Inhibition of PTEN Gene Expression by Oncogenic miR-23b-3p in Renal Cancer

Mohd Saif Zaman, Sobha Thamminana, Varahram Shahryari, Takeshi Chiyomaru, Guoren Deng, Sharanjot Saini, Shahana Majid, Shinichiro Fukuhara, Inik Chang, Sumit Arora, Hiroshi Hirata, Koji Ueno, Kamaldeep Singh, Yuichiro Tanaka, Rajvir Dahiya

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82 Scopus citations

Abstract

Background: miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC) has not been reported. Methods and Results: We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR. The expression level of miR-23b-3p was correlated with the 5 year survival rate of renal cancer patients. In 15 cases (52%), miR-23b-3p expression was found to be high. All patients with moderate to low miR-23b-3p expression survived 5 years, while those with high miR-23b-3p expression, only 50% survived. After knocking down miRNA-23b-3p expression in RCC cell lines, there was an induction of apoptosis and reduced invasive capabilities. MiR-23b-3p was shown to directly target PTEN gene through 3′UTR reporter assays. Inhibition of miR-23b-3p induces PTEN gene expression with a concomitant reduction in PI3-kinase, total Akt and IL-32. Immunohistochemistry showed the lack of PTEN protein expression in cancerous regions of tissue samples where the expression of miR-23b-3p was high. We studied the in vitro effects of the dietary chemo preventive agent genistein on miR-23b-3p expression and found that it inhibited expression of miR-23b-3p in RCC cell lines. Conclusions: The current study shows that miR-23b-3p is an oncogenic miRNA and inhibits PTEN tumor suppressor gene in RCC. Therefore, inhibition of miR-23b-3p may be a useful therapeutic target for the treatment of renal cell carcinoma.

Original languageEnglish (US)
Article numbere50203
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 26 2012

ASJC Scopus subject areas

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

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    Zaman, M. S., Thamminana, S., Shahryari, V., Chiyomaru, T., Deng, G., Saini, S., Majid, S., Fukuhara, S., Chang, I., Arora, S., Hirata, H., Ueno, K., Singh, K., Tanaka, Y., & Dahiya, R. (2012). Inhibition of PTEN Gene Expression by Oncogenic miR-23b-3p in Renal Cancer. PloS one, 7(11), [e50203]. https://doi.org/10.1371/journal.pone.0050203