Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 2000127, China.
Biochemistry (Mosc). 2015 Mar;80(3):276-83. doi: 10.1134/S0006297915030037.
Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi-1, a member of PcG family of proteins, has been implicated in the pathogenesis of prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this study, we screened 18 miRNAs that potentially repress the expression of Bmi-1 using a dual luciferase system and found that 12 miRNAs could bind with the 3'-untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR-221, -15a, and -30d was significantly reduced in prostate cancer tissues. Subsequent functional study indicated that miR-221 and miR-30d can repress prostate cancer cell proliferation, and this effect can be partially rescued by Bmi-1 overexpression. Our study constructs the relation between downregulated miR-221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer.
前列腺癌是男性癌症相关死亡的第二大主要原因。Bmi-1 是 PcG 蛋白家族的成员之一，其与前列腺癌的发病机制有关，并且在前列腺癌组织中发现了 miRNA（miRNA）的失调谱。Bmi-1 是如何被 miRNA 调节的尚不清楚。在这项研究中，我们使用双荧光素酶系统筛选了 18 种可能抑制 Bmi-1 表达的 miRNA，发现有 12 种 miRNA 可以与 Bmi-1 mRNA 的 3'非翻译区结合。通过 qRT-PCR，我们发现 miR-221、-15a 和 -30d 在前列腺癌组织中的表达明显降低。随后的功能研究表明，miR-221 和 miR-30d 可以抑制前列腺癌细胞增殖，而过表达 Bmi-1 可以部分挽救这种作用。我们的研究构建了下调的 miR-221 和 miR-30d 与前列腺癌发病机制之间的关系。这些结果表明，miR-221 和 miR-30d 是前列腺癌的候选肿瘤抑制 miRNA，因此可作为人类前列腺癌潜在的临床分类标志物和治疗靶点。
