Analysis of the Mechanism of RAD18 in Glioma

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud Rent for 48h to view Buy Cloud Access for unlimited viewing via different devices Synchronizing in the ReadCube Cloud Printing and saving restrictions apply Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: July 05, 2021
Accepted: October 28, 2021
Published online: April 01, 2022

Number of Print Pages: 11
Number of Figures: 7
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: https://www.karger.com/NIM

Abstract

Introduction: This study aimed to evaluate the regulatory mechanism of RAD18 in glioma development. Methods: RAD18 expression was compared in glioma tumors and normal samples. Furthermore, we investigated the association between gene transcription and clinical factors in glioma samples, followed by functional enrichment analysis, screening for key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, immune infiltration analysis of high and low RAD18 expression groups, and correlation analysis of quantified KEGG signaling pathways and immune cell types. Results: The expression of RAD18 was upregulated in gliomas. Moreover, RAD18 expression was significantly correlated with age, tumor grade, and histological subtype. Notably, patients with gliomas with high RAD18 expression levels had worse overall survival. Functional enrichment analysis showed that RAD18 was significantly related to biological processes, such as cell division, chemical synaptic transmission, and mitotic nuclear division, and KEGG pathways such as cell cycle, oxidative phosphorylation, and extracellular matrix (ECM)-receptor interaction. The infiltration of five immune cells (plasma B cells, naive B cells, resting CD4+ memory T cells, monocytes, and M1 macrophages) was significantly different between the high and low RAD18 expression groups, and this difference was significantly related to key KEGG pathways, such as neuroactive ligand-receptor interaction and ECM-receptor interaction. Conclusion: RAD18 may serve as a target for glioma treatment and as a key regulator of glioma development.

