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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2021 Volume 22 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-2021 Volume 22 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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression

Corrigendum in: /10.3892/ol.2022.13321
  • Authors:
    • Ruikai Li
    • Chenxiang He
    • Liangliang Shen
    • Shuai Wang
    • Yao Shen
    • Fan Feng
    • Jian Zhang
    • Jianyong Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Xijing Hospital, Xi'an, Shaanxi 710032, P.R. China, Department of General Surgery, Shanghai Fourth People's Hospital Affiliated to Tongji University of Medicine, Shanghai 200080, P.R. China, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 782
    |
    Published online on: September 13, 2021
       https://doi.org/10.3892/ol.2021.13043
  • 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

The incidence of colorectal cancer (CRC) has remained high in recent years, and 5‑fluorouracil (5‑FU) is a vital chemotherapeutic agent for its treatment. Our previous study reported that N‑myc downstream‑regulated gene 4 (NDRG4) plays a tumor‑suppressive role in CRC, but the mechanisms associated with NDRG4 and 5‑FU chemosensitivity remain unclear. The results of the present study demonstrate that NDRG4 sensitized CRC cells to 5‑FU by upregulating DNA damage inducible transcript 3 (DDIT3). NDRG4 inhibited the proliferation of CRC cells and the activation of PI3K/AKT and ERK signaling. Furthermore, NDRG4 promoted CRC cell apoptosis induced by 5‑FU. Mechanistic analyses revealed that NDRG4 upregulated DDIT3 expression, and that the proapoptotic effect of NDRG4 under 5‑FU treatment conditions was dependent on DDIT3. These findings support the biological value of the association between NDRG4, DDIT3 and 5‑FU chemosensitivity in CRC, and may advance the clinical treatment of CRC in the future.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

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. View Article : Google Scholar : PubMed/NCBI

2 

Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ and Watanabe T: Colorectal cancer. Nat Rev Dis Primers. 1:150652015. View Article : Google Scholar : PubMed/NCBI

3 

Xie YH, Chen YX and Fang JY: Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 5:222020. View Article : Google Scholar : PubMed/NCBI

4 

Brown KGM, Solomon MJ, Mahon K and O'Shannassy S: Management of colorectal cancer. BMJ. 366:l45612019. View Article : Google Scholar : PubMed/NCBI

5 

Vodenkova S, Buchler T, Cervena K, Veskrnova V, Vodicka P and Vymetalkova V: 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future. Pharmacol Ther. 206:1074472020. View Article : Google Scholar : PubMed/NCBI

6 

Xie P, Mo JL, Liu JH, Li X, Tan LM, Zhang W, Zhou HH and Liu ZQ: Pharmacogenomics of 5-fluorouracil in colorectal cancer: Review and update. Cell Oncol (Dordr). 43:989–1001. 2020. View Article : Google Scholar : PubMed/NCBI

7 

Yu C, Hao X, Zhang S, Hu W, Li J, Sun J and Zheng M: Characterization of the prognostic values of the NDRG family in gastric cancer. Therap Adv Gastroenterol. 12:17562848198585072019. View Article : Google Scholar : PubMed/NCBI

8 

Shi HH, Liu HE and Luo XJ: Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function. BMB Rep. 53:658–663. 2020. View Article : Google Scholar : PubMed/NCBI

9 

Cao L, Hu T, Lu H and Peng D: N-MYC downstream regulated gene 4 (NDRG4), a frequent downregulated gene through DNA hypermethylation, plays a tumor suppressive role in esophageal adenocarcinoma. Cancers (Basel). 12:25732020. View Article : Google Scholar : PubMed/NCBI

