Clinical Research

The expression of PCBP1 in gastric cancer and its relationship with ferroptosis factor STUB1

  • Xuman LU ,
  • Zhengyi SHI ,
  • Yuanrui LEI ,
  • Haibin HUANG ,
  • Renmiao DENG ,
  • Xudong DONG ,
  • Yuliang HUANG ,
  • Fanbiao KONG ,
  • Xiaotong. WANG
Expand
  • *.Graduate School of Guangxi University of Traditional Chinese Medicine,Nanning 530000,Guangxi,China
    *.Department of Gastrointestinal,Hernia and Intestinal Fistula Surgery,Guangxi Zhuang Autonomous Region People 's Hospital,Guangxi Academy of Medical Sciences,Nanning 530021,Guangxi,China

Received date: 2025-06-18

  Online published: 2025-10-10

Abstract

Objective To investigate the expression characteristics of poly (rC)-binding protein 1 (PCBP1) in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification, and to identify its relationship with STIP1 homology and U-Box containing protein 1 (STUB1). Specifically, this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer. Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website. KEGG pathway enrichment analysis was performed using gastric cancer data (STAD) in the TCGA (the Cancer Genome Atlas) database, and its potential mechanism was determined. The main regulatory factor STUB1 was found in the ferroptosis regulatory pathway. Subsequently, PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry. The collected cases were grouped according to different degrees of differentiation, age, gender, tumor size, depth of tumor invasion, TNM stage and pathological morphology. The positive expression rates of PCBP1 and STUB1 were observed. The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test. Finally, the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored. Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7 %, which was significantly higher than that in adjacent tissues (48.5%). The positive expression rate of STUB1 in cancer tissues was 39.4 %, which was lower than that in adjacent tissues (54.5 %), statistically significant difference (P < 0.05). The positive expression rate of PCBP1 was correlated with tumor differentiation, lymph node metastasis and Lauren classification (P < 0.05), but not with patient's age, gender, depth of invasion, clinical stage, nerve infiltration, and intravascular tumor thrombus (P > 0.05). The positive expression rate of STUB1 was correlated with tumor differentiation, depth of invasion, lymph node metastasis and Lauren classification (P < 0.05). The Spearman correlation coefficient between PCBP1 (cancer) and STUB1 (cancer) was -0.413, with P = 0.017 (P < 0.05), indicating that there was a significant negative correlation between them. Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway. Theoretically, it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.

Cite this article

Xuman LU , Zhengyi SHI , Yuanrui LEI , Haibin HUANG , Renmiao DENG , Xudong DONG , Yuliang HUANG , Fanbiao KONG , Xiaotong. WANG . The expression of PCBP1 in gastric cancer and its relationship with ferroptosis factor STUB1[J]. The Journal of Practical Medicine, 2025 , 41(19) : 3026 -3033 . DOI: 10.3969/j.issn.1006-5725.2025.19.010

