Research Paper Volume 16, Issue 4 pp 3363—3385
Pan-cancer analysis of NUDT21 and its effect on the proliferation of human head and neck squamous cell carcinoma
- 1 Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- 2 Department of Otolaryngology Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130000, China
- 3 College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- 4 Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- 5 Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Received: November 1, 2023 Accepted: January 8, 2024 Published: February 12, 2024
https://doi.org/10.18632/aging.205539How to Cite
Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Based on bioinformatics research of NUDT21 in pan-cancer, we aimed to clarify the mechanism of NUDT21 in HHNC by experiment.
Methods: The correlation between differential expression of NUDT21 in pan-cancer and survival prognosis, genomic instability, tumor stemness, DNA repair, RNA methylation and with immune microenvironment were analyzed by the application of different pan-cancer analysis web databases. In addition, immunohistochemistry staining and genetic detection of NUDT21 in HHNCC tumor tissues by immunohistochemistry and qRT-PCR. Then, through in vitro cell experiments, NUDT21 was knocked down by lentivirus to detect the proliferation, cycle, apoptosis of FaDu and CNE-2Z cells, and finally by PathScan intracellular signaling array reagent to detect the apoptotic protein content.
Results: Based on the pan-cancer analysis, we found that elevated expression of NUDT21 in most cancers was significantly correlated with TMB, MSI, neoantigens and chromosomal ploidy, and in epigenetics, elevated NUDT21 expression was strongly associated with genomic stability, mismatch repair genes, tumor stemness, and RNA methylation. Based on immunosuppressive score, we found that NUDT21 plays an essential role in the immunosuppressive environment by suppressing immune checkpointing effect in most cancers. In addition, using HHNSCC as a study target, PCR and pathological detection of NUDT21 in tumor tissues was significantly increased than that in paracancerous normal tissues. In vitro cellular assays, silencing NUDT21 inhibited proliferation and promoted apoptosis in FaDu and CNE-2Z cells, and blocked the cell cycle in the G2/M phase. Therefore, the experiments confirmed that NUDT21 promotes the proliferation of FaDu by suppressing the expression of apoptotic.
Abbreviations
HHNSCC: Human head and neck squamous cell carcinoma; HHNC: Human head and neck cancer; PFI: Shorter progression-free intervals; TMB: Tumor mutational burden; MSI: Microsatellite instability; HRD: Homologous recombination defect; TME: The tumor microenvironment; MDSCs: Myeloid suppressor cells; TAM: Tumor-associated macrophages; CAF: Cancer-associated fibroblasts; GSEA: Gene set enrichment analysis.