Skip to main content

Advertisement

SpringerLink
Log in

DAZAP1 overexpression promotes growth of HCC cell lines: a primary study using CEUS

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Hepatocellular carcinoma (HCC) is one of the most common types of hepatic carcinoma. The overall prognosis is poor. DAZAP1, a regulator of alternative splicing (AS) events, may participate in tumor growth.

Methods

We collected 105 HCC patients and tissue samples from the Department of Hepatological Surgery in the Second Affiliated Hospital of Qiqihar Medical University. TCGA datasets were downloaded and operated using the R project. DAZAP1 expressions were examined by quantitative RT-PCR and western blotting. CCK8 assay was used to investigate the cell proliferation, and transwell assay was employed to examine the ability of migration and invasion in vitro. Contrast-enhanced ultrasound (CEUS) was used to evaluate images and parameters of the tumor.

Results

DAZAP1 is highly expressed in the tissue samples of HCC. The peak intensity (PI) and area under the curve (AUC) of the tumor is higher than that of liver parenchyma, and correlated with high DAZAP1 expression. Parameters of CEUS in the tumor are correlated with TNM stage, tumor size, and vascularity. High DAZAP1 expression correlates with a shorter survival time and advanced histologic grade (G3–G4). Bioinformatical analysis revealed that downregulation of DAZAP1 identified differentiated expressed genes (DEGs) involved in the tumor growth process.

Conclusions

DAZAP1 is highly expressed in hepatic carcinoma and related to the blood flow, and high DAZAP1 expression predicts poor prognosis. DAZAP1 may promote liver carcinoma cell proliferation, migration, and invasion of HEPG2 cells. CEUS parameters are related to the high DAZAP1 expression, and will help to differentiate the HCC tumor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Vogel A, Cervantes A, Chau I, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:871–3.

    Article  Google Scholar 

  2. European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.

    Article  Google Scholar 

  3. Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63:844–55.

    Article  CAS  Google Scholar 

  4. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589–604.

    Article  Google Scholar 

  5. Lucatelli P, De Rubeis G, Basilico F, Ginanni Corradini L, Corona M, Bezzi M, Catalano C. Sequential dual-phase cone-beam CT is able to intra-procedurally predict the one-month treatment outcome of multi-focal HCC, in course of degradable starch microsphere TACE. Radiol Med. 2019;124:1212–9.

    Article  Google Scholar 

  6. Sasaki K, Ono M, Takabe K, Suzuki A, Kurihara Y. Specific intron-dependent loading of DAZAP1 onto the cox6c transcript suppresses pre-mRNA splicing efficacy and induces cell growth retardation. Gene. 2018;657:1–8.

    Article  CAS  Google Scholar 

  7. Smith RW, Anderson RC, Smith JW, Brook M, Richardson WA, Gray NK. DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation. RNA. 2011;17:1282–95.

    Article  CAS  Google Scholar 

  8. Byfield MP, Murray JT, Backer JM. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem. 2005;280:33076–82.

    Article  CAS  Google Scholar 

  9. Choudhury R, Roy SG, Tsai YS, Tripathy A, Graves LM, Wang Z. The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration. Nat Commun. 2014;5:3078.

    Article  Google Scholar 

  10. Yu M, Hong W, Ruan S, Guan R, Tu L, Huang B, Hou B, Jian Z, Ma L, Jin H. Genome-wide profiling of prognostic alternative splicing pattern in pancreatic cancer. Front Oncol. 2019;9:773.

    Article  Google Scholar 

  11. Chen T, Zheng W, Chen J, Lin S, Zou Z, Li X, Tan Z. Systematic analysis of survival-associated alternative splicing signatures in clear cell renal cell carcinoma. J Cell Biochem. 2020;121:4074–84.

    Article  CAS  Google Scholar 

  12. Huang H, Zheng J, Shen N, Wang G, Zhou G, Fang Y, Lin J, Zhao J. Identification of pathways and genes associated with synovitis in osteoarthritis using bioinformatics analyses. Sci Rep. 2018;8:10050.

    Article  Google Scholar 

  13. Papatheodoridis GV, Sypsa V, Dalekos GN, et al. Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B. J Hepatol. 2020;72:1088–96.

    Article  CAS  Google Scholar 

  14. Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61:191–9.

