Plos One, 2012, 7(2):e31060-e31060.

Up-Regulation of MicroRNA-21 Correlates with Lower Kidney Cancer Survival

Mohd Saif Zaman, Varahram Shahryari, Guoren Deng,et al

Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America; The University of Texas M.D Anderson Cancer Center, United States of America

Background

MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically.

Methods and Results

We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR. The expression level of miR-21 was correlated with 5 year survival and the pathological stage. Functional studies were done after inhibiting miR-21 in RCC cell lines. We studied in vitro and in vivo effects of the chemo preventive agent genistein on miR-21 expression. In 48 cases (90%), miR-21 was increased. All patients with low miR-21 expression survived 5 years, while with high miR-21 expression, only 50% survived. Higher expression of miR-21 is associated with an increase in the stage of renal cancer. Functional studies after inhibiting miRNA-21 in RCC cell lines show cell cycle arrest, induction of apoptosis and reduced invasive and migratory capabilities. Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. Genistein inhibited the expression of miR-21 in A-498 cells and in the tumors formed after injecting genistein treated A-498 cells in nude mice besides inhibiting tumor formation.

Conclusions

The current study shows a clear correlation between miR-21 expression and clinical characteristics of renal cancer. Thus we believe that miR-21 can be used as a tumor marker and its inhibition may prove to be useful in controlling cancers with up-regulated miR-21.

美国《公共科学图书馆一》，2012年2月

与较低的肾癌存活率相关的上调MicroRNA-21

穆赫德 赛义夫 萨曼，薇艾哈姆 沙瑞亚日，邓国仁，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；美国德克萨斯大学麦迪安德森癌症中心

背景：

在各种各样的癌症如乳腺癌、 结直肠癌、 肺癌、 头和颈部癌中miRNA-21的表达上调。然而，miR-21 在肾细胞癌 (RCC) 的调节有尚未被系统研究。

方法和结果：

我们使用实时荧光定量 PCR技术检测了 miR-21在54 对肾细胞癌及其正常匹配组织的水平。miR-21 的表达水平与 5 年生存率和病理分期呈正相关的关系。在RCC细胞中抑制 miR-21后进行功能性研究。我们研究了化学预防药物金雀异黄素对miR-21 在体外和体内表达的影响。在48 例 中（90%)，miR -21被提高。 miR-21 表达水平低的所有患者都存活 了5 年，而miR-21 表达高的患者，只有 50%幸存下来。miR- 21 更高的表达与肾癌阶段的进展相关联。在RCC细胞中抑制 miRNA- 21后的功能研究发现细胞周期阻滞，诱导细胞凋亡及侵袭和迁移能力减弱。免疫印迹分析表明 p21 和 p38 MAP激酶基因表达的提高及细胞周期蛋白 E2 的减少。金雀异黄素抑制了miR-21的表达在 A-498 细胞和注射金雀异黄素治疗后 的裸鼠体内A-498 细胞中肿瘤的形成。

结论：

目前的研究表明在miR-21 表达与肾癌临床特点之间存在明显的联系。因此我们相信 miR-21 可以作为肿瘤标志物，并且其抑制作用证明上调 miR-21有益于控制癌症。