Potential Targets of Nitidine Chloride in Wilms Tumour Revealed by Network Pharmacology, RNA-Seq and Microarrays

Background: Wilms tumour is the most common childhood renal cancer that requires development of better treatments. Nitidine chloride, a Chinese traditional medicine, could have therapeutic potential for Wilms tumour, however there have been no studies to date. Methods: In-house RNA-seq was performed and public RNA-seq plus microarrays datasets were incorporated for identifying the landscape of differentially expressed genes (DEGs) in Wilms tumour. Meanwhile, the potential targets of nitidine chloride in Wilms tumour were acquired through combined analysis of computational prediction and DEG, which was further validated by molecular docking. The molecular mechanism of nitidine chloride-putative targets was investigated through transcription factors and gene set enrichment analysis. Findings: As a result, a total of 1819 upregulated DEGs and 1942 downregulated DEGs were identified in Wilms tumour. Twenty-three putative targets of nitidine chloride in Wilms tumour were determined and nine showed strong binding force with nitidine chloride in molecular docking. IMPDH2 and MAP4K4 exhibited significant value of prognostic signification. The upregulation of these putative targets in Wilms tumour may be induced by transcription factors (TFs) such as MYC, E2F1, SOX2, MYCN, MITF and CREM. The hub putative targets of nitidine chloride in Wilms tumour were enriched in pathways such as cell cycle, chemokine signaling pathway, glycolysis and gluconeogenesis. Interpretation: In conclusion, the putative pharmacologic targets and molecular pathways of nitidine chloride in Wilms tumour were unveiled in this study. Further research is necessary for confirming the therapeutic effect of nitidine chloride in Wilms tumour. Funding: This work was supported by Natural Science Foundation of Guangxi, China (2018GXNSFAA294025); Guangxi Medical High-level Key Talents Training "139" Program (2020); Guangxi Medical University Training Program for Distinguished Young Scholars ; Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University; Guangxi Degree and Postgraduate Education Reform and Development Research Projects, China (JGY2019050); Innovation Project of Guangxi Graduate Education; Guangxi Zhuang Autonomous Region Health and Family Planning Commission Self-financed Scientific Research Project (Z20200317); Innovation Project of Guangxi Graduate Education (YCSW2021121 Declaration of Interests: The authors have declared no competing interests. Ethics Approval Statement: All patients provided informed consent and approval of this research project was granted by the medical ethics committee of the First Affiliated Hospital of Guangxi Medical University (2020-ky-guoji-135). All experiments involving animals were conducted according to the ethical policies and procedures approved by the ethics committee of the First Affiliated Hospital of Guangxi Medical Univeristy (Approval no. 2020-ky-guoji-135).