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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 
Issue Date
2012
MeSH
Apoptosis/genetics ; Base Sequence ; Carcinoma, Renal Cell/genetics* ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/mortality ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic* ; Genistein/metabolism ; Humans ; Kidney Neoplasms/genetics* ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/mortality ; MicroRNAs/genetics* ; MicroRNAs/metabolism ; PTEN Phosphohydrolase/genetics* ; PTEN Phosphohydrolase/metabolism ; RNA Interference
Keywords
Apoptosis/genetics ; Base Sequence ; Carcinoma, Renal Cell/genetics* ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/mortality ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Gene Expression Regulation, Neoplastic* ; Genistein/metabolism ; Humans ; Kidney Neoplasms/genetics* ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/mortality ; MicroRNAs/genetics* ; MicroRNAs/metabolism ; PTEN Phosphohydrolase/genetics* ; PTEN Phosphohydrolase/metabolism ; RNA Interference
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.
Files in This Item:
T201206070.pdf Download
DOI
23189187
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Chang, In Ik(장인익)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91743
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