Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
November-2024 Volume 21 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2024 Volume 21 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)

  • Authors:
    • Lei Yang
    • Zhipeng Sun
  • View Affiliations / Copyright

    Affiliations: Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 82
    |
    Published online on: September 6, 2024
       https://doi.org/10.3892/mco.2024.2780
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

In recent years, the incidence of liver cancer has increased annually. However, current medical treatments for liver cancer are limited, and most patients have a high risk of recurrence after surgery. Therefore, the discovery and development of novel treatment targets for liver cancer is urgently needed. Apurinic/apyrimidinic endonuclease 1 (APE1) is a protein that has a DNA repair function and serves an important role in various physiological processes, including reduction‑oxidation, cell proliferation and differentiation. The expression levels of APE1 are abnormally elevated in liver cancer cells, as ectopic expression of the APE1 gene has been reported, in addition to other abnormal signs, such as cell proliferation and migration. Therefore, it could be suggested that APE1 is an important indicator of hepatocellular carcinogenesis. APE1 may be used as a therapeutic target for tumors and proposed targeted therapy against abnormal APE1 expression could potentially inhibit the progression of tumors. The present review aimed to introduce the important role of APE1 in the physiological processes of tumor cells and the feasibility of using APE1 as a potential therapeutic target, providing a novel direction for the clinical treatment of liver cancer.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021.PubMed/NCBI View Article : Google Scholar

2 

Singal AG, Kanwal F and Llovet JM: Global trends in hepatocellular carcinoma epidemiology: Implications for screening, prevention and therapy. Nat Rev Clin Oncol. 20:864–884. 2023.PubMed/NCBI View Article : Google Scholar

3 

Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A and Roberts LR: A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 16:589–604. 2019.PubMed/NCBI View Article : Google Scholar

4 

Clark T, Maximin S, Meier J, Pokharel S and Bhargava P: Hepatocellular carcinoma: Review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Curr Probl Diagn Radiol. 44:479–486. 2015.PubMed/NCBI View Article : Google Scholar

5 

Sia D, Villanueva A, Friedman SL and Llovet JM: Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology. 152:745–761. 2017.PubMed/NCBI View Article : Google Scholar

6 

Zhang H, Su X, Burley SK and Zheng XFS: mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma. Theranostics. 12:3518–3533. 2022.PubMed/NCBI View Article : Google Scholar

7 

Vogel A, Meyer T, Sapisochin G, Salem R and Saborowski A: Hepatocellular carcinoma. Lancet. 400:1345–1362. 2022.PubMed/NCBI View Article : Google Scholar

8 

Chang Y, Jeong SW, Young Jang J and Jae Kim Y: Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma. Int J Mol Sci. 21(8165)2020.PubMed/NCBI View Article : Google Scholar

9 

Galle PP, Dufour JF, Peck-Radosavljevic M, Trojan J and Vogel A: Systemic therapy of advanced hepatocellular carcinoma. Future Oncol. 17:1237–1251. 2021.PubMed/NCBI View Article : Google Scholar

10 

Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T and Lencioni R: Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 18:293–313. 2021.PubMed/NCBI View Article : Google Scholar

11 

Llovet JM, Montal R, Sia D and Finn RS: Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 15:599–616. 2018.PubMed/NCBI View Article : Google Scholar

12 

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009.PubMed/NCBI View Article : Google Scholar

13 

Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX and Finn RS: Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 19:151–172. 2022.PubMed/NCBI View Article : Google Scholar

14 

Kong FH, Ye QF, Miao XY, Liu X, Huang SQ, Xiong L, Wen Y and Zhang ZJ: Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma. Theranostics. 11:5464–5490. 2021.PubMed/NCBI View Article : Google Scholar

15 

Ladd AD, Duarte S, Sahin I and Zarrinpar A: Mechanisms of drug resistance in HCC. Hepatology. 79:926–940. 2024.PubMed/NCBI View Article : Google Scholar

