Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer.
Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer.
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DOI：
10.1038/bjc.2017.191
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发表时间：
2017-07-25
影响因子：
8.8
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Goto Y;Kurozumi A;Arai T;Nohata N;Kojima S;Okato A;Kato M;Yamazaki K;Ishida Y;Naya Y;Ichikawa T;Seki N
尽管最近取得了进展，但转移性去势抵抗性前列腺癌（CRPC）仍不被认为是可治愈的。需要新的方法来鉴定CRPC的治疗靶点。下一代测序显示每个致死mCRPC样本中有945-1248个mirna。我们通过比较CRPC与正常前列腺组织或激素敏感前列腺癌（HSPC）的miRNA表达，构建了CRPC的miRNA表达特征。研究人员进行了全基因组基因表达研究和计算机分析，以预测miRNA调控，并研究这些miRNA调控的新型致癌途径在前列腺癌（PCa）中的功能意义和临床应用。基于CRPC新的miRNA表达特征，miR-145-5p和miR-145-3p在CRPC中下调。通过关注miR-145-3p，这是一种客运链，在之前的报道中没有得到很好的研究，我们发现miR-145-3p在CPRC中靶向4个关键分子，即MELK， NCAPG， BUB1和CDK1。这4个基因显著预测PCa患者的生存。致死性CRPC的小RNA测序和计算机分析为CRPC提供了新的治疗靶点。
Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. Next-generation sequencing revealed 945–1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC). Genome-wide gene expression studies and in silico analyses were carried out to predict miRNA regulation and investigate the functional significance and clinical utility of the novel oncogenic pathways regulated by these miRNAs in prostate cancer (PCa). Based on the novel miRNA expression signature of CRPC, miR-145-5p and miR-145-3p were downregulated in CRPC. By focusing on miR-145-3p, which is a passenger strand and has not been well studied in previous reports, we showed that miR-145-3p targeted 4 key molecules, i.e., MELK, NCAPG, BUB1, and CDK1, in CPRC. These 4 genes significantly predicted survival in patients with PCa. Small RNA sequencing for lethal CRPC and in silico analyses provided novel therapeutic targets for CRPC.
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影响因子：
8.8
作者：
Goto Y;Kojima S;Kurozumi A;Kato M;Okato A;Matsushita R;Ichikawa T;Seki N
通讯作者：
Seki N
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A