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PMID: 24515776 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

MiR-148a regulates MEG3 in gastric cancer by targeting DNA methyltransferase 1.

Medical oncology (Northwood, London, England) ·Vol. 31 ·No. 3 ·2014-03-00 ·Pages 879

Yan J, Guo X, Xia J, Shan T, Gu C, Liang Z, Zhao W, Jin S

Abstract

The long non-coding RNA MEG3 has been reported to be a tumor suppressor in a number of malignant tumors including gastric cancer. Several studies have shown that the regulation of MEG3 may attribute to the promoter hypermethylation. However, the mechanism of MEG3 regulation in gastric cancer is still not well understood. MiR-148a can suppress gastric tumorigenesis through regulating the expression of target genes such as DNA methyltransferase 1(DNMT-1). We examined the expression of MEG3 in 52 gastric cancer samples using quantitative real-time PCR and found the down-regulation of MEG3 in both gastric cancer tissues and cell lines. The positive correlation of MEG3 and miR-148a was further confirmed in SGC-7901 and BGC-823 gastric cancer cell lines. Hypermethylation of MEG3 differentially methylated regions was identified by methylation-specific PCR, and MEG3 expression was increased with the inhibition of methylation with siRNA to DNMT-1 in gastric cancer cells. In addition, transfection of MEG3 siRNA into gastric cancer cells diminished the suppression of proliferation induced by overexpression of miR-148a. Our results suggest that the suppression of miR-148a may contribute to the down-regulation of MEG3 in gastric cancer by modulation of DNMT-1.

MeSH Terms
Blotting, Western Cell Proliferation DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases/genetics,metabolism DNA Methylation Gastric Mucosa/metabolism Gene Expression Regulation, Neoplastic Humans MicroRNAs/genetics Prognosis Promoter Regions, Genetic/genetics RNA, Long Noncoding/genetics RNA, Messenger/genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms/genetics,metabolism,pathology
Chemicals
MEG3 non-coding RNA, human MIRN148 microRNA, human MicroRNAs RNA, Long Noncoding RNA, Messenger DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Yan Jiang
Department of General Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, 214002, China.
Guo Xiaoqiang
Xia Jiazeng
Shan Tin
Gu Chen
Liang Zheng
Zhao Wei
Jin Shimao
References (29)
29 references, click to expand
  1. Integrative network analysis reveals active microRNAs and their functions in gastric cancer.
    BMC Syst Biol. 2011 Jun 26;5:99 PMID: 21703006
  2. Integrated microRNA network analyses identify a poor-prognosis subtype of gastric cancer characterized by the miR-200 family.
    Clin Cancer Res. 2014 Feb 15;20(4):878-89 PMID: 24352645
  3. The imprinted H19 lncRNA antagonizes let-7 microRNAs.
    Mol Cell. 2013 Oct 10;52(1):101-12 PMID: 24055342
  4. Loss of imprinting and allelic switching at the DLK1-MEG3 locus in human hepatocellular carcinoma.
    PLoS One. 2012;7(11):e49462 PMID: 23145177
  5. MicroRNAs: target recognition and regulatory functions.
    Cell. 2009 Jan 23;136(2):215-33 PMID: 19167326
  6. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression.
    BMC Cancer. 2013 Oct 07;13:461 PMID: 24098911
  7. Methylation analysis of the imprinted DLK1-GTL2 domain supports the random parental origin of the IGH-involving del(14q) in B-cell malignancies.
    Epigenetics. 2009 Oct 1;4(7):469-75 PMID: 19786834
  8. Alteration of transcriptional profile in human bronchial epithelial cells induced by cigarette smoke condensate.
    Toxicol Lett. 2009 Oct 8;190(1):23-31 PMID: 19559774
  9. Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma.
    Hum Mol Genet. 2006 Mar 15;15(6):821-30 PMID: 16439445
  10. Altered expression of imprinted genes in Wilms tumors.
    Oncol Rep. 2011 Mar;25(3):817-23 PMID: 21174059
  11. Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation.
    Genome Res. 2000 Nov;10(11):1711-8 PMID: 11076856
  12. Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR.
    PLoS One. 2013 Aug 01;8(8):e70372 PMID: 23936419
  13. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer.
    Med Oncol. 2012 Dec;29(4):2701-9 PMID: 22167392
  14. MicroRNA-148a can regulate runt-related transcription factor 3 gene expression via modulation of DNA methyltransferase 1 in gastric cancer.
    Mol Cells. 2013 Apr;35(4):313-9 PMID: 23549984
  15. Global cancer statistics.
    CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90 PMID: 21296855
  16. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer.
    Mol Biosyst. 2013 Mar;9(3):407-11 PMID: 23295831
  17. Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression.
    Cancer Res. 2010 Mar 15;70(6):2350-8 PMID: 20179190
  18. MicroRNAs in stress signaling and human disease.
    Cell. 2012 Mar 16;148(6):1172-87 PMID: 22424228
  19. microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer.
    Oncogene. 2011 Nov 24;30(47):4750-6 PMID: 21625215
  20. The functions of animal microRNAs.
    Nature. 2004 Sep 16;431(7006):350-5 PMID: 15372042
  21. Identification of imprinting regulators at the Meg3 differentially methylated region.
    Genomics. 2012 Sep;100(3):184-94 PMID: 22709555
  22. Gene expression and IG-DMR hypomethylation of maternally expressed gene 3 in developing corticospinal neurons.
    Gene Expr Patterns. 2013 Jan-Feb;13(1-2):51-6 PMID: 23195472
  23. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
  24. microRNA-449a functions as a tumor-suppressor in gastric adenocarcinoma by targeting Bcl-2.
    Oncol Lett. 2013 Dec;6(6):1713-1718 PMID: 24260067
  25. A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells.
    J Clin Endocrinol Metab. 2003 Nov;88(11):5119-26 PMID: 14602737
  26. Long noncoding RNAs: cellular address codes in development and disease.
    Cell. 2013 Mar 14;152(6):1298-307 PMID: 23498938
  27. Long non-coding RNAs and cancer: a new frontier of translational research?
    Oncogene. 2012 Oct 25;31(43):4577-87 PMID: 22266873
  28. microRNA-32 inhibits the proliferation and invasion of the SGC-7901 gastric cancer cell line in vitro.
    Oncol Lett. 2014 Jan;7(1):270-274 PMID: 24348862
  29. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer.
    Tumour Biol. 2014 Feb;35(2):1065-73 PMID: 24006224
Article Info
Journal
Medical oncology (Northwood, London, England)
Abbr.
Med Oncol
ISSN
1559-131X
Published
2014-03-00
Epub
2014-00-11
Pages
879
Language
English
Region
United States
NLM ID
9435512
Subset
IM
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