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已发表论文
维生素 C 通过抑制 HIF-1 通路选择性地抑制肾透明细胞癌细胞的生长
Authors Wang C, Zhou Y, Liang Y, Pan J, Qiao J, Chen L, Liu S, Chen J, Wang J , Sun X, Ma J , Cai M
Received 14 January 2025
Accepted for publication 30 August 2025
Published 20 September 2025 Volume 2025:18 Pages 1069—1081
DOI https://doi.org/10.2147/OTT.S512698
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Tohru Yamada
Che Wang,1,2 Yaoyang Zhou,1 Yu Liang,1 Jue Pan,1 Jinyu Qiao,1 Lingbo Chen,1 Silin Liu,1 Jie Chen,1 Jin Wang,1 Xiao Sun,1 Jinlu Ma,1 Mengjiao Cai1
1Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Medical and Pharmaceutical Informatics, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China
Correspondence: Jinlu Ma, Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Email majinlu@xjtufh.edu.cn Mengjiao Cai, Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Email caimengjiao@xjtu.edu.cn
Aim: To observe the effect of vitamin C on Kidney renal clear cell carcinoma (KIRC) and investigate its mechanism.
Methods and Results: Firstly, 29 vitamin C direct target proteins (DPTs) were identified by Drug Bank 5.0, and the protein-protein interaction (PPI) network and signaling pathways of vitamin C DPTs were analyzed. The results showed that vitamin C was not only related to KIRC, but also to the HIF-1 pathway. Meanwhile, the top 300 highly expressed genes of KIRC were obtained by GEPIA. Next, We compared the genes of four vitamin C targets in the PPI network with highly expressed genes in KIRC. Interestingly, these common genes are also involved in HIF-1 pathway. Additionally, we utilized RNA-Seq technology to explore the differentially expressed genes in KIRC with vitamin C compared to those not intervened. We observed that these differentially expressed genes exhibited a close association with hypoxia. Finally, we observed the inhibitory effect of Vitamin C on KIRC by Cell Counting Kit-8 (CCK8) assay, real-time quantitative PCR, Western blotting, flow cytometry, and colony formation assay, and confirmed that Vitamin C inhibits the growth of KIRC cells through the HIF-1 pathway.
Conclusion: Through bioinformatics analyses, we identified the molecular mechanism of vitamin C’s role in KIRC and verified it through a series of experiments. Combined bioinformatics analysis will play an important role in future drug-disease interaction studies.
Keywords: vitamin C, kidney renal clear cell carcinoma, HIF-1 signaling pathway, therapeutic target genes, integrated bioinformatical analysis
1Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Medical and Pharmaceutical Informatics, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China
Correspondence: Jinlu Ma, Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Email majinlu@xjtufh.edu.cn Mengjiao Cai, Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Email caimengjiao@xjtu.edu.cn
Aim: To observe the effect of vitamin C on Kidney renal clear cell carcinoma (KIRC) and investigate its mechanism.
Methods and Results: Firstly, 29 vitamin C direct target proteins (DPTs) were identified by Drug Bank 5.0, and the protein-protein interaction (PPI) network and signaling pathways of vitamin C DPTs were analyzed. The results showed that vitamin C was not only related to KIRC, but also to the HIF-1 pathway. Meanwhile, the top 300 highly expressed genes of KIRC were obtained by GEPIA. Next, We compared the genes of four vitamin C targets in the PPI network with highly expressed genes in KIRC. Interestingly, these common genes are also involved in HIF-1 pathway. Additionally, we utilized RNA-Seq technology to explore the differentially expressed genes in KIRC with vitamin C compared to those not intervened. We observed that these differentially expressed genes exhibited a close association with hypoxia. Finally, we observed the inhibitory effect of Vitamin C on KIRC by Cell Counting Kit-8 (CCK8) assay, real-time quantitative PCR, Western blotting, flow cytometry, and colony formation assay, and confirmed that Vitamin C inhibits the growth of KIRC cells through the HIF-1 pathway.
Conclusion: Through bioinformatics analyses, we identified the molecular mechanism of vitamin C’s role in KIRC and verified it through a series of experiments. Combined bioinformatics analysis will play an important role in future drug-disease interaction studies.
Keywords: vitamin C, kidney renal clear cell carcinoma, HIF-1 signaling pathway, therapeutic target genes, integrated bioinformatical analysis