16 

Dattachoudhury S, Sharma R, Kumar A and Jaganathan BG: Sorafenib inhibits proliferation, migration and invasion of breast cancer cells. Oncology. 98:478–486. 2020.PubMed/NCBI View Article : Google Scholar

17 

Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, Wang Q, Wang S, Rong D, Reiter FP, et al: The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 5(87)2020.PubMed/NCBI View Article : Google Scholar

18 

Tian C, Liu Y, Xue L, Zhang D, Zhang X, Su J, Chen J, Li X, Wang L and Jiao S: Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial-mesenchymal transition. Open Life Sci. 17:616–625. 2022.PubMed/NCBI View Article : Google Scholar

19 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008.PubMed/NCBI View Article : Google Scholar

20 

Gupta N, Verma RK, Prinja S and Dhiman RK: Cost-effectiveness of sorafenib for treatment of advanced hepatocellular carcinoma in India. J Clin Exp Hepatol. 9:468–475. 2019.PubMed/NCBI View Article : Google Scholar

21 

Zschäbitz S and Grüllich C: Lenvantinib: A tyrosine kinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRα, KIT and RET. Recent Results Cancer Res. 211:187–198. 2018.PubMed/NCBI View Article : Google Scholar

22 

Bo W and Chen Y: Lenvatinib resistance mechanism and potential ways to conquer. Front Pharmacol. 14(1153991)2023.PubMed/NCBI View Article : Google Scholar

23 

Liu X, Lu Y and Qin S: Atezolizumab and bevacizumab for hepatocellular carcinoma: Mechanism, pharmacokinetics and future treatment strategies. Future Oncol. 17:2243–2256. 2021.PubMed/NCBI View Article : Google Scholar

24 

Gao X, Zhao R, Ma H and Zuo S: Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: A single-arm meta-analysis. BMC Cancer. 23(635)2023.PubMed/NCBI View Article : Google Scholar

25 

López DJ, Rodríguez JA and Bañuelos S: Molecular mechanisms regulating the DNA repair protein APE1: A focus on its flexible N-terminal tail domain. Int J Mol Sci. 22(6308)2021.PubMed/NCBI View Article : Google Scholar

26 

Caston RA, Gampala S, Armstrong L, Messmann RA, Fishel ML and Kelley MR: The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease. Drug Discov Today. 26:218–228. 2021.PubMed/NCBI View Article : Google Scholar

27 

He H, Liu X, Wu Y, Qi L, Huang J, Zhou Y, Zeng J, Wang K and He X: DNA nanotechnology-empowered fluorescence imaging of APE1 Activity. Chemistry. 5:1815–1831. 2023.

28 

An SY, Jin SA, Seo HJ, Lee YR, Kim S, Jeon BH and Jeong JO: Protective effect of secretory APE1/Ref-1 on doxorubicin-induced cardiotoxicity via suppression of ROS and p53 pathway. ESC Heart Fail. 11:1182–1193. 2024.PubMed/NCBI View Article : Google Scholar

29 

Zhang S, He L, Dai N, Guan W, Shan J, Yang X, Zhong Z, Qing Y, Jin F, Chen C, et al: Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients. Oncotarget. 7:77482–77494. 2016.PubMed/NCBI View Article : Google Scholar

30 

McIlwain DW, Fishel ML, Boos A, Kelley MR and Jerde TJ: APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells. Oncotarget. 9:10962–10977. 2018.PubMed/NCBI View Article : Google Scholar

31 

Lee YR, Park MS, Joo HK, Kim KM, Kim J, Jeon BH and Choi S: Therapeutic positioning of secretory acetylated APE1/Ref-1 requirement for suppression of tumor growth in triple-negative breast cancer in vivo. Sci Rep. 8(8701)2018.PubMed/NCBI View Article : Google Scholar

