Abnormal expression of glypican-3 and ubiquitin D in hepatocellular carcinoma and the associated interaction#br#

TAN Yu-jing DAI Zi-wei TANG Biao

Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (5) : 744-750.

PDF(7538 KB)
Welcome to visit Acta Anatomica Sinica! Today is Chinese
PDF(7538 KB)
Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (5) : 744-750. DOI: 10.16098/j.issn.0529-1356.2021.05.011
Cancer Biology

Abnormal expression of glypican-3 and ubiquitin D in hepatocellular carcinoma and the associated interaction#br#

  • TAN Yu-jing1  DAI Zi-wei2  TANG Biao2*#br#
Author information +
History +

Abstract

Objective  To explore the abnormal expression of ubiquitin D(UBD) and glypican-3(GPC3) among patients of hepatocellular carcinoma(HCC) by using analysis tools of genomics and epigenetics, so as to study their prognostic effects.    Methods  The online tools called ULCAN(http://ualan.path.uab.edu) and Gene Expression Profiling Interative Analysis(GEPIA) were used to perform expression analysis in genomics and epigenetics of UBD and GPC3. Moreover, GEPIA was conducted to evaluate the survival effects on HCC patients. The GeneCards was used to find the localization of UBD and GPC3 in tumor tissue and normal tissue. The STRING was utilized to perform the construction of PPI network and gene annotation. The correlation between UBD and GPC3 in progress of HCC was revealed based on Pearson correlation coefficient.    Results  UBD and GPC3 were dramatically up-regulated in HCC tissues, with downregulation of methylation level. UBD was located in 6p22.1 with primary expression in the nucleus, while GPC3 was located in Xq26.2 with main expression in the plasma membrane, extracellular matrix, endoplasmic reticulum, lysosome and golgi apparatus. The enrichment analysis showed that, UBD was enriched in activities involving proteasome, such as post-translation protein modification, ubiquitination and deubiquitination. GPC3 was enriched in the biosynthetic and catabolic process of glycosaminoglycan, possessed relationship with proteoglycans in cancer, ECM-receptor interaction, cell adhesion molecules (CAMs). Both of UBD and GPC3 were shown to exhibit a positive linear correlation, which suggested that GPC3 and UBD mediated the pathological process of HCC in cooperation. The survival analysis showed that, GPC3 exhibited a critical effect on survival of HCC patients.    Conclusion  UBD and GPC3 represent up-regulation in tumor tissue, in which GPC3 possesses a greater impact on the prognosis of HCC. GPC3 could be potential to serve as a practical biomarker for early diagnosis and medical intervention.

Key words

Hepatocellular carcinoma / Bioinformatics / Ubiqitin D / Glypican-3 / GEPIA database / Human

Cite this article

Download Citations
TAN Yu-jing DAI Zi-wei TANG Biao. Abnormal expression of glypican-3 and ubiquitin D in hepatocellular carcinoma and the associated interaction#br#[J]. Acta Anatomica Sinica. 2021, 52(5): 744-750 https://doi.org/10.16098/j.issn.0529-1356.2021.05.011

References

[1] Tang A, Hallouch O, Chernyak Ⅴ, et al. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis[J]. Abdom Radiol (NY), 2018, 43(1):13-25. 
[2] Akk?z H. Hepatocellular carcinoma: from molecular basis to novel treatment approaches[J]. Can J Gastroenterol Hepatol, 2019, 2019:4970731. 
[3] Lin DC, Mayakonda A, Dinh HQ, et al. Genomic and epigenomic heterogeneity of hepatocellular carcinoma[J]. Cancer Res, 2017, 77(9):2255-2265. 
[4] Lee SM, Kim-Ha J, Choi WY, et al. Interplay of genetic and epigenetic alterations in hepatocellular carcinoma[J]. Epigenomics, 2016, 8(7):993-1005. 
[5] Rongrui L, Na H, Zongfang L, et al. Epigenetic mechanism involved in the HBV/HCV-related hepatocellular carcinoma tumorigenesis[J]. Curr Pharm Des, 2014, 20(11):1715-1725. 
[6] Yu M, Luo H, Fan M, et al. Development of GPC3-specific chimeric antigen receptor-engineered natural killer cells for the treatment of hepatocellular carcinoma[J]. Mol Ther, 2018, 26(2):366-378.
[7] Cartier F, Indersie E, Lesjean S, et al. New tumor suppressor microRNAs target glypican-3 in human liver cancer[J]. Oncotarget, 2017, 8(25):41211-41226. 
[8] Shimizu Y, Suzuki T, Yoshikawa T, et al. Nextgeneration cancer immunotherapy targeting glypican-3[J]. Front Oncol, 2019, 9:248. 
[9] Nishida T, Kataoka H. Glypican 3-targeted therapy in hepatocellular carcinoma[J]. Cancers (Basel), 2019, 11(9):1339. 
[10] Arendt BM, Teterina A, Pettinelli P, et al. Cancer-related gene expression is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease[J]. Nutrition, 2019, 62:100-107. 
[11] Aichem A, Groettrup M. The ubiquitin-like modifier FAT10 in cancer development[J]. Int J Biochem Cell Biol, 2016, 79:451-461. 
[12] Hernández M, Quijada NM, Rodríguez-Lázaro D, et al. Bioinformatics of next generation sequencing in clinical microbiology diagnosis [J]. Rev Argent Microbiol, 2020, 52(2):150-161.
[13] Keerthikumar S. An introduction to proteome bioinformatics [J]. Methods Mol Biol, 2017, 1549: 1-3.
[14] Li N, Gao W, Zhang YF, et al. Glypicans as cancer therapeutic targets[J]. Trends Cancer, 2018, 4(11):741-754.
[15] French SW, Bardag-Gorce F, French BA, et al. The role of innate immunity in the pathogenesis of preneoplasia in drug-induced chronic hepatitis based on a mouse model[J]. Exp Mol Pathol, 2011, 91(3):653-659. 
[16] Filmus J, Capurro M, Rast J. Glypicans[J]. Genome Biol, 2008, 9(5):224. 
[17] Wu M, Liu Z, Zhang A, et al. Associated measurement of fucosylated levels of AFP, DCP, and GPC3 for early diagnosis in hepatocellular carcinoma[J]. Int J Biol Markers, 2019, 34(1):20-26.
[18] Sun B, Huang Z, Wang B, et al. Significance of glypican-3 (GPC3) expression in hepatocellular cancer diagnosis[J]. Med Sci Monit, 2017, 23:850-855. 
[19] Oliva J, Bardag-Gorce F, French BA, et al. Independent phenotype of binuclear hepatocytes and cellular localization of UbD[J]. Exp Mol Pathol, 2010, 89(2):103-108.
[20] Cui J, Chen Y, Wang HY, et al. Mechanisms and pathways of innate immune activation and regulation in health and cancer[J]. Hum Vaccin Immunother, 2014, 10(11):3270-3285.
PDF(7538 KB)

Accesses

Citation

Detail

Sections
Recommended

/