MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer

Ji Young Shin, Young Il Kim, Soo Jeong Cho, Mi Kyung Lee, Myeong Cherl Kook, Jun Ho Lee, Sang Soo Lee, Hassan Ashktorab, Duane T. Smoot, Keun Won Ryu, Young Woo Kim, Il Ju Choi

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Abstract

MicroRNAs (miRNAs) play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC) including lymph node (LN) metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage≥IB, 35.0% vs. 12.8%, p = 0.045) and higher rate of LN metastasis (30.0% vs. 5.1%, p = 0.014) than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p = 0.042). Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA-135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.

Original languageEnglish (US)
Article numbere85205
JournalPloS one
Volume9
Issue number1
DOIs
StatePublished - Jan 21 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Shin, J. Y., Kim, Y. I., Cho, S. J., Lee, M. K., Kook, M. C., Lee, J. H., Lee, S. S., Ashktorab, H., Smoot, D. T., Ryu, K. W., Kim, Y. W., & Choi, I. J. (2014). MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. PloS one, 9(1), [e85205]. https://doi.org/10.1371/journal.pone.0085205