32 

Di Maso V, Mediavilla MG, Vascotto C, Lupo F, Baccarani U, Avellini C, Tell G, Tiribelli C and Crocè LS: Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis. PLoS One. 10(e0143289)2015.PubMed/NCBI View Article : Google Scholar

33 

Logsdon DP, Grimard M, Luo M, Shahda S, Jiang Y, Tong Y, Yu Z, Zyromski N, Schipani E, Carta F, et al: Regulation of HIF1α under Hypoxia by APE1/Ref-1 Impacts CA9 expression: Dual targeting in patient-derived 3D pancreatic cancer models. Mol Cancer Ther. 15:2722–2732. 2016.PubMed/NCBI View Article : Google Scholar

34 

Sun Z, Zhu Y, Aminbuhe Fan Q, Peng J and Zhang N: Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells. Biosci Trends. 12:456–462. 2018.PubMed/NCBI View Article : Google Scholar

35 

Lu X, Zhao H, Yuan H, Chu Y and Zhu X: High nuclear expression of APE1 correlates with unfavorable prognosis and promotes tumor growth in hepatocellular carcinoma. J Mol Histol. 52:219–231. 2021.PubMed/NCBI View Article : Google Scholar

36 

Di Maso V, Avellini C, Crocè LS, Rosso N, Quadrifoglio F, Cesaratto L, Codarin E, Bedogni G, Beltrami CA, Tell G and Tiribelli C: Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: Possible prognostic significance. Mol Med. 13:89–96. 2007.PubMed/NCBI View Article : Google Scholar

37 

Hegde ML, Hazra TK and Mitra S: Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res. 18:27–47. 2008.PubMed/NCBI View Article : Google Scholar

38 

Demple B, Herman T and Chen DS: Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: Definition of a family of DNA repair enzymes. Proc Natl Acad Sci U S A. 88:11450–11454. 1991.PubMed/NCBI View Article : Google Scholar

39 

Kciuk M, Marciniak B, Mojzych M and Kontek R: Focus on UV-Induced DNA damage and repair-disease relevance and protective strategies. Int J Mol Sci. 21(7264)2020.PubMed/NCBI View Article : Google Scholar

40 

Krokan HE and Bjørås M: Base excision repair. Cold Spring Harb Perspect Biol. 5(a012583)2013.PubMed/NCBI View Article : Google Scholar

41 

Hindi NN, Elsakrmy N and Ramotar D: The base excision repair process: Comparison between higher and lower eukaryotes. Cell Mol Life Sci. 78:7943–7965. 2021.PubMed/NCBI View Article : Google Scholar

42 

Khodyreva SN, Prasad R, Ilina ES, Sukhanova MV, Kutuzov MM, Liu Y, Hou EW, Wilson SH and Lavrik OI: Apurinic/apyrimidinic (AP) site recognition by the 5'-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1). Proc Natl Acad Sci USA. 107:22090–22095. 2010.PubMed/NCBI View Article : Google Scholar

43 

Vidal AE, Boiteux S, Hickson ID and Radicella JP: XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J. 20(6530-6539-6539)2001.PubMed/NCBI View Article : Google Scholar

44 

Bennett RA, Wilson DM III, Wong D and Demple B: Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc Natl Acad Sci USA. 94:7166–7169. 1997.PubMed/NCBI View Article : Google Scholar

45 

Antoniali G, Serra F, Lirussi L, Tanaka M, D'Ambrosio C, Zhang S, Radovic S, Dalla E, Ciani Y, Scaloni A, et al: Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nat Commun. 8(797)2017.PubMed/NCBI View Article : Google Scholar

46 

Berquist BR, McNeill DR and Wilson DM III: Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision. J Mol Biol. 379:17–27. 2008.PubMed/NCBI View Article : Google Scholar

