切换至 "中华医学电子期刊资源库"

中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (06) : 942 -948. doi: 10.3877/cma.j.issn.1674-6902.2025.06.015

论著

嘌呤生物合成关键酶PAICS在肺腺癌中的表达及功能研究
唐林娟1, 王槿樾2, 王欣2, 黄娜2, 杨凯2,()   
  1. 1610404 成都,金堂县第二人民医院检验科
    2610500 成都,成都医学院第一附属医院呼吸与危重症医学科
  • 收稿日期:2025-02-28 出版日期:2025-12-25
  • 通信作者: 杨凯
  • 基金资助:
    成都医学院科技基金项目(CYZYB23-23)

Expression and functional significance of the de novo purine synthesis enzyme PAICS gene in lung adenocarcinoma

Linjuan Tang1, Jinyue Wang2, Xin Wang2, Na Huang2, Kai Yang2,()   

  1. 1Department of Laboratory Medicine, Jintang County Second People′s Hospital, Chengdu 610404, China
    2Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China
  • Received:2025-02-28 Published:2025-12-25
  • Corresponding author: Kai Yang
引用本文:

唐林娟, 王槿樾, 王欣, 黄娜, 杨凯. 嘌呤生物合成关键酶PAICS在肺腺癌中的表达及功能研究[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(06): 942-948.

Linjuan Tang, Jinyue Wang, Xin Wang, Na Huang, Kai Yang. Expression and functional significance of the de novo purine synthesis enzyme PAICS gene in lung adenocarcinoma[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(06): 942-948.

目的

探讨磷酸核糖氨基咪唑琥珀酰胺合成酶(phosphoribosylaminoimidazole succinocarboxamide synthetase, PAICS)在肺腺癌中的表达,分析作用及机制。

方法

利用GEO、GEPIA及HPA数据库分析PAICS在肺腺癌与癌旁组织中表达差异;通过GEPIA数据库和Kaplan-Meier Plotter平台分析PAICS高表达与肺腺癌预后关系;基于LinkedOmics数据库分析获取肺腺癌中与PAICS呈显著相关的共表达基因,进行GO聚类分析和KEGG信号通路富集分析;TIMER数据库分析PAICS与肺腺癌免疫浸润关系。PAICS siRNA转染培养肺癌细胞株A549、H1299,观察下调PAICS表达对肺癌细胞增值活力、细胞迁移能力、细胞周期蛋白基因CCNA2、CCNB1、CCNB2及免疫检查点基因程序性死亡配体-1(programmed cell death ligand 1, PD-L1) mRNA表达的影响。

结果

数据库分析显示,PAICS在肺腺癌组织中表达显著上调(P<0.001),PAICS高表达与总体存活率呈显著负相关(P<0.001)。TIMER数据库分析显示PAICS表达量与肿瘤微环境中肿瘤细胞纯度呈显著正相关(r=0.13,P<0.01),与B细胞(r=-0.236,P<0.01)、CD4 T细胞(r=-0.173,P<0.01)、巨噬细胞(r=-0.156,P<0.01)和树突状细胞(r=-0.131,P<0.01)表达丰度呈显著负相关;PAICS相关基因的功能富集分析显示,PAICS相关基因可通过细胞周期和增殖分裂过程等参与肺腺癌发生。培养肺癌细胞株A549、H1299中PAICS siRNA转染显著抑制肺癌细胞增殖活力(P<0.01)和迁移能力(P<0.01),降低癌细胞中细胞周期蛋白基因CCNA2(P<0.05)、CCNB1(P<0.05)、CCNB2(P<0.05)及免疫检查点基因PD-L1表达(P<0.05)。裸鼠A549细胞种植瘤模型实验显示,PAICS siRNA转染显著减小裸鼠种植瘤的瘤体体积(P<0.05)和质量(P<0.05)。

结论

PAICS在肺腺癌发生发展中起重要作用。PAICS可作为肺腺癌的预后指标和潜在靶点,具有前瞻性临床意义。

Objective

To investigate the expression and functional significance of phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) in human lung adenocarcinoma and its mechanisms.

