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

Authors
 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 
Citation
 PLoS One, Vol.7(11) : e50203, 2012 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2012
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91743
DOI
10.1371/journal.pone.0050203
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실)
Yonsei Authors
장인익(Chang, In Ik)
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