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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
September-2016 Volume 36 Issue 3

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
September-2016 Volume 36 Issue 3

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

Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis

  • Authors:
    • Rui‑Pei Chen
    • Zhen‑Lun Huang
    • Li‑Xuan Liu
    • Meng‑Qi Xiang
    • Guo‑Ping Li
    • Jia‑Lin Feng
    • Bin Liu
    • Ling‑Fei Wu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Information, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Department of Neurosurgery, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
  • Pages: 1649-1657
    |
    Published online on: July 8, 2016
       https://doi.org/10.3892/or.2016.4919
  • 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

Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. Although downregulation of lncRNA maternally expressed gene 3 (MEG3) has been identified in several types of cancers, little is known concerning its biological role and regulatory mechanism in hepatoma. Our previous studies demonstrated that MEG3 induces apoptosis in a p53-dependent manner. The aim of the present study was to determine whether endoplasmic reticulum (ER) stress is involved in MEG3‑induced apoptosis. Recombinant lentiviral vectors containing MEG3 (Lv‑MEG3) were constructed and transfected into HepG2 cells. A 3‑(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, RT‑PCR, flow cytometry, western blot analysis, immunofluorescence and immunohistochemistry were applied. Transfected HepG2 cells were also transplanted into nude mice, and the tumor growth curves were determined. The results showed that the recombinant lentivirus of MEG3 was transfected successfully into the HepG2 cells and the expression level of MEG3 was significantly increased. Ectopic expression of MEG3 inhibited HepG2 cell proliferation in vitro and in vivo, and also induced apoptosis. Ectopic expression of MEG3 increased ER stress‑related proteins 78‑kDa glucose‑regulated protein (GRP78), inositol‑requiring enzyme 1 (IRE1), RNA‑dependent protein kinase‑like ER kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), caspase‑3, as well as p53 and NF‑κB expression accompanied by NF‑κB translocation from the cytoplasm to the nucleus. Furthermore, inhibition of NF‑κB with Bay11‑7082 decreased p53 expression in the MEG3‑transfected cells. These results indicate that MEG3 inhibits cell proliferation and induces apoptosis, partially via the activation of the ER stress and p53 pathway, in which NF‑κB signaling is required for p53 activation in ER stress.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Wang P, Ren Z and Sun P: Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem. 113:1868–1874. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Li Z, Li C, Liu C, Yu S and Zhang Y: Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior. Pituitary. 18:42–47. 2015. View Article : Google Scholar

4 

Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T and Ishino F: Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells. 5:211–220. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Zhou Y, Zhang X and Klibanski A: MEG3 noncoding RNA: A tumor suppressor. J Mol Endocrinol. 48:R45–R53. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Bando T, Kato Y, Ihara Y, Yamagishi F, Tsukada K and Isobe M: Loss of heterozygosity of 14q32 in colorectal carcinoma. Cancer Genet Cytogenet. 111:161–165. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP and Hou YY: Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer. 13:4612013. View Article : Google Scholar : PubMed/NCBI

8 

Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S, Negrini M, Miotto E, Croce CM and Patel T: microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer. Oncogene. 30:4750–4756. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Zhang X, Gejman R, Mahta A, Zhong Y, Rice KA, Zhou Y, Cheunsuchon P, Louis DN and Klibanski A: Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression. Cancer Res. 70:2350–2358. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Liu LX, Deng W, Zhou XT, Chen RP, Xiang MQ, Guo YT, Pu ZJ, Li R, Wang GF and Wu LF: The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells. Int J Oncol. 48:421–429. 2016.

11 

Schröder M: Endoplasmic reticulum stress responses. Cell Mol Life Sci. 65:862–894. 2008. View Article : Google Scholar

12 

Wu LF, Ye YQ, Huang GY, Li HB, Li GP, Pu ZJ, Wei BL and Feng JL: Involvement of endoplasmic reticulum stress in adenosine-induced human hepatoma HepG2 cell apoptosis. Oncol Rep. 26:73–79. 2011.PubMed/NCBI

13 

Giampietri C, Petrungaro S, Conti S, Facchiano A, Filippini A and Ziparo E: Cancer microenvironment and endoplasmic reticulum stress response. Mediators Inflamm. 2015:4172812015. View Article : Google Scholar : PubMed/NCBI

14 

Wu LF, Guo YT, Zhang QH, Xiang MQ, Deng W, Ye YQ, Pu ZJ, Feng JL and Huang GY: Enhanced antitumor effects of adenoviral-mediated siRNA against GRP78 gene on adenosine-induced apoptosis in human hepatoma HepG2 cells. Int J Mol Sci. 15:525–544. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL and Ron D: CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12:982–995. 1998. View Article : Google Scholar : PubMed/NCBI

