UniversityFujian Medical University Union HospitalDepartment of Colorectal Surgery, Clinical Oncology School of Fujian Medical UniversityDepartment of Colorectal Surgery, Clinical Oncology School of Fujian Medical UniversityDepartment of Colorectal Surgery, Clinical Oncology School of Fujian Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-024-84353-9Colon cancerNucleotide metabolism5-fluorouracil resistanceNDUFA4L2Prognosis |
| spellingShingle | Hongxin HE Shiyao ZHENG Shangkun JIN Weijie HUANG Enhao WEI Shen GUAN Chunkang YANG Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance Scientific Reports Colon cancer Nucleotide metabolism 5-fluorouracil resistance NDUFA4L2 Prognosis |
| title | Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance |
| title_full | Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance |
| title_fullStr | Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance |
| title_full_unstemmed | Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance |
| title_short | Nucleotide metabolism-associated drug resistance gene NDUFA4L2 promotes colon cancer progression and 5-FU resistance |
| title_sort | nucleotide metabolism associated drug resistance gene ndufa4l2 promotes colon cancer progression and 5 fu resistance |
| topic | Colon cancer Nucleotide metabolism 5-fluorouracil resistance NDUFA4L2 Prognosis |
| url | https://doi.org/10.1038/s41598-024-84353-9 |
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