47 

Antoniali G, Dalla E, Mangiapane G, Zhao X, Jing X, Cheng Y, De Sanctis V, Ayyildiz D, Piazza S, Li M and Tell G: APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b. Cell Mol Life Sci. 79(446)2022.PubMed/NCBI View Article : Google Scholar

48 

Malfatti MC, Antoniali G, Codrich M and Tell G: Coping with RNA damage with a focus on APE1, a BER enzyme at the crossroad between DNA damage repair and RNA processing/decay. DNA Repair (Amst). 104(103133)2021.PubMed/NCBI View Article : Google Scholar

49 

Kladova OA, Bazlekowa-Karaban M, Baconnais S, Piétrement O, Ishchenko AA, Matkarimov BT, Iakovlev DA, Vasenko A, Fedorova OS, Le Cam E, et al: The role of the N-terminal domain of human apurinic/apyrimidinic endonuclease 1, APE1, in DNA glycosylase stimulation. DNA Repair (Amst). 64:10–25. 2018.PubMed/NCBI View Article : Google Scholar

50 

Oliveira TT, Coutinho LG, de Oliveira LOA, Timoteo ARS, Farias GC and Agnez-Lima LF: APE1/Ref-1 role in inflammation and immune response. Front Immunol. 13(793096)2022.PubMed/NCBI View Article : Google Scholar

51 

Hu Z, Hui B, Hou X, Liu R, Sukhanov S and Liu X: APE1 inhibits foam cell formation from macrophages via LOX1 suppression. Am J Transl Res. 12:6559–6568. 2020.PubMed/NCBI

52 

Luo M, Zhang J, He H, Su D, Chen Q, Gross ML, Kelley MR and Georgiadis MM: Characterization of the Redox activity and disulfide bond formation in apurinic/apyrimidinic endonuclease. Biochemistry. 51:695–705. 2012.PubMed/NCBI View Article : Google Scholar

53 

Pekhale K, Haval G, Perween N, Antoniali G, Tell G and Ghaskadbi S and Ghaskadbi S: DNA repair enzyme APE1 from evolutionarily ancient Hydra reveals redox activity exclusively found in mammalian APE1. DNA Repair (Amst). 59:44–56. 2017.PubMed/NCBI View Article : Google Scholar

54 

Kelley MR, Logsdon D and Fishel ML: Targeting DNA repair pathways for cancer treatment: What's new? Future Oncol. 10:1215–1237. 2014.PubMed/NCBI View Article : Google Scholar

55 

Kelley MR, Georgiadis MM and Fishel ML: APE1/Ref-1 role in redox signaling: Translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol. 5:36–53. 2012.PubMed/NCBI View Article : Google Scholar

56 

Georgiadis MM, Luo M, Gaur RK, Delaplane S, Li X and Kelley MR: Evolution of the redox function in mammalian Apurinic/apyrimidinic endonuclease. Mutat Res. 643:54–63. 2008.PubMed/NCBI View Article : Google Scholar

57 

Lee EO, Joo HK, Lee YR, Kim S, Lee KH, Lee SD and Jeon BH: APE1/Ref-1 inhibits adipogenic transcription factors during adipocyte differentiation in 3T3-L1 cells. Int J Mol Sci. 24(3251)2023.PubMed/NCBI View Article : Google Scholar

58 

Shah F, Logsdon D, Messmann RA, Fehrenbacher JC, Fishel ML and Kelley MR: Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: From bench to clinic. NPJ Precis Oncol. 1(19)2017.PubMed/NCBI View Article : Google Scholar

59 

Garcia-Bailo B, El-Sohemy A, Haddad PS, Arora P, Benzaied F, Karmali M and Badawi A: Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: Modulation of inflammation and oxidative stress. Biologics. 5:7–19. 2011.PubMed/NCBI View Article : Google Scholar

60 

Biswas A, Khanna S, Roy S, Pan X, Sen CK and Gordillo GM: Endothelial cell tumor growth is Ape/ref-1 dependent. Am J Physiol Cell Physiol. 309:C296–C307. 2015.PubMed/NCBI View Article : Google Scholar