16 

Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA and Yuan J: Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 403:98–103. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP and Ron D: Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 287:664–666. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C and Klibanski A: Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 282:24731–24742. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Yang PM, Lin YT, Shun CT, Lin SH, Wei TT, Chuang SH, Wu MS and Chen CC: Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53-dependent endoplasmic reticulum stress. Sci Rep. 3:32192013.PubMed/NCBI

20 

Kilkenny C, Browne W, Cuthill IC, Emerson M and Altman DG; NC3Rs Reporting Guidelines Working Group: Animal research: Reporting in vivo experiments: The ARRIVE guidelines. Br J Pharmacol. 160:1577–1579. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Lee AS: The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods. 35:373–381. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Bromati CR, Lellis-Santos C, Yamanaka TS, Nogueira TC, Leonelli M, Caperuto LC, Gorjão R, Leite AR, Anhê GF and Bordin S: UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression. Am J Physiol Regul Integr Comp Physiol. 300:R92–R100. 2011. View Article : Google Scholar

23 

Wu H and Lozano G: NF-kappa B activation of p53. A potential mechanism for suppressing cell growth in response to stress. J Biol Chem. 269:20067–20074. 1994.PubMed/NCBI

24 

Furlong EE, Rein T and Martin F: YY1 and NF1 both activate the human p53 promoter by alternatively binding to a composite element, and YY1 and E1A cooperate to amplify p53 promoter activity. Mol Cell Biol. 16:5933–5945. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Kitamura M: Control of NF-κB and inflammation by the unfolded protein response. Int Rev Immunol. 30:4–15. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Kaneko M, Niinuma Y and Nomura Y: Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2. Biol Pharm Bull. 26:931–935. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Jiang HY, Wek SA, McGrath BC, Scheuner D, Kaufman RJ, Cavener DR and Wek RC: Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses. Mol Cell Biol. 23:5651–5663. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Yamazaki H, Hiramatsu N, Hayakawa K, Tagawa Y, Okamura M, Ogata R, Huang T, Nakajima S, Yao J, Paton AW, et al: Activation of the Akt-NF-kappaB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol. 183:1480–1487. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Zhu J, Liu S, Ye F, Shen Y, Tie Y, Zhu J, Wei L, Jin Y, Fu H, Wu Y, et al: Long noncoding RNA MEG3 interacts with p53 protein and regulates partial p53 target genes in hepatoma cells. PLoS One. 10:e01397902015. View Article : Google Scholar : PubMed/NCBI

30 

Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E and Ben-Neriah Y: NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 431:461–466. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Wu L, Pu Z, Feng J, Li G, Zheng Z and Shen W: The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma. J Surg Oncol. 97:439–444. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Wu LF, Li GP, Su JD, Pu ZJ, Feng JL, Ye YQ and Wei BL: Involvement of NF-kappaB activation in the apoptosis induced by extracellular adenosine in human hepatocellular carcinoma HepG2 cells. Biochem Cell Biol. 88:705–714. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen RP, Huang ZL, Liu LX, Xiang MQ, Li GP, Feng JL, Liu B and Wu LF: Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis. Oncol Rep 36: 1649-1657, 2016.
APA
Chen, R., Huang, Z., Liu, L., Xiang, M., Li, G., Feng, J. ... Wu, L. (2016). Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis. Oncology Reports, 36, 1649-1657. https://doi.org/10.3892/or.2016.4919
MLA
Chen, R., Huang, Z., Liu, L., Xiang, M., Li, G., Feng, J., Liu, B., Wu, L."Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis". Oncology Reports 36.3 (2016): 1649-1657.
Chicago
Chen, R., Huang, Z., Liu, L., Xiang, M., Li, G., Feng, J., Liu, B., Wu, L."Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis". Oncology Reports 36, no. 3 (2016): 1649-1657. https://doi.org/10.3892/or.2016.4919
Copy and paste a formatted citation
x
Spandidos Publications style
Chen RP, Huang ZL, Liu LX, Xiang MQ, Li GP, Feng JL, Liu B and Wu LF: Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis. Oncol Rep 36: 1649-1657, 2016.
APA
Chen, R., Huang, Z., Liu, L., Xiang, M., Li, G., Feng, J. ... Wu, L. (2016). Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis. Oncology Reports, 36, 1649-1657. https://doi.org/10.3892/or.2016.4919
MLA
Chen, R., Huang, Z., Liu, L., Xiang, M., Li, G., Feng, J., Liu, B., Wu, L."Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis". Oncology Reports 36.3 (2016): 1649-1657.
Chicago
Chen, R., Huang, Z., Liu, L., Xiang, M., Li, G., Feng, J., Liu, B., Wu, L."Involvement of endoplasmic reticulum stress and p53 in lncRNA MEG3-induced human hepatoma HepG2 cell apoptosis". Oncology Reports 36, no. 3 (2016): 1649-1657. https://doi.org/10.3892/or.2016.4919
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