Methods

The GEO, GEPIA, and HPA databases were used to investigate the difference in expression of PAICS in lung adenocarcinoma compared with paracancerous tissues. The prognosis value of PAICS in patients with lung adenocarcinoma was evaluated by the GEPIA database and Kaplan-Meier Plotter platform. PAICS-associated co-expressed genes were obtained from the LinkedOmics database and used to perform gene ontology (GO) enrichment and KEGG enrichment analysis. The TIMER database was used to evaluate the relationship between PAICS and immune infiltration level of lung adenocarcinoma. Cultured A549 and H1299 cell lines were transfected with PAICS siRNA to investigate the effects of PAICS downregulation on the proliferation and migration of lung adenocarcinoma cell lines and the mRNA expression of CCNA2, CCNB1, CCNB2, and immune checkpoint gene PD-L1 in A549 and H1299.

Results

Multiple databases analysis revealed that PAICS expression was upregulated in patients with lung adenocarcinoma (P<0.001). High PAICS expression was negatively correlated with overall survival(P<0.001). The TIMER database revealed that the expression of PAICS in patients with lung adenocarcinoma were significantly and positively correlated with tumor cell purity (r= 0.13, P<0.01) but negatively correlated with B cells (r=-0.236, P<0.01), CD4+ T cells (r=-0.173, P<0.01), macrophages (r=-0.156, P<0.01), and dendritic cells (r=-0.131, P<0.01) in tumor microenvironment. GO enrichment and KEGG enrichment analyses indicated that PAICS-associated co-expressed genes were involved in the pathogenesis of lung adenocarcinoma through the regulation of cell cycle and cell mitosis. In cultured A549 and H1299 cell lines, PAICS siRNA transfection markedly attenuated the proliferation (P<0.01) and migration (P<0.01) of both cell lines and downregulated the expression of the genes encoding cyclin CCNA2 (P<0.05), CCNB1 (P<0.05), CCNB2 (P<0.05), and PD-L1 (P<0.05). In a xenograft mouse model transplanted with A549 cells, PAICS siRNA transfection markedly decreased the tumor size (P<0.05) and tumor weight (P<0.05).

Conclusion

PAICS plays a key role in the pathogenesis of lung adenocarcinoma. PAICS may serve as a prognostic indicator and potential target of lung adenocarcinoma, it with prospective clinical significance.