61 

Ding J, Fishel ML, Reed AM, McAdams E, Czader MB, Cardoso AA and Kelley MR: Ref-1/APE1 as a transcriptional regulator and novel therapeutic target in pediatric T-cell Leukemia. Mol Cancer Ther. 16:1401–1411. 2017.PubMed/NCBI View Article : Google Scholar

62 

Fishel ML, Jiang Y, Rajeshkumar NV, Scandura G, Sinn AL, He Y, Shen C, Jones DR, Pollok KE, Ivan M, et al: Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth. Mol Cancer Ther. 10:1698–1708. 2011.PubMed/NCBI View Article : Google Scholar

63 

Vasko MR, Guo C, Thompson EL and Kelley MR: The repair function of the multifunctional DNA repair/redox protein APE1 is neuroprotective after ionizing radiation. DNA Repair (Amst). 10:942–952. 2011.PubMed/NCBI View Article : Google Scholar

64 

Zou GM and Maitra A: Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration. Mol Cancer Ther. 7:2012–2021. 2008.PubMed/NCBI View Article : Google Scholar

65 

Huynh J, Chand A, Gough D and Ernst M: Therapeutically exploiting STAT3 activity in cancer-using tissue repair as a road map. Nat Rev Cancer. 19:82–96. 2019.PubMed/NCBI View Article : Google Scholar

66 

Hu X, li J, Fu M, Zhao X and Wang W: The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct Target Ther. 6(402)2021.PubMed/NCBI View Article : Google Scholar

67 

Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G and Bahar M: The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 15(23)2017.PubMed/NCBI View Article : Google Scholar

68 

Cardoso AA, Jiang Y, Luo M, Reed AM, Shahda S, He Y, Maitra A, Kelley MR and Fishel ML: APE1/Ref-1 regulates STAT3 transcriptional activity and APE1/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival. PLoS One. 7(e47462)2012.PubMed/NCBI View Article : Google Scholar

69 

Fishel ML, Xia H, McGeown J, McIlwain DW, Elbanna M, Craft AA, Kaimakliotis HZ, Sandusky GE, Zhang C, Pili R, et al: Antitumor activity and mechanistic characterization of APE1/Ref-1 inhibitors in bladder cancer. Mol Cancer Ther. 18:1947–1960. 2019.PubMed/NCBI View Article : Google Scholar

70 

Pawlus MR, Wang L and Hu CJ: STAT3 and HIF1α cooperatively activate HIF1 target genes in MDA-MB-231 and RCC4 cells. Oncogene. 33:1670–1679. 2014.PubMed/NCBI View Article : Google Scholar

71 

Dinarello A, Betto RM, Diamante L, Tesoriere A, Ghirardo R, Cioccarelli C, Meneghetti G, Peron M, Laquatra C, Tiso N, et al: STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia. Cell Death Discov. 9(226)2023.PubMed/NCBI View Article : Google Scholar

72 

Rad E, Dodd K, Thomas L, Upadhyaya M and Tee A: STAT3 and HIF1α signaling drives oncogenic cellular phenotypes in malignant peripheral nerve sheath tumors. Mol Cancer Res. 13:1149–1160. 2015.PubMed/NCBI View Article : Google Scholar

73 

Bhakat KK, Mantha AK and Mitra S: Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein. Antioxid Redox Signal. 11:621–638. 2009.PubMed/NCBI View Article : Google Scholar

74 

Wu HH, Cheng YW, Chang JT, Wu TC, Liu WS, Chen CY and Lee H: Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-kappaB activation. Oncogene. 29:4330–4340. 2010.PubMed/NCBI View Article : Google Scholar

75 

Huang TT, Wuerzberger-Davis SM, Wu ZH and Miyamoto S: Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell. 115:565–576. 2003.PubMed/NCBI View Article : Google Scholar

