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
April-2018 Volume 15 Issue 4

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
April-2018 Volume 15 Issue 4

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
Article Open Access

miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1

  • Authors:
    • Huaijie Shi
    • Xiaojing Chen
    • Hao Jiang
    • Xujie Wang
    • Hao Yu
    • Pijiang Sun
    • Xin Sui
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Weihai Central Hospital, Weihai, Shandong 264400, P.R. China, First Department of Radiotherapy, Qingdao Center Hospital, Qingdao, Shandong 266000, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4944-4950
    |
    Published online on: January 31, 2018
       https://doi.org/10.3892/ol.2018.7907
  • 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

Gastric cancer (GC) is the fourth most common malignant tumor globally. The highest incidence of GC is found in Eastern Asia, particularly in China. It is therefore imperative to further elucidate the molecular pathogenesis of GC in order to identify new biomarkers and targets for effective therapy. In the present study, we determined whether miR-148a was aberrantly downregulated in gastric cancer tissues and significantly correlated with aggressive clinicopathological character­istics in the MGC-803, HGC-27 and GES-1 cell lines using reverse transcription-quantitative PCR and western blot analysis. The cell lines were obtained from 60 patients who presented at our hospital between September 2010 and July 2015. The results showed that, miR-148a was aberrantly downregulated in GC tissues and its expression was relatively lower in the MGC-803 and HGC-27 GC cell lines than in the normal gastric epithelial cell line, GES-1. The clinicopathological analysis revealed that a decrease of miR‑148a was significantly correlated with lymph-node metastasis (P<0.01) and tumor node metastasis (TNM) stage (P<0.05). The transwell assay showed that the re-expression of miR‑148a significantly reduced cell migratory and invasive abilities in vitro (P<0.01). The luciferase assay confirmed that, DNA methyl­transferase 1 (DNMT1) was a direct and functional target of miR-148a. The miR-148a inhibitor increased the expression of DNMT1 in HGC-27 cells and the re-expression of miR-148a reduced the expression of DNMT1 in MGC-803 cells as confirmed by western blot analysis. Furthermore, we found that the re-expression of DNMT1 reversed the inhibition of cell migration and invasion induced by miR-148a. Taken together, we demonstrated that miR-148a suppresses cell invasion and migration in gastric cancer by regulating DNMT1 expression. The miR-148a/DNMT1 axis may therefore be a new potential target for GC therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, Negri E, La Vecchia C and Lunet N: Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 50:1330–1344. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, Malvezzi M and La Vecchia C: Recent patterns in gastric cancer: A global overview. Int J Cancer. 125:666–673. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Polk DB and Peek RM Jr: Helicobacter pylori: Gastric cancer and beyond. Nat Rev Cancer. 10:403–414. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Fox JG, Rogers AB, Whary MT, Ge Z, Ohtani M, Jones EK and Wang TC: Accelerated progression of gastritis to dysplasia in the pyloric antrum of TFF2 −/− C57BL6 × Sv129 Helicobacter pylori-infected mice. Am J Pathol. 171:1520–1528. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Ding SZ, Goldberg JB and Hatakeyama M: Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis. Future Oncol. 6:851–862. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Zhao XD, Lu YY, Guo H, Xie HH, He LJ, Shen GF, Zhou JF, Li T, Hu SJ, Zhou L, et al: MicroRNA-7/NF-κB signaling regulatory feedback circuit regulates gastric carcinogenesis. J Cell Biol. 210:613–627. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Cui R, Meng W, Sun HL, Kim T, Ye Z, Fassan M, Jeon YJ, Li B, Vicentini C, Peng Y, et al: MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer. Proc Natl Acad Sci USA. 112:pp. E4288–E4297. 2015; View Article : Google Scholar : PubMed/NCBI

10 

Ohta K, Hoshino H, Wang J, Ono S, Iida Y, Hata K, Huang SK, Colquhoun S and Hoon DS: MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A. Oncotarget. 6:3211–3224. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Liu R, Gu J, Jiang P, Zheng Y, Liu X, Jiang X, Huang E, Xiong S, Xu F, Liu G, et al: DNMT1-microRNA126 epigenetic circuit contributes to esophageal squamous cell carcinoma growth via ADAM9-EGFR-AKT signaling. Clin Cancer Res. 21:854–863. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Wang Y, Liu C, Luo M, Zhang Z, Gong J, Li J, You L, Dong L, Su R, Lin H, et al: Chemotherapy-Induced miRNA-29c/Catenin-δ Signaling Suppresses Metastasis in Gastric Cancer. Cancer Res. 75:1332–1344. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Han TS, Hur K, Xu G, Choi B, Okugawa Y, Toiyama Y, Oshima H, Oshima M, Lee HJ, Kim VN, et al: MicroRNA-29c mediates initiation of gastric carcinogenesis by directly targeting ITGB1. Gut. 64:203–214. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, Liu L, Jia D, Tian Q, Wu J, et al: MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 17:7574–7583. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M and Jones PA: Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G(0)/G(1) to S phase transition in normal and tumor cells. Nucleic Acids Res. 28:2108–2113. 2000. View Article : Google Scholar : PubMed/NCBI