References

[1] BRAY F, LAVERSANNE M, SUNG H, et al. Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin,2024,74(3):229-263. doi:10.3322/caac.21834
[2] 丁平安,杨沛刚,田园,等. 胃癌伴左锁骨上淋巴结转移患者的临床病理特征及预后 [J]. 实用医学杂志, 2021, 37 (13): 1695-1700.
[3] NAYAK A, KUMAR S, SINGH S P, et al. Oncogenic potential of ATAD2 in stomach cancer and insights into theprotein-protein interactions at its AAA?+?ATPase domain and bromodomain[J].J Biomol Struct Dyn,2022,40(12):5606-5622. doi:10.1080/07391102.2021.1871959
[4] 贾冰冰, 叶梦, 霍丽蓉. PCBP1相关生物功能的研究进展[J]. 医学研究杂志, 2018, 47 (9): 176-179+135.
[5] SHI H, BENCZE K Z, STEMMLER T L,et al. A cytosolic iron chaperone that delivers iron to ferritin[J]. Science, 2008,320(5880):1207-1210. doi:10.1126/science.1157643
[6] WANG X Q, FAN A Q, HONG L. LncRNA MIR210HG promotes the proliferation of colon cancer cells by inhibiting ferroptosis through binding to PCBP1[J]. Sci Rep,2025,15(1):871. doi:10.1038/s41598-025-85321-7
[7] WEI F, MENG Y, ZHU D X, et al. Mechanism and role of ferroptosis in the development of gastric cancer[J]. Clin Exp Med,2025,25(1):182. doi:10.1007/s10238-025-01722-y
[8] ZHANG L, LUO Y L, XIANG Y, et al. Ferroptosis inhibitors: Past, present and future[J]. Front Pharmacol,2024,15:1407335. doi:10.3389/fphar.2024.1407335
[9] CUI S, SIMMONS G J, VALE G,et al. FAF1 blocks ferroptosis by inhibiting peroxidation of polyunsaturated fatty acids[J]. Proc Natl Acad Sci USA,2022,9:e2107189119. doi:10.1073/pnas.2107189119
[10] SHAO M, QI K, WANG L,et al. E3 ubiquitin ligase CHIP interacts with transferrin receptor 1 for degradation and promotes cell proliferation through inhibiting ferroptosis in hepatocellular carcinoma[J]. Cell Signal,2024,118:111148. doi:10.1016/j.cellsig.2024.111148
[11] 张银亮,骆泽谭,赵睿,等. 血根碱通过调控STUB1/GPX4诱导直肠癌细胞发生铁死亡[J]. 南方医科大学学报,2024,44(8):1537-1544.
[12] 王衍颜,张军,毛沛,等. 肺鳞状细胞癌组织PCBP1、GPSM2表达与EMT、临床病理特征和预后的关系[J]. 现代生物医学进展,2024,24(19):3654-3656+3666.
[13] 郑荣寿,张思维,孙可欣,等. 2016年中国恶性肿瘤流行情况分析[J].中华肿瘤杂志,2023,45(3):212-220. doi:10.3760/cma.j.cn112152-20220922-00647
[14] 覃黎明,周子寒,曹骥,等. 2011—2018年广西胃癌流行特征及疾病负担分析[J]. 中国癌症防治杂志,2024,16(02):172-179.
[15] 范文凭,林琳,刘江美,等.基于GBD数据分析1990—2019年中国恶性肿瘤疾病负担趋势[J].中国肿瘤,2024,33(1):20-26.
[16] CHOI H S, HWANG C K, SONG K Y,et al. Poly(C)-binding proteins as transcriptional regulators of gene expression[J]. Biochem Biophys Res Commun,2009,380(3):431-436. doi:10.1016/j.bbrc.2009.01.136
[17] 杨杰,李卫,刘贺,等. 应用酵母双杂交筛选人胃癌耐药细胞SIVA-1基因相互作用蛋白[J]. 现代肿瘤医学,2023,31(5):806-811.
[18] KONG F B, SHI Z Y, HUANG Y L,et al. SIVA-1 interaction with PCBP1 serves as a predictive biomarker for cisplatin sensitivity in gastric cancer and its inhibitory effect on tumor growth in vivo[J]. J Cancer,2024,15(13):4301-4312. doi:10.7150/jca.92963
[19] LIU R Q, WU Y T, CHENG Y,et al.TBBPA induced hepatocyte ferroptosis by PCBP1-mediated ferritinophagy[J]. J Hazard Mater,2025,494:138515. doi:10.1016/j.jhazmat.2025.138515
[20] JAIN C, SHAH Y M. PCBP1 is essential for proper iron absorption[J]. Blood, 2023,142(19):1585-1587. doi:10.1182/blood.2023022267
[21] PENG K, CHEN X, LIN A,et al. PolyC-RNA-binding protein 1 (PCBP1) enhances tropomyosin 3 (TPM3) mRNA stability to promote the progression of esophageal squamous cell carcinoma[J]. Bioengineered,2022,13(4):8581-8592. doi:10.1080/21655979.2022.2053801
[22] MEI W, WEI M, TANG C,et al. BCAT2 binding to PCBP1 regulates the PI3K/AKT signaling pathway to inhibit autophagy-related apoptosis and ferroptosis in prostate cancer[J]. Cell Death Dis,2025,16(1):337. doi:10.1038/s41419-025-07559-3
[23] JIANG Y, ZHOU H Z, ZHANG J X,et al. LINC00926, Regulated by TCF12, Modulates the Ubiquitination of GPX4 to Regulate Ferroptosis by Interacting with STUB1 in HUVECs[J].Mol Biotechnol,2025,doi: 10.1007/s12033-025-01441-5 .
[24] ZHANG X, ZHANG Y, LI R,et al. STUB1-mediated ubiquitination and degradation of NSUN2 promotes hepatocyte ferroptosis by decreasing m5C methylation of Gpx4 mRNA[J]. Cell Rep,2024,43(11):114885. doi:10.1016/j.celrep.2024.114885
[25] TIELIWAERDI A, AINI A, AMUTI M,et al. STUB1 promotes the degradation of HSPB1 and induces ferroptosis in lung cancer cells[J]. Environ Toxicol,2024,39(8):4156-4170. doi:10.1002/tox.24296
[26] SUN X, ZHANG Q, LIN X,et al. Imatinib induces ferroptosis in gastrointestinal stromal tumors by promoting STUB1-mediated GPX4 ubiquitination[J]. Cell Death Dis,2023,14(12):839. doi:10.1038/s41419-023-06300-2
[27] ZHANG L, LI Q, XU J,et al. Cimetidine promotes STUB1-mediated degradation of tumoral FOXP3 by activating PI3K-Akt pathway in gastric cancer[J]. Ann Transl Med,2020,8(20):1304. doi:10.21037/atm-20-6070
[28] DAI H, CHEN H, XU J,et al.The ubiquitin ligase CHIP modulates cellular behaviors of gastric cancer cells by regulating TRAF2[J].Cancer Cell Int,2019,19:132. doi:10.1186/s12935-019-0832-z
Outlines

/