miRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition Signaling
miRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition Signaling
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DOI：
10.1158/1535-7163.mct-12-0100
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发表时间：
2012-05-01
影响因子：
5.7
通讯作者：
Ray, Ratna B.
中科院分区：
文献类型：
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作者：
Ru, Peng;Steele, Robert;Ray, Ratna B.
前列腺癌仍然是美国男性癌症死亡的第二大原因。早期诊断可提高患者的生存率;然而，晚期疾病的治疗仅限于激素消融技术和姑息治疗。因此，新的治疗方法对于抑制前列腺癌疾病进展是必要的。在这里，我们已经表明，与永生化前列腺上皮细胞相比，miRNA-29 b（miR-29 b）在前列腺癌细胞（PC 3和LNCaP）中的表达较低。在这两种前列腺癌细胞系中，转移性前列腺癌PC 3细胞显示较低的miR-29 b表达。我们还观察到，与患者匹配的非肿瘤组织相比，miR-29 b在人前列腺癌组织中的表达显著下调。异位表达miR-29 b的PC 3细胞抑制伤口愈合、侵袭性，并且在静脉注射后未能在严重联合免疫缺陷小鼠的肺和肝脏中定殖，而表达对照miRNA的PC 3细胞显示转移。与表达对照miRNA的细胞相比，转染miR-29 b的前列腺癌细胞中上皮细胞标志物E-cadherin的表达增强。另一方面，在表达miR-29 b的PC 3细胞中，N-cadherin、Twist和Snail表达下调。这些结果共同表明，miR-29 b在转移级联的多个步骤中作为前列腺癌细胞的抗转移miRNA。因此，miR-29 b可能是前列腺癌治疗干预的潜在新靶点。Mol Cancer Ther; 11（5）; 1166-73. (c)2012年AACR。
Prostate cancer remains the second leading cause of cancer deaths among American men. Early diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared with patient-matched nontumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of severe combined immuno-deficient mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared with cells expressing control miRNA. On the other hand, N-cadherin, Twist, and Snail expression was downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer. Mol Cancer Ther; 11(5); 1166-73. (c) 2012 AACR.