76 

Xia L, Tan S, Zhou Y, Lin J, Wang H, Oyang L, Tian Y, Liu L, Su M, Wang H, et al: Role of the NFκB-signaling pathway in cancer. Onco Targets Ther. 11:2063–2073. 2018.PubMed/NCBI View Article : Google Scholar

77 

Siqueira PB, de Sousa Rodrigues MM, de Amorim ÍSS, da Silva TG, da Silva Oliveira M, Rodrigues JA, de Souza da Fonseca A and Mencalha AL: The APE1/REF-1 and the hallmarks of cancer. Mol Biol Rep. 51(47)2024.PubMed/NCBI View Article : Google Scholar

78 

Shin JH, Choi S, Lee YR, Park MS, Na YG, Irani K, Lee SD, Park JB, Kim JM, Lim JS and Jeon BH: APE1/Ref-1 as a serological biomarker for the detection of bladder cancer. Cancer Res Treat. 47:823–833. 2015.PubMed/NCBI View Article : Google Scholar

79 

Luo M and Kelley MR: Inhibition of the human apurinic/apyrimidinic endonuclease (APE1) repair activity and sensitization of breast cancer cells to DNA alkylating agents with lucanthone. Anticancer Res. 24:2127–2134. 2004.PubMed/NCBI

80 

Long K, Gu L, Li L, Zhang Z, Li E, Zhang Y, He L, Pan F, Guo Z and Hu Z: Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer. Cell Death Dis. 12(503)2021.PubMed/NCBI View Article : Google Scholar

81 

Fishel ML, He Y, Reed AM, Chin-Sinex H, Hutchins GD, Mendonca MS and Kelley MR: Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. DNA Repair (Amst). 7:177–186. 2008.PubMed/NCBI View Article : Google Scholar

82 

Deng X, Zhen P, Niu X, Dai Y, Wang Y and Zhou M: APE1 promotes proliferation and migration of cutaneous squamous cell carcinoma. J Dermatol Sci. 100:67–74. 2020.PubMed/NCBI View Article : Google Scholar

83 

Yang Z, Yang S, Misner BJ, Liu-Smith F and Meyskens FL: The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression. Int J Oncol. 45:1820–1828. 2014.PubMed/NCBI View Article : Google Scholar

84 

Singh AK, Kumar R and Pandey AK: Hepatocellular carcinoma: Causes, mechanism of progression and biomarkers. Curr Chem Genom Transl Med. 12:9–26. 2018.PubMed/NCBI View Article : Google Scholar

85 

Tell G, Quadrifoglio F, Tiribelli C and Kelley MR: The many functions of APE1/Ref-1: Not only a DNA repair enzyme. Antioxid Redox Signal. 11:601–620. 2009.PubMed/NCBI View Article : Google Scholar

86 

Sheng Q, Zhang Y, Wang R, Zhang J, Chen B, Wang J, Zhang W and Xin X: Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer. Med Oncol. 29:1265–1271. 2012.PubMed/NCBI View Article : Google Scholar

87 

Bazzani V, Barchiesi A, Radecka D, Pravisani R, Guadagno A, Di Loreto C, Baccarani U and Vascotto C: Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma. BMC Cancer. 20(969)2020.PubMed/NCBI View Article : Google Scholar

88 

Wu HH, Chu YC, Wang L, Tsai LH, Lee MC, Chen CY, Shieh SH, Cheng YW and Lee H: Cytoplasmic Ape1 Expression Elevated by p53 aberration may predict survival and relapse in resected non-small cell lung cancer. Ann Surg Oncol. 20 (Suppl 3):S336–S347. 2013.PubMed/NCBI View Article : Google Scholar

89 

Abbotts R and Madhusudan S: Human AP endonuclease 1 (APE1): From mechanistic insights to druggable target in cancer. Cancer Treat Rev. 36:425–435. 2010.PubMed/NCBI View Article : Google Scholar

