MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing.
MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing.
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下一代小 RNA 测序揭示阴茎癌中的 MicroRNA 表达谱。
DOI：
10.1371/journal.pone.0131336
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liang C
中科院分区：
文献类型：
--
作者：
Zhang L;Wei P;Shen X;Zhang Y;Xu B;Zhou J;Fan S;Hao Z;Shi H;Zhang X;Kong R;Xu L;Gao J;Zou D;Liang C
阴茎癌(Peca)是一种相对罕见的肿瘤，但发病率和死亡率较高，尤其是在发展中国家。到目前为止，参与Peca肿瘤发生和发展的具体致病信号通路和核心机制仍有待阐明。一些研究表明，在转录后水平调节基因表达的miRNAs在人类癌症中经常被错误调控和异常表达。然而，人类Peca中的miRNA图谱以前没有报道过。在本研究中，通过下一代测序，从10例新鲜阴茎癌组织和匹配的邻近非癌组织中获得了miRNA图谱。结果，在正常和癌变的阴茎组织中分别发现了751个和806个带注释的miRNAs。其中56个miRNAs在配对组织中的表达水平存在显著差异。随后，随机选择了几个带注释的miRNAs，并用实时定量聚合酶链式反应进行了验证。与以往关于miRNAs在各种癌症，特别是泌尿生殖系(前列腺癌、膀胱癌、肾癌、睾丸癌)中表达变化的文献相比，大多数解除调控的miRNAs在阴茎癌中的表达模式相似。此外，生物信息学分析表明，癌组织和匹配的正常阴茎组织中差异表达的miRNAs的靶基因可能通过调节Wnt、MAPK、P53、PI3K-Akt、Notch和转化生长因子-β信号通路而与细胞连接、增殖、生长和基因组不稳定性等密切相关，这些信号通路都参与了肿瘤的发生和发展。我们的工作提供了一个差异表达的miRNAs及其靶基因潜在调控网络的全球视角，以阐明正常阴茎向PecA的致病转化，这一研究资源也为未来旨在探索miRNAs和包括piRNAs在内的其他小RNAs在阴茎癌变调控和有效的靶向特异性治疗中的深入机制的研究提供了新的见解。
Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis.
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影响因子：
3.7
作者：
Calmon MF;Mota MT;Babeto É;Candido NM;Girol AP;Mendiburu CF;Bonilha JL;Silvestre RV;Rosa BM;Thomé JA;Medeiros GH;Soares FA;Guimarães GC;de Arruda JG;Oliani SM;Villa LL;Vassallo J;Rahal P
通讯作者：
Rahal P
影响因子：
11.2
作者：
Chen, Hsin-Yi;Lin, Yu-Min;Chen, Ruey-Hwa
通讯作者：
Chen, Ruey-Hwa
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