Up-regulation of microRNA-21 correlates with lower kidney cancer survival

Mohd Saif Zaman, Varahram Shahryari, Guoren Deng, Sobha Thamminana, Sharonjot Saini, Shahana Majid, Inik Chang, Hiroshi Hirata, Koji Ueno, Soichiro Yamamura, Kamaldeep Singh, Yuichiro Tanaka, Z. Laura Tabatabai, Rajvir Dahiya

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109 Scopus citations

Abstract

Background: MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically. Methods and Results: We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR. The expression level of miR-21 was correlated with 5 year survival and the pathological stage. Functional studies were done after inhibiting miR-21 in RCC cell lines. We studied in vitro and in vivo effects of the chemo preventive agent genistein on miR-21 expression. In 48 cases (90%), miR-21 was increased. All patients with low miR-21 expression survived 5 years, while with high miR-21 expression, only 50% survived. Higher expression of miR-21 is associated with an increase in the stage of renal cancer. Functional studies after inhibiting miRNA-21 in RCC cell lines show cell cycle arrest, induction of apoptosis and reduced invasive and migratory capabilities. Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. Genistein inhibited the expression of miR-21 in A-498 cells and in the tumors formed after injecting genistein treated A-498 cells in nude mice besides inhibiting tumor formation. Conclusions: The current study shows a clear correlation between miR-21 expression and clinical characteristics of renal cancer. Thus we believe that miR-21 can be used as a tumor marker and its inhibition may prove to be useful in controlling cancers with up-regulated miR-21.

Original languageEnglish (US)
Article numbere31060
JournalPloS one
Volume7
Issue number2
DOIs
StatePublished - Feb 8 2012

ASJC Scopus subject areas

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

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    Zaman, M. S., Shahryari, V., Deng, G., Thamminana, S., Saini, S., Majid, S., Chang, I., Hirata, H., Ueno, K., Yamamura, S., Singh, K., Tanaka, Y., Tabatabai, Z. L., & Dahiya, R. (2012). Up-regulation of microRNA-21 correlates with lower kidney cancer survival. PloS one, 7(2), [e31060]. https://doi.org/10.1371/journal.pone.0031060