Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2012;7(2):e31060. doi: 10.1371/journal.pone.0031060. Epub 2012 Feb 8.
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.
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.
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.
miR-21 在多种癌症中上调，如乳腺癌、结直肠癌、肺癌、头颈部等。然而，miR-21 在肾细胞癌（RCC）中的调节尚未得到系统研究。
我们通过实时 PCR 测量了 54 对肾癌及其正常匹配组织中的 miR-21 水平。miR-21 的表达水平与 5 年生存率和病理分期相关。在 RCC 细胞系中抑制 miR-21 后进行功能研究。我们研究了化学预防剂金雀异黄素对 miR-21 表达的体外和体内影响。在 48 例（90%）中，miR-21 增加。所有低 miR-21 表达的患者均存活 5 年，而高 miR-21 表达的患者仅 50%存活。miR-21 的高表达与肾癌分期的增加有关。在 RCC 细胞系中抑制 miRNA-21 后的功能研究表明细胞周期停滞、诱导细胞凋亡以及降低侵袭和迁移能力。Western blot 分析显示 p21 和 p38 MAP 激酶基因的表达增加，细胞周期蛋白 E2 减少。金雀异黄素抑制 A-498 细胞中 miR-21 的表达，并抑制在裸鼠中注射金雀异黄素处理的 A-498 细胞形成的肿瘤形成。
本研究表明 miR-21 的表达与肾癌的临床特征之间存在明确的相关性。因此，我们认为 miR-21 可以用作肿瘤标志物，其抑制可能对控制上调 miR-21 的癌症有用。