90 

Malfatti MC, Bellina A, Antoniali G and Tell G: Revisiting two decades of research focused on targeting APE1 for cancer therapy: The pros and cons. Cells. 12(1895)2023.PubMed/NCBI View Article : Google Scholar

91 

Kumar S, Zhao J, Talluri S, Buon L, Mu S, Potluri LB, Liao C, Shi J, Chakraborty C, Gonzalez GB, et al: Elevated APE1 dysregulates homologous recombination and cell cycle driving genomic evolution, tumorigenesis, and chemoresistance in esophageal adenocarcinoma. Gastroenterology. 165:357–373. 2023.PubMed/NCBI View Article : Google Scholar

92 

Wang D, Xiang DB, Yang XQ, Chen LS, Li MX, Zhong ZY and Zhang YS: APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer. 66:298–304. 2009.PubMed/NCBI View Article : Google Scholar

93 

Franchi LP, de Freitas Lima JEB, Piva HL and Tedesco AC: The redox function of apurinic/apyrimidinic endonuclease 1 as key modulator in photodynamic therapy. J Photochem Photobiol B. 211(111992)2020.PubMed/NCBI View Article : Google Scholar

94 

Zhou J, Wei Z, Yang C, Jia D, Pan B, Zeng Y, Sun D and Yu Y: APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma. Transl Oncol. 36(101749)2023.PubMed/NCBI View Article : Google Scholar

95 

Li Y, Zhao X, Xiao H, Yang B, Liu J, Rao W, Dai X, Li M, Dai N, Yang Y and Wang D: APE1 may influence CD4+ naïve T cells on recurrence free survival in early stage NSCLC. BMC Cancer. 21(233)2021.PubMed/NCBI View Article : Google Scholar

96 

Woo J, Park H, Sung SH, Moon BI, Suh H and Lim W: Prognostic Value of Human Apurinic/Apyrimidinic Endonuclease 1 (APE1) Expression in Breast Cancer. PLoS One. 9(e99528)2014.PubMed/NCBI View Article : Google Scholar

97 

Lee SG, Lee DG, Joo YH and Chung N: Synergistic inhibitory effects of the oxyresveratrol and dacarbazine combination against melanoma cells. Oncol Lett. 22(667)2021.PubMed/NCBI View Article : Google Scholar

98 

Gómez-Zorita S, González-Arceo M, Fernández-Quintela A, Eseberri I, Trepiana J and Portillo MP: Scientific evidence supporting the beneficial effects of isoflavones on human health. Nutrients. 12(3853)2020.PubMed/NCBI View Article : Google Scholar

99 

Sui J, Li M, Qian C, Wang S, Cheng Y, Chen BP and Wang D: Functional analysis of tanshinone IIA that blocks the redox function of human apurinic/apyrimidinic endonuclease 1/redox factor-1. Drug Des Devel Ther. 8:2147–2160. 2014.PubMed/NCBI View Article : Google Scholar

100 

Cesaratto L, Codarin E, Vascotto C, Leonardi A, Kelley MR, Tiribelli C and Tell G: Specific inhibition of the redox activity of ape1/ref-1 by e3330 blocks tnf-α-induced activation of IL-8 production in liver cancer cell lines. PLoS One. 8(e70909)2013.PubMed/NCBI View Article : Google Scholar

101 

Kang S, Wang Z, Li B, Gao X, He W, Cao S, Cai Y and Chen H: Anti-tumor effects of resveratrol on malignant melanoma is associated with promoter demethylation of RUNX3 gene. Pharmazie. 74:163–167. 2019.PubMed/NCBI View Article : Google Scholar

102 

Laev SS, Salakhutdinov NF and Lavrik OI: Inhibitors of nuclease and redox activity of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1). Bioorg Med Chem. 25:2531–2544. 2017.PubMed/NCBI View Article : Google Scholar

