MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation
MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation
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DOI：
10.1038/onc.2009.192
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发表时间：
2009-09-24
期刊：
影响因子：
8
通讯作者：
Lu, P-J
中科院分区：
文献类型：
--
作者：
Lee, K-H;Chen, Y-L;Lu, P-J
微小RNA（miRNA）构成了一类新型基因调节因子;它们通过靶向肿瘤抑制基因或癌基因而发挥癌基因或肿瘤抑制基因的作用。最近一项分析了大量人类癌细胞系的研究表明，miR-330是一种潜在的肿瘤抑制基因。然而，miR-330在决定人类前列腺癌侵袭性中的功能和分子机制尚未研究。在这里，我们发现miR-330在人前列腺癌细胞系中的表达显著低于非致瘤性前列腺上皮细胞。生物信息学分析揭示了miR-330在E2 F1的3 '-非翻译区（UTR）的核苷酸1018-1024处的保守靶位点。MiR-330显著抑制细胞中含有E2 F1 - 3 '-UTR的荧光素酶报告基因的活性。这种活性可以用抗miR-330或突变的E2 F1 - 3 '-UTR的转染来消除。此外，miR-330和E2 F1的表达水平在细胞系和前列腺癌标本中呈负相关。在PC-3细胞中过表达miR-330后，细胞生长通过减少E2 F1介导的Akt磷酸化而受到抑制，从而诱导细胞凋亡。总的来说，这是第一项研究表明E2 F1受miR-330的负调控，也表明miR-330通过E2 F1介导的Akt磷酸化抑制诱导前列腺癌细胞凋亡。Oncogene（2009）28，3360-3370; doi：10.1038/onc.2009.192; 2009年7月13日在线发表
MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molecular mechanism of miR-330 in determining the aggressiveness of human prostate cancer has not been studied. Here, we show that miR-330 is significantly lower expressed in human prostate cancer cell lines than in nontumorigenic prostate epithelial cells. Bioinformatics analyses reveal a conserved target site for miR-330 in the 3'-untranslated region (UTR) of E2F1 at nucleotides 1018-1024. MiR-330 significantly suppressed the activity of a luciferase reporter containing the E2F1-3'-UTR in the cells. This activity could be abolished with the transfection of anti-miR-330 or mutated E2F1-3'-UTR. In addition, the expression level of miR-330 and E2F1 was inversely correlated in cell lines and prostate cancer specimens. After overexpressing of miR-330 in PC-3 cells, cell growth was suppressed by reducing E2F1-mediated Akt phosphorylation and thereby inducing apoptosis. Collectively, this is the first study to show that E2F1 is negatively regulated by miR-330 and also show that miR-330 induces apoptosis in prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation. Oncogene (2009) 28, 3360-3370; doi: 10.1038/onc.2009.192; published online 13 July 2009