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

Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 11/2012; 7(11):e50203. DOI: 10.1371/journal.pone.0050203
Source: PubMed


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.
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.
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.

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Available from: Shinichiro Fukuhara, Oct 01, 2015
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    • "Zaman et al. (75) demonstrated that also miR-23-3p is an oncogenic miRNA targeting PTEN and its expression level was increased in RCC. Wang et al. showed a correlation of miR-100 up-regulation with poor prognosis in RCC patients (76). "
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    • "The protein expression levels were quantified by optical densitometry using ImageJ Software version 1.46 ( Fold change was calculated as the ratio between the net intensity of each sample divided by control GAPDH and the Ad/pri-miR-21, Ad/miR-21/inhibitor and Ad/con infected samples divided by the GAPDH [32]. "
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    • "Ectopic expression of miR-23b resulted in significant inhibition of cell proliferation, colony formation, migration/invasion and induction of cell cycle arrest and apoptosis in bladder cancer cells. Expression of miR-23b in cancer is somewhat controversial because it has been found to be either up-regulated and oncogenic in kidney cancer where it caused translational repression of tumor suppressor PTEN gene [13] or down-regulated and a tumor suppressor in prostate cancer where it directly targets Src kinase and Akt oncogenes [14], while our study indicates it is a tumor suppressor in bladder cancer. Previous studies have shown that microRNAs are highly tissue specific and they can act as tumor suppressor or oncogenes [15], [16]. "
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