103 

Kim IS: Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for humans. Antioxidants (Basel). 10(1064)2021.PubMed/NCBI View Article : Google Scholar

104 

Hillman GG: Soy isoflavones protect normal tissues while enhancing radiation responses. Semin Radiat Oncol. 29:62–71. 2019.PubMed/NCBI View Article : Google Scholar

105 

Singh-Gupta V, Joiner MC, Runyan L, Yunker CK, Sarkar FH, Miller S, Gadgeel SM, Konski AA and Hillman GG: Soy isoflavones augment radiation effect by inhibiting APE1/Ref-1 DNA repair activity in non-small cell lung cancer. J Thorac Oncol. 6:688–698. 2011.PubMed/NCBI View Article : Google Scholar

106 

Su D, Delaplane S, Luo M, Rempel DL, Vu B, Kelley MR, Gross ML and Georgiadis MM: Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: Evidence for an alternate conformation of the enzyme. Biochemistry. 50:82–92. 2011.PubMed/NCBI View Article : Google Scholar

107 

Luo M, Delaplane S, Jiang A, Reed A, He Y, Fishel M, Nyland RL II, Borch RF, Qiao X, Georgiadis MM and Kelley MR: Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: Small-molecule inhibition of the redox function of Ape1. Antioxid Redox Signal. 10:1853–1867. 2008.PubMed/NCBI View Article : Google Scholar

108 

Zou GM, Karikari C, Kabe Y, Handa H, Anders RA and Maitra A: The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: Therapeutic implications in tumor angiogenesis. J Cell Physiol. 219:209–218. 2009.PubMed/NCBI View Article : Google Scholar

109 

Sengupta S, Mantha AK, Mitra S and Bhakat KK: Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1. Oncogene. 30:482–493. 2011.PubMed/NCBI View Article : Google Scholar

110 

Du Y, Zhou Y, Yan X, Pan F, He L, Guo Z and Hu Z: APE1 inhibition enhances ferroptotic cell death and contributes to hepatocellular carcinoma therapy. Cell Death Differ. 31:431–446. 2024.PubMed/NCBI View Article : Google Scholar

111 

Sadek K, Abouzed T, Nasr S and Shoukry M: Licochalcone B ameliorates liver cancer via targeting of apoptotic genes, DNA repair systems, and cell cycle control. Iran J Pharm Res. 19:372–386. 2020.PubMed/NCBI View Article : Google Scholar

112 

Sadek K, Abouzeid T, Nasr S and Shukry M: Role and potential targeting of hepatic apurinic/apyrimidinic endonuclease-1 and cyclin-dependent kinase-4 in hepatocellular carcinoma. Can J Physiol Pharmacol. 96(X)2018.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang L and Sun Z: Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review). Mol Clin Oncol 21: 82, 2024.
APA
Yang, L., & Sun, Z. (2024). Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review). Molecular and Clinical Oncology, 21, 82. https://doi.org/10.3892/mco.2024.2780
MLA
Yang, L., Sun, Z."Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)". Molecular and Clinical Oncology 21.5 (2024): 82.
Chicago
Yang, L., Sun, Z."Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)". Molecular and Clinical Oncology 21, no. 5 (2024): 82. https://doi.org/10.3892/mco.2024.2780
Copy and paste a formatted citation
x
Spandidos Publications style
Yang L and Sun Z: Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review). Mol Clin Oncol 21: 82, 2024.
APA
Yang, L., & Sun, Z. (2024). Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review). Molecular and Clinical Oncology, 21, 82. https://doi.org/10.3892/mco.2024.2780
MLA
Yang, L., Sun, Z."Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)". Molecular and Clinical Oncology 21.5 (2024): 82.
Chicago
Yang, L., Sun, Z."Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)". Molecular and Clinical Oncology 21, no. 5 (2024): 82. https://doi.org/10.3892/mco.2024.2780
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team