    Article  Google Scholar 

  15. Lv Y, Xu A, Wang N, et al. Retrospective study of TACE in the treatment of lobaplatin-induced thrombocytopenia in primary hepatocellular carcinoma. J BUON. 2019;24:2385–93.

    PubMed  Google Scholar 

  16. Zhang Y, Mao X, Chen W, et al. A discovery of clinically approved formula FBRP for repositioning to treat HCC by inhibiting PI3K/AKT/NF-κB activation. Mol Ther Nucleic Acids. 2020;19:890–904.

    Article  CAS  Google Scholar 

  17. Goina E, Skoko N, Pagani F. Binding of DAZAP1 and hnRNPA1/A2 to an exonic splicing silencer in a natural BRCA1 exon 18 mutant. Mol Cell Biol. 2008;28:3850–60.

    Article  CAS  Google Scholar 

  18. Prima V, Gore L, Caires A, Boomer T, Yoshinari M, Imaizumi M, Varella-Garcia M, Hunger SP. Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia. Leukemia. 2005;19:806–13.

    Article  CAS  Google Scholar 

  19. Prima V, Hunger SP. Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia. Leukemia. 2007;21:2470–5.

    Article  CAS  Google Scholar 

  20. Gu Z, Churchman M, Roberts K, et al. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia. Nat Commun. 2016;7:13331.

    Article  CAS  Google Scholar 

  21. Wang Q, Guo Y, Wang W, et al. RNA binding protein DAZAP1 promotes HCC progression and regulates ferroptosis by interacting with SLC7A11 mRNA. Exp Cell Res. 2021;399: 112453.

    Article  CAS  Google Scholar 

  22. Li J, Wang Y, Rao X, Wang Y, Feng W, Liang H, Liu Y. Roles of alternative splicing in modulating transcriptional regulation. BMC Syst Biol. 2017;11:89.

    Article  Google Scholar 

  23. Siam A, Baker M, Amit L, et al. Regulation of alternative splicing by p300-mediated acetylation of splicing factors. RNA. 2019;25:813–24.

    Article  CAS  Google Scholar 

  24. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet. 2008;40:1413–5.

    Article  CAS  Google Scholar 

  25. Sugnet CW, Kent WJ, Ares M Jr, Haussler D. Transcriptome and genome conservation of alternative splicing events in humans and mice. Pac Symp Biocomput. 2004;2004:66–77.

    Google Scholar 

  26. Li J, Yu P. Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis. Sci Rep. 2018;8:4124.

    Article  Google Scholar 

  27. Lee JS, Lin YY, Wang TS, Liu JY, Lin WW, Yang JJ. Antitumorigenic effects of ZAKβ, an alternative splicing isoform of ZAK. Chin J Physiol. 2018;61:25–34.

    Article  CAS  Google Scholar 

  28. Yuan JH, Liu XN, Wang TT, Pan W, Tao QF, Zhou WP, Wang F, Sun SH. The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1. Nat Cell Biol. 2017;19:820–32.

    Article  CAS  Google Scholar 

Download references

Funding

This study is funded by Qiqihar Science and Technology Bureau (SFZD-2019154).

Author information

Authors and Affiliations

  1. Department of Ultrasound, The Second Affiliated Hospital of Qiqihar Medical University, No. 37 Zhonghua Xi Road, Jianhua District, Qiqihar, 161000, China

    J. J. Deng & Y. Wang

  2. Department of General Surgery, The First Hospital of Qiqihar, Qiqihar, 161000, China

    G. P. Li, W. Lu & Z. Yan

Authors
  1. J. J. Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. P. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Z. Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JD and GL conceived and designed the study, and drafted the manuscript. JD, WL, ZY and YW collected, analyzed and interpreted the experimental data. JD and WL revised the manuscript for important intellectual content. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to J. J. Deng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by Ethical Committee of The Second Affiliated Hospital of Qiqihar Medical University and conducted in accordance with the ethical standards.

Informed consent

Yes.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 9 KB)

Supplementary file2 (DOCX 14 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, J.J., Li, G.P., Lu, W. et al. DAZAP1 overexpression promotes growth of HCC cell lines: a primary study using CEUS. Clin Transl Oncol 24, 1168–1176 (2022). https://doi.org/10.1007/s12094-021-02758-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-021-02758-8

Keywords

Search

Navigation