© 2022 S. Karger AG, Basel

References Wang H, Xu T, Huang Q, Jin W, Chen J. Immunotherapy for malignant glioma: current status and future directions. Trends Pharmacol Sci. 2020;41(2):123–38. Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun. 2020;8(1):30. Diamandis P, Aldape K. World health organization 2016 classification of central nervous system tumors. Neurol Clin. 2018;36(3):439–47. Schiff D, Brown PD, Giannini C. Outcome in adult low-grade glioma: the impact of prognostic factors and treatment. Neurology. 2007;69(13):1366–73. Manoharan N, Choi J, Chordas C, Zimmerman MA, Scully J, Clymer J, et al. Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma. J Neurooncol. 2020;149(2):253–62. Lieberman F. Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials. F1000Res. 2017;6:1892. Jones JS, Weber S, Prakash L. The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains potential zinc finger domains for nucleic acid binding and a putative nucleotide binding sequence. Nucleic Acids Res. 1988;16(14B):7119–31. Kermi C, Prieto S, van der Laan S, Tsanov N, Recolin B, Uro-Coste E, et al. RAD18 is a maternal limiting factor silencing the UV-dependent dna damage checkpoint in xenopus embryos. Dev Cell. 2015;34(3):364–72. Wong RP, Aguissa-Toure AH, Wani AA, Khosravi S, Martinka M, Martinka M, et al. Elevated expression of Rad18 regulates melanoma cell proliferation. Pigment Cell Melanoma Res. 2012;25(2):213–8. Zhou J, Zhang S, Xie L, Liu P, Xie F, Wu J, et al. Overexpression of DNA polymerase iota (Poliota) in esophageal squamous cell carcinoma. Cancer Sci. 2012;103(8):1574–9. Xie C, Wang H, Cheng H, Li J, Wang Z, Yue W. RAD18 mediates resistance to ionizing radiation in human glioma cells. Biochem Biophys Res Commun. 2014;445(1):263–8. Wu B, Wang H, Zhang L, Sun C, Li H, Jiang C, et al. High expression of RAD18 in glioma induces radiotherapy resistance via down-regulating P53 expression. Biomed Pharmacother. 2019;112:108555. Lou P, Zou S, Shang Z, He C, Gao A, Hou S, et al. RAD18 contributes to the migration and invasion of human cervical cancer cells via the interleukin-1beta pathway. Mol Med Rep. 2019;20(4):3415–23. Nayak RC, Cancelas JA. Ubiquitination is not omnipresent in myeloid leukemia. Haematologica. 2019;104(9):1694–6. Mantovani A, Marchesi F, Portal C, Allavena P, Sica A. Linking inflammation reactions to cancer: novel targets for therapeutic strategies. Adv Exp Med Biol. 2008;610:112–27. Michelson N, Rincon-Torroella J, Quiñones-Hinojosa A, Greenfield JP. Exploring the role of inflammation in the malignant transformation of low-grade gliomas. J Neuroimmunol. 2016;297:132–40. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98–102. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649–58. Thul PJ, Lindskog C. The human protein atlas: a spatial map of the human proteome. Protein Sci. 2018;27(1):233–44. Gao X, Chen Y, Chen M, Wang S, Wen X, Zhang S. Identification of key candidate genes and biological pathways in bladder cancer. PeerJ. 2018;6:e6036. Wang L, Cao C, Ma Q, Zeng Q, Wang H, Cheng Z, et al. RNA-seq analyses of multiple meristems of soybean: novel and alternative transcripts, evolutionary and functional implications. BMC Plant Biology. 2014;14:169. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50. Li BL, Wan XP. Prognostic significance of immune landscape in tumour microenvironment of endometrial cancer. J Cell Mol Med. 2020;24(14):7767–77. Hu D, Zhou M, Zhu X. Deciphering immune-associated genes to predict survival in clear cell renal cell cancer. Biomed Res Int. 2019;2019:2506843. Kanzaki H, Ouchida M, Hanafusa H, Yamamoto H, Suzuki H, Yano M, et al. The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer. J Cancer Res Clin Oncol. 2008;134(2):211–7. Kanzaki H, Ouchida M, Hanafusa H, Sakai A, Yamamoto H, Suzuki H, et al. Single nucleotide polymorphism in the RAD18 gene and risk of colorectal cancer in the Japanese population. Oncol Rep. 2007;18(5):1171–5. Xie C, Lu D, Xu M, Qu Z, Zhang W, Wang H. Knockdown of RAD18 inhibits glioblastoma development. J Cell Physiol. 2019;234(11):21100–12. Baatar S, Bai T, Yokobori T, Gombodorj N, Nakazawa N, Ubukata Y, et al. High RAD18 expression is associated with disease progression and poor prognosis in patients with gastric cancer. Ann Surg Oncol. 2020;27(11):4360–8. Zou S, Yang J, Guo J, Su Y, He C, Wu J, et al. RAD18 promotes the migration and invasion of esophageal squamous cell cancer via the JNK-MMPs pathway. Cancer Lett. 2018;417:65–74. Golias CH, Charalabopoulos A, Charalabopoulos K. Cell proliferation and cell cycle control: a mini review. Int J Clin Pract. 2004;58(12):1134–41. Domingues P, Gonzalez-Tablas M, Otero A, Pascual D, Miranda D, Ruiz L, et al. Tumor infiltrating immune cells in gliomas and meningiomas. Brain Behav Immun. 2016;53:1–15. Liang R, Chen N, Li M, Wang X, Mao Q, Liu Y. Significance of systemic immune-inflammation index in the differential diagnosis of high- and low-grade gliomas. Clin Neurol Neurosurg. 2018;164:50–2. Lu J, Li H, Chen Z, Fan L, Feng S, Cai X, et al. Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma. Cancer Cell Int. 2019;19:265. Xiong Y, Wang K, Zhou H, Peng L, You W, Fu Z. Profiles of immune infiltration in colorectal cancer and their clinical significant: a gene expression-based study. Cancer Med. 2018;7(9):4496–508. Zhou Z, Wen L, Lai M, Shan C, Wang J, Wang R, et al. Increased M1 macrophages infiltration correlated with poor survival outcomes and radiation response in gliomas. Dose Response. 2020;18(4):1559325820964991. Tian Y, Ke Y, Ma Y. High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment. PeerJ. 2020;8:e9038. Hu G, Wang R, Wei B, Wang L, Yang Q, Kong D, et al. Prognostic markers identification in glioma by gene expression profile analysis. J Comput Biol. 2020;27(1):81–90. Mukhtar I, Wu S, Wei S, Chen R, Cheng Y, Liang C, et al. Transcriptome profiling revealed multiple rqua genes in the species of spirostomum (Protozoa: Ciliophora: Heterotrichea). Front Microbiol. 2020;11:574285. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: July 05, 2021
Accepted: October 28, 2021
Published online: April 01, 2022

Number of Print Pages: 11
Number of Figures: 7
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: https://www.karger.com/NIM

留言 (0)

沒有登入
gif