17 

He M, Fan J, Jiang R, Tang WX and Wang ZW: Expression of DNMTs and genomic DNA methylation in gastric signet ring cell carcinoma. Mol Med Rep. 8:942–948. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Hermann A, Gowher H and Jeltsch A: Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci. 61:2571–2587. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Jiang C and Fang G: MiR-148a promotes myocardial differentiation of human bone mesenchymal stromal cells via DNA methyltransferase 1 (DNMT1). Cell Biol Int. Jun 28–2017.(Epub ahead of print). View Article : Google Scholar

20 

Joshi P, Jeon YJ, Laganà A, Middleton J, Secchiero P, Garofalo M and Croce CM: MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC. Proc Natl Acad Sci USA. 112:pp. 8650–8655. 2015; View Article : Google Scholar : PubMed/NCBI

21 

Hanoun N, Delpu Y, Suriawinata AA, Bournet B, Bureau C, Selves J, Tsongalis GJ, Dufresne M, Buscail L, Cordelier P, et al: The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin Chem. 56:1107–1118. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Sakamoto N, Naito Y, Oue N, Sentani K, Uraoka N, Zarni Oo H, Yanagihara K, Aoyagi K, Sasaki H and Yasui W: MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis. Cancer Sci. 105:236–243. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Yu B, Lv X, Su L, Li J, Yu Y, Gu Q, Yan M, Zhu Z and Liu B: MiR-148a functions as a tumor suppressor by targeting CCK-BR via inactivating STAT3 and Akt in human gastric cancer. PLoS One. 11:e01589612016. View Article : Google Scholar : PubMed/NCBI

24 

Fiedler J, Batkai S and Thum T: MicroRNA-based therapy in cardiology. Herz. 39:194–200. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Song Y, Xu Y, Wang Z, Chen Y, Yue Z, Gao P, Xing C and Xu H: MicroRNA-148b suppresses cell growth by targeting cholecystokinin-2 receptor in colorectal cancer. Int J Cancer. 131:1042–1051. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Hino R, Uozaki H, Murakami N, Ushiku T, Shinozaki A, Ishikawa S, Morikawa T, Nakaya T, Sakatani T, Takada K, et al: Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 69:2766–2774. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Zhang BG, Hu L, Zang MD, Wang HX, Zhao W, Li JF, Su LP, Shao Z, Zhao X, Zhu ZG, et al: Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFκB pathway in gastric cancer development. Oncotarget. 7:9788–9800. 2016.PubMed/NCBI

28 

Mutze K, Langer R, Schumacher F, Becker K, Ott K, Novotny A, Hapfelmeier A, Höfler H and Keller G: DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer. Eur J Cancer. 47:1817–1825. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Qiu H, Yashiro M, Shinto O, Matsuzaki T and Hirakawa K: DNA methyltransferase inhibitor 5-aza-CdR enhances the radiosensitivity of gastric cancer cells. Cancer Sci. 100:181–188. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shi H, Chen X, Jiang H, Wang X, Yu H, Sun P and Sui X: miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1. Oncol Lett 15: 4944-4950, 2018.
APA
Shi, H., Chen, X., Jiang, H., Wang, X., Yu, H., Sun, P., & Sui, X. (2018). miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1. Oncology Letters, 15, 4944-4950. https://doi.org/10.3892/ol.2018.7907
MLA
Shi, H., Chen, X., Jiang, H., Wang, X., Yu, H., Sun, P., Sui, X."miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1". Oncology Letters 15.4 (2018): 4944-4950.
Chicago
Shi, H., Chen, X., Jiang, H., Wang, X., Yu, H., Sun, P., Sui, X."miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1". Oncology Letters 15, no. 4 (2018): 4944-4950. https://doi.org/10.3892/ol.2018.7907
Copy and paste a formatted citation
x
Spandidos Publications style
Shi H, Chen X, Jiang H, Wang X, Yu H, Sun P and Sui X: miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1. Oncol Lett 15: 4944-4950, 2018.
APA
Shi, H., Chen, X., Jiang, H., Wang, X., Yu, H., Sun, P., & Sui, X. (2018). miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1. Oncology Letters, 15, 4944-4950. https://doi.org/10.3892/ol.2018.7907
MLA
Shi, H., Chen, X., Jiang, H., Wang, X., Yu, H., Sun, P., Sui, X."miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1". Oncology Letters 15.4 (2018): 4944-4950.
Chicago
Shi, H., Chen, X., Jiang, H., Wang, X., Yu, H., Sun, P., Sui, X."miR-148a suppresses cell invasion and migration in gastric cancer by targeting DNA methyltransferase 1". Oncology Letters 15, no. 4 (2018): 4944-4950. https://doi.org/10.3892/ol.2018.7907
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