图1 PAICS在肺腺癌组织中表达及与预后关系A为GSE229705数据集肺腺癌组织中PAICS表达;B为GEPIA数据库肺腺癌组织中PAICS表达;C为GEPIA数据库肺腺癌组织癌症不同分期PAICS表达;D为HPA数据库中肺腺癌和癌旁组织PAICS表达的免疫组织化学染色切片注:relative expression为相对表达;A、B中Normal为癌旁正常组织;LUAD为肺腺癌组织;D中Normal为HPA数据库正常人肺组织,patient id为患者ID,sex为性别,female为女性,age为年龄,staining为染色,instensity为强度,moderate为中度,quantity为数量,low为低,high为高,strong为重度
图2 PAICS siRNA转染对肺癌细胞增殖活力、迁移特性、周期蛋白及免疫检查点基因mRNA表达及成瘤特性的影响。图A为培养肺癌细胞系中PAICS mRNA表达量;图B为培养肺癌细胞增殖活力;图C、D为培养肺癌细胞系迁移能力;图E、F为培养肺癌细胞系中细胞周期蛋白CCNA2、CCNB1、CCNB2及免疫检查点基因PD-L1 mRNA表达量注:expression为表达;fold of control为相对对照组;cell viability为细胞活力;migrated cell number为迁移细胞数;NC-siR为siRNA阴性对照组;PAICS-siR为PAICS siRNA组;CCNA2为细胞周期蛋白A2;CCNB1为细胞周期蛋白B1;CCNB2为细胞周期蛋白B2;PD-L1为程序性死亡配体-1。*P<0.05 vs. NC-siR
1
喻星豪,黄娜,刘罡. 肺癌的靶向与免疫联合治疗的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(2): 330-333.
2
Thai AA, Solomon BJ, Sequist LV, et al. Lung cancer[J]. Lancet, 2021, 398(10299): 535-554.
3
Patel SA, Weiss J. Advances in the Treatment of non-small cell lung cancer: Immunotherapy[J]. Clin Chest Med, 2020, 41(2): 237-247.
4
Liu X, Yu Y, Wang M, et al. The mortality of lung cancer attributable to smoking among adults in China and the United States during 1990-2017[J]. Cancer Commun (Lond), 2020, 40(11): 611-619.
5
Huo A, Xiong X. PAICS as a potential target for cancer therapy linking purine biosynthesis to cancer progression [J]. Life Sci, 2023, 331: 122070.
6
Lang L, Tao J, Yang C, et al. Tumor suppressive role of microRNA-4731-5p in breast cancer through reduction of PAICS-induced FAK phosphorylation [J]. Cell Death Discov, 2022, 8(1): 154.
7
Du B, Zhang Z, Di W, et al. PAICS is related to glioma grade and can promote glioma growth and migration [J]. J Cell Mol Med, 2021, 25(16): 7720-7733.
8
Kobayashi Y, Kumamoto K, Okayama H, et al. Downregulation of PAICS due to loss of chromosome 4q is associated with poor survival in stage Ⅲ colorectal cancer [J]. PLoS One, 2021, 16(2): e0247169.
9
Xu R, Han F, Zhao Y, et al. Role of CENPL, DARS2, and PAICS in determining the prognosis of patients with lung adenocarcinoma [J]. Transl Lung Cancer Res, 2024, 13(10): 2729-2745.
10
Raman P, Zimmerman S, Rathi KS, et al. A comparison of survival analysis methods for cancer gene expression RNA-Sequencing data [J]. Cancer Genet, 2019, 235-236: 1-12.
11
Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses [J]. Nucleic Acids Res, 2017, 45(W1): W98-W102.
12
Gyorffy B. Transcriptome-level discovery of survival-associated biomarkers and therapy targets in non-small-cell lung cancer[J]. Br J Pharmacol, 2024, 181(3): 362-374.
13
Tran DH, Kim D, Kesavan R, et al. De novo and salvage purine synthesis pathways across tissues and tumors [J]. Cell, 2024, 187(14): 3602-3618.
14
Barfeld SJ, Fazli L, Persson M, et al. Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer[J]. Oncotarget, 2015, 6(14): 12587-12602.
15
Chakravarthi B, Rodriguez Pena MDC, Agarwal S, et al. A role for de novo purine metabolic enzyme PAICS in bladder cancer progression [J]. Neoplasia, 2018, 20(9): 894-904.
16
Yamauchi T, Miyawaki K, Semba Y, et al. Targeting leukemia-specific dependence on the de novo purine synthesis pathway [J]. Leukemia, 2022, 36(2): 383-393.
17
Goswami MT, Chen G, Chakravarthi BV, et al. Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer [J]. Oncotarget, 2015, 6(27): 23445-23461.
18
Aluksanasuwan S, Somsuan K, Ngoenkam J, et al. Knockdown of heat shock protein family D member 1 (HSPD1) in lung cancer cell altered secretome profile and cancer-associated fibroblast induction[J]. Biochim Biophys Acta Mol Cell Res, 2024, 1871(5): 119736.
19
Sun H, Zhang H, Yan Y, et al. NCAPG promotes the oncogenesis and progression of non-small cell lung cancer cells through upregulating LGALS1 expression[J]. Mol Cancer, 2022, 21(1): 55.
20
Feng YY, Liu CH, Xue Y, et al. MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients [J]. Gene, 2020, 730: 144316.