10 

Chen X, Yang Y, Liu J, Li B, Xu Y, Li C, Xu Q, Liu G, Chen Y, Ying J and Duan S: NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population. Oncotarget. 8:8105–8119. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Kadiyska T and Nossikoff A: Stool DNA methylation assays in colorectal cancer screening. World J Gastroenterol. 21:10057–10061. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Puthalakath H, O'Reilly LA, Gunn P, Lee L, Kelly PN, Huntington ND, Hughes PD, Michalak EM, McKimm-Breschkin J, Motoyama N, et al: ER stress triggers apoptosis by activating BH3-only protein Bim. Cell. 129:1337–1349. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Li L, Chen Q, Yu Y, Chen H, Lu M, Huang Y, Li P and Chang H: RKI-1447 suppresses colorectal carcinoma cell growth via disrupting cellular bioenergetics and mitochondrial dynamics. J Cell Physiol. 235:254–266. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Tan W, Liao Y, Qiu Y, Liu H, Tan D, Wu T, Tang M, Zhang S and Wang H: MiRNA 146a promotes chemotherapy resistance in lung cancer cells by targeting DNA damage inducible transcript 3 (CHOP). Cancer Lett. 428:55–68. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Cao Z, Liao Q, Su M, Huang K, Jin J and Cao D: AKT and ERK dual inhibitors: The way forward? Cancer Lett. 459:30–40. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Dekker E, Tanis PJ, Vleugels JLA, Kasi PM and Wallace MB: Colorectal cancer. Lancet. 394:1467–1480. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Stintzing S: Management of colorectal cancer. F1000Prime Rep. 6:1082014. View Article : Google Scholar : PubMed/NCBI

19 

Sargent D, Sobrero A, Grothey A, O'Connell MJ, Buyse M, Andre T, Zheng Y, Green E, Labianca R, O'Callaghan C, et al: Evidence for cure by adjuvant therapy in colon cancer: Observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 27:872–877. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Blondy S, David V, Verdier M, Mathonnet M, Perraud A and Christou N: 5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes. Cancer Sci. 111:3142–3154. 2020. View Article : Google Scholar : PubMed/NCBI

21 

Uppada SB, Gowrikumar S, Ahmad R, Kumar B, Szeglin B, Chen X, Smith JJ, Batra SK, Singh AB and Dhawan P: MASTL induces colon cancer progression and chemoresistance by promoting Wnt/β-catenin signaling. Mol Cancer. 17:1112018. View Article : Google Scholar : PubMed/NCBI

22 

Sun Y, Jiang Y, Huang J, Chen H, Liao Y and Yang Z: CISD2 enhances the chemosensitivity of gastric cancer through the enhancement of 5-FU-induced apoptosis and the inhibition of autophagy by AKT/mTOR pathway. Cancer Med. 6:2331–2346. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Liang Y, Hou L, Li L, Li L, Zhu L, Wang Y, Huang X, Hou Y, Zhu D, Zou H, et al: Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway. Oncogene. 39:469–485. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Qu X, Zhai Y, Wei H, Zhang C, Xing G, Yu Y and He F: Characterization and expression of three novel differentiation-related genes belong to the human NDRG gene family. Mol Cell Biochem. 229:35–44. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Vaes N, Lentjes MHFM, Gijbels MJ, Rademakers G, Daenen KL, Boesmans W, Wouters KAD, Geuzens A, Qu X, Steinbusch HPJ, et al: NDRG4, an early detection marker for colorectal cancer, is specifically expressed in enteric neurons. Neurogastroenterol Motil. 29:2017. View Article : Google Scholar : PubMed/NCBI

26 

Kisiel JB, Klepp P, Allawi HT, Taylor WR, Giakoumopoulos M, Sander T, Yab TC, Moum BA, Lidgard GP, Brackmann S, et al: Analysis of DNA methylation at specific loci in stool samples detects colorectal cancer and high-grade dysplasia in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 17:914–921 e5. 2019. View Article : Google Scholar : PubMed/NCBI

