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Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.

Publication ,  Journal Article
Oh, H-K; Tan, AL-K; Das, K; Ooi, C-H; Deng, N-T; Tan, IB; Beillard, E; Lee, J; Ramnarayanan, K; Rha, S-Y; Palanisamy, N; Voorhoeve, PM; Tan, P
Published in: Clin Cancer Res
May 1, 2011

PURPOSE: MicroRNAs (miRNA) play pivotal oncogenic and tumor-suppressor roles in several human cancers. We sought to discover novel tumor-suppressor miRNAs in gastric cancer (GC). EXPERIMENTAL DESIGN: Using Agilent miRNA microarrays, we compared miRNA expression profiles of 40 primary gastric tumors and 40 gastric normal tissues, identifying miRNAs significantly downregulated in gastric tumors. RESULTS: Among the top 80 miRNAs differentially expressed between gastric tumors and normals (false discovery rate < 0.01), we identified hsa-miR-486 (miR-486) as a significantly downregulated miRNA in primary GCs and GC cell lines. Restoration of miR-486 expression in GC cell lines (YCC3, SCH and AGS) caused suppression of several pro-oncogenic traits, whereas conversely inhibiting miR-486 expression in YCC6 GC cells enhanced cellular proliferation. Array-CGH analysis of 106 primary GCs revealed genomic loss of the miR-486 locus in approximately 25% to 30% of GCs, including two tumors with focal genomic losses specifically deleting miR-486, consistent with miR-486 playing a tumor-suppressive role. Bioinformatic analysis identified the secreted antiapoptotic glycoprotein OLFM4 as a potential miR-486 target. Restoring miR-486 expression in GC cells decreased endogenous OLFM4 transcript and protein levels, and also inhibited expression of luciferase reporters containing an OLFM4 3' untranslated region with predicted miR-486 binding sites. Supporting the biological relevance of OLFM4 as a miR-486 target, proliferation in GC cells was also significantly reduced by OLFM4 silencing. CONCLUSIONS: miR-486 may function as a novel tumor-suppressor miRNA in GC. Its antioncogenic activity may involve the direct targeting and inhibition of OLFM4.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 1, 2011

Volume

17

Issue

9

Start / End Page

2657 / 2667

Location

United States

Related Subject Headings

  • Stomach Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms
  • Microarray Analysis
  • MicroRNAs
  • Humans
  • Granulocyte Colony-Stimulating Factor
  • Genomic Instability
  • Genes, Tumor Suppressor
  • Gene Expression Regulation, Neoplastic
 

Citation

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Oh, H.-K., Tan, A.-K., Das, K., Ooi, C.-H., Deng, N.-T., Tan, I. B., … Tan, P. (2011). Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer. Clin Cancer Res, 17(9), 2657–2667. https://doi.org/10.1158/1078-0432.CCR-10-3152
Oh, Hue-Kian, Angie Lay-Keng Tan, Kakoli Das, Chia-Huey Ooi, Nian-Tao Deng, Iain Beehuat Tan, Emmanuel Beillard, et al. “Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.Clin Cancer Res 17, no. 9 (May 1, 2011): 2657–67. https://doi.org/10.1158/1078-0432.CCR-10-3152.
Oh H-K, Tan AL-K, Das K, Ooi C-H, Deng N-T, Tan IB, et al. Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer. Clin Cancer Res. 2011 May 1;17(9):2657–67.
Oh, Hue-Kian, et al. “Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer.Clin Cancer Res, vol. 17, no. 9, May 2011, pp. 2657–67. Pubmed, doi:10.1158/1078-0432.CCR-10-3152.
Oh H-K, Tan AL-K, Das K, Ooi C-H, Deng N-T, Tan IB, Beillard E, Lee J, Ramnarayanan K, Rha S-Y, Palanisamy N, Voorhoeve PM, Tan P. Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer. Clin Cancer Res. 2011 May 1;17(9):2657–2667.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

May 1, 2011

Volume

17

Issue

9

Start / End Page

2657 / 2667

Location

United States

Related Subject Headings

  • Stomach Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasms
  • Microarray Analysis
  • MicroRNAs
  • Humans
  • Granulocyte Colony-Stimulating Factor
  • Genomic Instability
  • Genes, Tumor Suppressor
  • Gene Expression Regulation, Neoplastic