21
Altorkin K, Markowitz GJ, Gao D, et al. The lung microenvironment:an important regulator of tumour growth and metastasis[J]. Nat Rev Cancer, 2019, 19(1): 9-31.
22
Jones HP, Aldridge B, Boss-Williams K, et al. A role for B cells in facilitating defense against an NK cell-sensitive lung metastatic tumor is revealed by stress [J]. J Neuroimmunol, 2017, 313: 99-108.
23
Lee HE, Luo L, KRoneman T, et al. Increased plasma cells and decreased B-cells in tumor infiltrating lymphocytes are associated with worse survival in lung adenocarcinomas [J]. J Clin Cell Immunol, 2020, 11(1): 584.
24
Chang X, Zhao J, Zhou Y, et al. MiR-7 deficiency promotes Th1 polarization of CD4(+)T cells and enhances the antitumor effect in adoptive cell therapy for lung cancer [J]. Immunol Res, 2024, 72(1): 134-146.
25
Aktar T, Modak S, Majumder D, et al. A detailed insight into macrophages′role in shaping lung carcinogenesis [J]. Life Sci, 2024, 352: 122896.
26
De Oliveira JB, Silva SB, Fernandes IL, et al. Dendritic cell-based immunotherapy in non-small cell lung cancer: a comprehensive critical review [J]. Front Immunol, 2024, 15: 1376704.
27
Chotiner JY, Wolgemuth DJ, Wang PJ. Functions of cyclins and CDKs in mammalian gametogenesisdagger [J]. Biol Reprod, 2019, 101(3): 591-601.
28
Huang Y, Zhong L, Nie K, et al. Identification of LINC00665-miR-let-7b-CCNA2 competing endogenous RNA network associated with prognosis of lung adenocarcinoma [J]. Sci Rep, 2021, 11(1): 4434.
29
Wang X, Xiao H, Wu D, et al. miR-335-5p regulates cell cycle and metastasis in lung adenocarcinoma by targeting CCNB2 [J]. Onco Targets Ther, 2020, 13: 6255-6263.
30
Bao B, Yu X, Zheng W. MiR-139-5p targeting CCNB1 modulates proliferation, migration, invasion and cell cycle in lung adenocarcinoma [J]. Mol Biotechnol, 2022, 64(8): 852-860.
31
Kim DH, Kim H, Choi YJ, et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer [J]. Exp Mol Med, 2019, 51(8): 1-13.
[1] 汪秀静, 董梦婷, 盛佳钰, 江科. CDK4/6抑制剂致乳腺癌患者白癜风样皮损一例[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(05): 311-313.
[2] 赵诗迪, 杨姣, 周妍, 范园, 杨谨. CDK4/6抑制剂在激素受体阳性晚期乳腺癌一线治疗中的挑战及进展后策略[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(05): 257-266.
[3] 李乐桐, 林加曼, 王强. 1-磷酸鞘氨醇受体1 在乳腺癌患者中的表达及其对预后和免疫浸润的影响[J/OL]. 中华危重症医学杂志(电子版), 2025, 18(02): 105-114.
[4] 黄莹, 李璇, 刘梦杨, 彭桂林, 徐鑫, 韦兵, 杨超. 靶向联合治疗双肺移植术后KRAS和BRAF基因双突变晚期肺腺癌一例[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 298-301.
[5] 李艳鸿, 张海颖, 邓丽娜, 张雯文, 贺梦颖, 郭旭萌, 佘静亚. 血清tRF-Lys-CTT表达水平预测肺腺癌患者术后复发的临床意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(06): 936-941.
[6] 曾慧, 刘朝朝, 牛雷, 邓雅洁, 徐礼霞, 沙莎. 早期肺腺癌血清外泌体miRNA特征谱及诊断标志物筛选研究[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(06): 891-896.
[7] 赵才林, 向青, 钱航, 施雯, 邱凌霄, 王斌. 基于生物信息学解析急性肺损伤/急性呼吸窘迫综合征铁死亡枢纽基因及其与免疫分型的关系[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(04): 503-509.
[8] 夏祯祎, 刘懿, 丁俞成, 袁宏霞, 李晓燕, 陈田. circUBAP2L 通过hsa-let-7c/GAD1 轴调控肺腺癌1-甲基组氨酸和二甲基甘氨酸的机制分析[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 273-278.
[9] 李爱科, 李富博, 赵继伟, 张立广, 董怡, 梁宗英, 于晓磊, 杜新生. 血清黑素瘤抗原A3 水平与肺腺癌预后的关系分析[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 236-240.
[10] 应允丽, 赵凤德, 韩明锋, 李明, 申辉. 肺腺癌患者衰弱状态与预后关系分析[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(01): 131-134.
[11] 汪艳, 孙美玲, 闵凌峰. 基于TCGA 数据库肺腺癌铁死亡相关基因CA9 的鉴定[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(06): 888-894.
[12] 袭厚榕, 隋晓峰. 基于生物信息学分析乳腺癌组织STIP1表达在免疫浸润中的作用[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(04): 208-216.
[13] 郑希彦, 吴润鹏, 杜飞, 谢玉芬, 王平根, 张广权, 翟航, 何函樨, 李瑞曦. 基于生信分析SLC29A3 在肝癌中的表达及临床意义[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(02): 290-295.
[14] 马钰杰, 游雨禾, 朴哲, 薛洪省, 曹文军, 王珍, 赵志龙. 人工智能在肺结节预测模型中应用的研究现状[J/OL]. 中华胸部外科电子杂志, 2025, 12(01): 39-48.
[15] 崔世军, 黄志宁, 王高祥, 吴明胜, 孙效辉, 徐美清, 解明然. 不同手术方式对≤2 cm外周型肺腺癌患者肺部术后慢性咳嗽对比分析[J/OL]. 中华胸部外科电子杂志, 2025, 12(01): 24-32.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?