Plos One, 2012, 7(11): e50203.

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

Mohd S Zaman, Sobha Thamminana, Varahram Shahryari, et al

Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America; Wayne State University School of Medicine, United States of America

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.

美国《公共科学图书馆一》，2012年11月

在肾癌中通过致癌 miR-23b-3p抑制 PTEN 基因的表达

穆赫德 S 萨曼，索帕 撒米娜，薇艾哈姆 沙瑞亚日，等

美国旧金山退伍军人事务医学中心泌尿外科和加利福尼亚大学; 美国韦恩州立医科大学

背景：

miR- 23b 位于第9号染色体，并且在不同的器官，特别是与癌症发展有关的组织中扮演不同角色。然而， miR-23b-3p 在肾细胞癌 (RCC) 中的功能性作用没有被报道。

方法和结果：

我们使用实时荧光定量 PCR技术检测了 miR-23b-3p在29 对肾细胞癌及其正常匹配组织的水平。miR-23b-3p的表达水平与肾癌患者的 5 年生存率呈正相关的关系。在 15个 例子中 （52%），miR-23b-3 p 的表达被发现变高。miR-23b-3p的表达水平从中等到低的患者全部存活 5 年，而那些 miR-23b-3p 的表达高的患者，只有 50%存活。在RCC细胞中中止 miR-23b-3p的表达后，表现出诱导细胞凋亡及侵袭能力减弱。通过 3′UTR 记录实验我们发现miR-23b-3p直接靶向 PTEN 基因。miR-23b-3p的抑制诱导 PTEN 基因与 PI3 激酶、 总 Akt 和 IL-32的表达相应减少。免疫组织化学显示在组织样本癌变区域PTEN 蛋白表达的缺乏同时这里miR-23b-3p的表达较高。我们研究了膳食性化学预防药物金雀异黄素对miR-23b-3p 表达的体外影响，发现其抑制了miR-23b-3p在RCC细胞中的表达。

结论：

目前的研究表明miR-23b-3p 是一种致癌的 miRNA，在RCC中抑制了 PTEN 抑癌基因。因此，miR-23b-3p的抑制可能成为治疗肾细胞癌的靶点。