27 

Chu D, Zhang Z, Zhou Y, Li Y, Zhu S, Zhang J, Zhao Q, Ji G, Wang W and Zheng J: NDRG4, a novel candidate tumor suppressor, is a predictor of overall survival of colorectal cancer patients. Oncotarget. 6:7584–7596. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Zheng J, Li Y, Zhu S, Li J, Zhao Q, Ji G, Wang W and Chu D: NDRG4 stratifies the prognostic value of body mass index in colorectal cancer. Oncotarget. 7:1311–1322. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Milczarek M, Rossowska J, Klopotowska D, Stachowicz M, Kutner A and Wietrzyk J: Tacalcitol increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating the thymidylate synthase. J Steroid Biochem Mol Biol. 190:139–151. 2019. View Article : Google Scholar : PubMed/NCBI

30 

Lu P, Xu M, Xiong Z, Zhou F and Wang L: Fusobacterium nucleatum prevents apoptosis in colorectal cancer cells via the ANO1 pathway. Cancer Manag Res. 11:9057–9066. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Yang CM, Kang MK, Jung WJ, Joo JS, Kim YJ, Choi Y and Kim HP: p53 expression confers sensitivity to 5-fluorouracil via distinct chromatin accessibility dynamics in human colorectal cancer. Oncol Lett. 21:2262021. View Article : Google Scholar : PubMed/NCBI

32 

Palma S, Raffa CI, Garcia-Fabiani MB, Ferretti VA, Zwenger A, Perez Verdera PV, Llontop A, Rojas Bilbao E, Cuartero V, Abba MC and Lacunza E: RHBDD2 overexpression promotes a chemoresistant and invasive phenotype to rectal cancer tumors via modulating UPR and focal adhesion genes. Biochim Biophys Acta Mol Basis Dis. 1866:1658102020. View Article : Google Scholar : PubMed/NCBI

33 

Yao RQ, Ren C, Xia ZF and Yao YM: Organelle-specific autophagy in inflammatory diseases: A potential therapeutic target underlying the quality control of multiple organelles. Autophagy. 17:385–401. 2021. View Article : Google Scholar : PubMed/NCBI

34 

Zhang X, Zhou T, Li W, Zhang T, Che N and Zu G: Clinicopathological and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer. Pathol Res Pract. 214:1105–1109. 2018. View Article : Google Scholar : PubMed/NCBI

35 

Ji DB and Wu AW: Organoid in colorectal cancer: Progress and challenges. Chin Med J (Engl). 133:1971–1977. 2020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li R, He C, Shen L, Wang S, Shen Y, Feng F, Zhang J and Zheng J: NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321. Oncol Lett 22: 782, 2021.
APA
Li, R., He, C., Shen, L., Wang, S., Shen, Y., Feng, F. ... Zheng, J. (2021). NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321. Oncology Letters, 22, 782. https://doi.org/10.3892/ol.2021.13043
MLA
Li, R., He, C., Shen, L., Wang, S., Shen, Y., Feng, F., Zhang, J., Zheng, J."NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321". Oncology Letters 22.5 (2021): 782.
Chicago
Li, R., He, C., Shen, L., Wang, S., Shen, Y., Feng, F., Zhang, J., Zheng, J."NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321". Oncology Letters 22, no. 5 (2021): 782. https://doi.org/10.3892/ol.2021.13043
Copy and paste a formatted citation
x
Spandidos Publications style
Li R, He C, Shen L, Wang S, Shen Y, Feng F, Zhang J and Zheng J: NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321. Oncol Lett 22: 782, 2021.
APA
Li, R., He, C., Shen, L., Wang, S., Shen, Y., Feng, F. ... Zheng, J. (2021). NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321. Oncology Letters, 22, 782. https://doi.org/10.3892/ol.2021.13043
MLA
Li, R., He, C., Shen, L., Wang, S., Shen, Y., Feng, F., Zhang, J., Zheng, J."NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321". Oncology Letters 22.5 (2021): 782.
Chicago
Li, R., He, C., Shen, L., Wang, S., Shen, Y., Feng, F., Zhang, J., Zheng, J."NDRG4 sensitizes CRC cells to 5‑FU by upregulating DDIT3 expression Corrigendum in /10.3892/ol.2022.13321". Oncology Letters 22, no. 5 (2021): 782. https://doi.org/10.3892/ol.2021.13043
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