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Article

Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer

  • Authors:
    • Kuo-Wang Tsai
    • Ling-Yueh Hu
    • Ting-Wen Chen
    • Sung-Chou Li
    • Meng‑Ru Ho
    • Shou-Yu Yu
    • Ya-Ting Tu
    • Wei-Shone Chen
    • Hing-Chung Lam
  • View Affiliations / Copyright

    Affiliations: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C., Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, R.O.C., Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, R.O.C., Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C., Biodiversity Research Center, Academia Sinica, Taipei, Taiwan, R.O.C., Department of Surgery, Veterans General Hospital, Taipei, Taiwan, R.O.C., Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.
  • Pages: 485-493
    |
    Published online on: November 11, 2014
       https://doi.org/10.3892/or.2014.3598
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Abstract

Endothelin-1 (ET-1) is a small 21-amino acid peptide that is known to exert diverse biological effects on a wide variety of tissues and cell types through its own receptors. The ET-1-ETRA axis is frequently dysfunctional in numerous types of carcinomas, and contributes to the promotion of cell growth and migration. microRNAs (miRNAs) are small non-coding RNAs that play a critical role in carcinogenesis through mRNA degradation or the translational inhibition of cancer-associated protein-coding genes. However, the role of ET-1 and the relationship between ET-1 and miRNAs in gastric cancer remain unknown. Results of the analysis of the database of The Cancer Genome Atlas (TCGA) revealed that ET-1 is significantly overexpressed in gastric cancer cells when compared with its expression in adjacent normal cells. Exogenous ET-1 significantly enhanced gastric cancer cell proliferation, implying that ET-1 plays an oncogenic role in gastric cancer carcinogenesis. Using a luciferase reporter assay we showed that 18 miRNA candidates had a significant silencing effect on ET-1 expression by up to 20% in HEK293T cells. Among them, 5 miRNAs (miR-1, miR-101, miR-125A, miR-144 and let-7c) were shown to be involved in ET-1 silencing through post-transcriptional modulation in gastric cancer. Our data also revealed that DNA hypermethylation contributes to the silenced miR-1 expression in gastric cancer cells. The ectopic expression of miR-1 significantly inhibited AGS cell proliferation by suppressing ET-1 expression. Overall, our study revealed that ET-1 overexpression may be due to DNA hypermethylation resulting in the silencing of miR-1 expression in gastric cancer cells. In addition, we identified several miRNAs as potential modulators for ET-1 in gastric cancer, which may be used as targets for gastric cancer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Tsai K, Hu L, Chen T, Li S, Ho MR, Yu S, Tu Y, Chen W and Lam H: Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer. Oncol Rep 33: 485-493, 2015.
APA
Tsai, K., Hu, L., Chen, T., Li, S., Ho, M., Yu, S. ... Lam, H. (2015). Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer. Oncology Reports, 33, 485-493. https://doi.org/10.3892/or.2014.3598
MLA
Tsai, K., Hu, L., Chen, T., Li, S., Ho, M., Yu, S., Tu, Y., Chen, W., Lam, H."Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer". Oncology Reports 33.1 (2015): 485-493.
Chicago
Tsai, K., Hu, L., Chen, T., Li, S., Ho, M., Yu, S., Tu, Y., Chen, W., Lam, H."Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer". Oncology Reports 33, no. 1 (2015): 485-493. https://doi.org/10.3892/or.2014.3598
Copy and paste a formatted citation
x
Spandidos Publications style
Tsai K, Hu L, Chen T, Li S, Ho MR, Yu S, Tu Y, Chen W and Lam H: Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer. Oncol Rep 33: 485-493, 2015.
APA
Tsai, K., Hu, L., Chen, T., Li, S., Ho, M., Yu, S. ... Lam, H. (2015). Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer. Oncology Reports, 33, 485-493. https://doi.org/10.3892/or.2014.3598
MLA
Tsai, K., Hu, L., Chen, T., Li, S., Ho, M., Yu, S., Tu, Y., Chen, W., Lam, H."Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer". Oncology Reports 33.1 (2015): 485-493.
Chicago
Tsai, K., Hu, L., Chen, T., Li, S., Ho, M., Yu, S., Tu, Y., Chen, W., Lam, H."Emerging role of microRNAs in modulating endothelin-1 expression in gastric cancer". Oncology Reports 33, no. 1 (2015): 485-493. https://doi.org/10.3892/or.2014.3598
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