MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer.
MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer.
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DOI：
10.1093/nar/gkr1222
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发表时间：
2012-04
影响因子：
14.9
通讯作者：
Ambs S
中科院分区：
文献类型：
--
作者：
Hudson RS;Yi M;Esposito D;Watkins SK;Hurwitz AA;Yfantis HG;Lee DH;Borin JF;Naslund MJ;Alexander RB;Dorsey TH;Stephens RM;Croce CM;Ambs S
我们之前报道过，miR-1是原发性人类前列腺肿瘤中最一致下调的mir之一。在这项后续研究中，我们在一个独立的数据集中进一步证实了这一发现，并提出了新的观察结果，即miR-1的表达在远处转移中进一步降低，是疾病复发的候选预测因子。此外，我们还进行了体外实验来探索miR-1的肿瘤抑制功能。基于细胞的分析表明，miR-1在人类前列腺癌中是表观遗传沉默的。miR-1在这些细胞中的过度表达导致生长抑制和调控细胞周期进程、有丝分裂、DNA复制/修复和肌动蛋白动力学的基因下调。蛋白表达分析和基于3′- utr的报告基因实验进一步证实了这一观察结果，表明这些通路中的基因是miR-1的直接或间接靶点。一项基因集富集分析显示，mir -1介导的肿瘤抑制作用与组蛋白去乙酰化酶抑制剂在全球范围内相似。最后，我们获得了初步证据，证明miR-1可以改变F-actin的细胞组织，抑制肿瘤细胞的侵袭和filipodia的形成。总之，我们的研究结果表明，miR-1通过影响多种癌症相关过程和抑制细胞增殖和运动，在前列腺癌中发挥肿瘤抑制作用。
We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent data set and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a candidate predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair and actin dynamics. This observation was further corroborated with protein expression analysis and 3′-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that the miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters the cellular organization of F-actin and inhibits tumor cell invasion and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
4.3
作者：
Day CP;Carter J;Bonomi C;Esposito D;Crise B;Ortiz-Conde B;Hollingshead M;Merlino G
通讯作者：
Merlino G
影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
64.5
作者：
Mayr C;Bartel DP
通讯作者：
Bartel DP