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

  • Published online on: November 11, 2014     https://doi.org/10.3892/or.2014.3598
  • Pages: 485-493
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

January-2015
Volume 33 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

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