Up-regulation of microRNA-21 correlates with lower kidney cancer survival.
Up-regulation of microRNA-21 correlates with lower kidney cancer survival.
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DOI：
10.1371/journal.pone.0031060
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dahiya R
中科院分区：
文献类型：
--
作者：
Zaman MS;Shahryari V;Deng G;Thamminana S;Saini S;Majid S;Chang I;Hirata H;Ueno K;Yamamura S;Singh K;Tanaka Y;Tabatabai ZL;Dahiya R
microRNA-21在乳腺癌、结直肠癌、肺癌、头颈部癌等多种肿瘤中表达上调，但其在肾细胞癌（RCC）中的表达调控尚未得到系统研究。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年生存率及病理分期有关。在RCC细胞系中抑制miR-21后进行功能研究。我们研究了体外和体内化疗预防剂染料木素对miR-21表达的影响。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相关。在RCC细胞系中抑制miRNA-21后的功能研究显示细胞周期停滞、诱导凋亡以及降低的侵袭和迁移能力。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的表达减少。Genistein抑制A-498细胞中miR-21的表达，并抑制裸鼠体内注射Genistein处理的A-498细胞形成的肿瘤中miR-21的表达。目前的研究显示miR-21的表达与肾癌的临床特征之间存在明显的相关性。因此，我们认为miR-21可以用作肿瘤标志物，并且其抑制可能被证明在控制具有上调的miR-21的癌症中是有用的。
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.
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