PAICS is related to glioma grade and can promote glioma growth and migration

Du, Botao; Zhang, Zheying; Di, Wenyu; Xu, Wenzhong; Yang, Lei; Zhang, Shitao; He, Guoyang; Yang, Rui; Wang, Maode

doi:10.1111/jcmm.16647

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…As a key regulatory enzyme involved in the de novo purine biosynthesis pathway, PAICS serves an important role in regulating cell proliferation, growth, and apoptosis. PAICS promotes tumor cells proliferation and migration, whereas the knockdown of PAICS leads to tumor cell cycle arrest and apoptosis 30,39 . In this study, shRNA‐mediated PAICS knockdown showed significant suppression on the viability and proliferation, while induction on apoptosis of EGFR wild‐type NSCLC cells.…”

Section: Discussionmentioning

confidence: 54%

“…PAICS is overexpressed in glioma, breast cancer, pancreatic cancer, gastric cancer, prostate cancer, bladder cancer, and colorectal cancer, and its high expression is closely related to the poor survival of tumor patients. [29][30][31][32][33][34] However, a recent paper by Kobayashi et al 29 analyzed 1659 colorectal tumor samples demonstrated a reduction of PAICS due to genetic deletion of chromosome 4q during colorectal tumor progression and metastasis. Correspondingly, loss of PAICS is also correlated with poor relapse-free survival in stage III colorectal tumor patients.…”

Section: Discussionmentioning

confidence: 99%

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Genome‐scale CRISPR–Cas9 screen identifies PAICS as a therapeutic target for EGFR wild‐type non‐small cell lung cancer

Li,

Zhu,

Mao

et al. 2024

MedComm

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Epidermal growth factor receptor‐targeted (EGFR‐targeted) therapies show promise for non‐small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild‐type NSCLC. A genome‐wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild‐type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild‐type NSCLC cells. Additionally, PAICS silencing led to cell‐cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild‐type NSCLC. PAICS silencing also caused DNA damage and cell‐cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K–AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild‐type NSCLC and represents a potential therapeutic target for this disease.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Genome‐scale CRISPR–Cas9 screen identifies PAICS as a therapeutic target for EGFR wild‐type non‐small cell lung cancer

Li,

Zhu,

Mao

et al. 2024

MedComm

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“…One study has reported that PAICS can promote tumor proliferation and migration in neuroblastoma [32], though it has also been shown to play an important role in a variety of tumors [4][5][6]. Our previous study also found that PAICS plays an oncogene role in glioma [9]. Bioinformatics analysis indicated that SPI1 can bind to the PAICS promoter region.…”

Section: Discussionmentioning

confidence: 81%

“…Numerous studies demonstrated that PAICS can promote the proliferation and migration of many tumors [3][4][5][6][7][8]. Our previous study also found that PAICS plays an oncogene role in glioma [9]. In this project, we intend to further study the transcriptional regulation of SPI1 and PAICS through luciferase assay, gene transfection technology, Western blot and other techniques.…”

Section: Introductionmentioning

confidence: 97%

Study on the role of transcription factor SPI1 in the development of glioma

Gao

Qin

et al. 2022

Chin Neurosurg Jl

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Background Glioma is a common malignant brain tumor. The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma. Methods SPI1 expression in glioma was identified using qRT-PCR and Western blotting. Cell proliferation was assessed using the CCK8 assay. Transwell and wound healing assays were utilized to evaluate cell migration. Additionally, cell cycle and apoptosis were detected using flow cytometry. Results We observed that the expression level of SPI1 was up-regulated in glioma tissues, compared to normal tissues. Furthermore, we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro. Flow cytometry results demonstrate that, compared to si-NC cells, si-SPI1 cells stagnated in the G1 phase, and down-regulation of SPI1 expression is able to increase rates of apoptosis. Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS. Conclusions Our results suggest that SPI1 can promote proliferation and migration of glioma. Furthermore, SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.

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“…In fact, purine-metabolizing enzymes also participate in other biological processes. For instance, CD39 and ADA are involved in immune regulation [ 18 , 58 , 59 , 83 ]; IMPDH carries out the function of a transcription factor [ 282 ]; SAM Domain And HD Domain-Containing Protein-1 assists in regulating the cell cycle [ 283 ] and phosphoribosylaminoimidazole succinocarboxamide synthetase is correlated with DNA damage repair [ 284 , 285 ]. It can help to identify new interventions in tumor process if we focus on purine metabolic processes and understand the mechanisms of action of the relevant enzymes as well as the interaction with other biological processes.…”

Section: Discussionmentioning

confidence: 99%

Targeting purine metabolism in ovarian cancer

et al. 2022

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Purine, an abundant substrate in organisms, is a critical raw material for cell proliferation and an important factor for immune regulation. The purine de novo pathway and salvage pathway are tightly regulated by multiple enzymes, and dysfunction in these enzymes leads to excessive cell proliferation and immune imbalance that result in tumor progression. Maintaining the homeostasis of purine pools is an effective way to control cell growth and tumor evolution, and exploiting purine metabolism to suppress tumors suggests interesting directions for future research. In this review, we describe the process of purine metabolism and summarize the role and potential therapeutic effects of the major purine-metabolizing enzymes in ovarian cancer, including CD39, CD73, adenosine deaminase, adenylate kinase, hypoxanthine guanine phosphoribosyltransferase, inosine monophosphate dehydrogenase, purine nucleoside phosphorylase, dihydrofolate reductase and 5,10-methylenetetrahydrofolate reductase. Purinergic signaling is also described. We then provide an overview of the application of purine antimetabolites, comprising 6-thioguanine, 6-mercaptopurine, methotrexate, fludarabine and clopidogrel. Finally, we discuss the current challenges and future opportunities for targeting purine metabolism in the treatment-relevant cellular mechanisms of ovarian cancer. Graphical Abstract

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PAICS is related to glioma grade and can promote glioma growth and migration

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 28 publications

Genome‐scale CRISPR–Cas9 screen identifies PAICS as a therapeutic target for EGFR wild‐type non‐small cell lung cancer

Genome‐scale CRISPR–Cas9 screen identifies PAICS as a therapeutic target for EGFR wild‐type non‐small cell lung cancer

Study on the role of transcription factor SPI1 in the development of glioma

Targeting purine metabolism in ovarian cancer

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