Integrative network analysis reveals active microRNAs and their functions in gastric cancer.
Integrative network analysis reveals active microRNAs and their functions in gastric cancer.
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综合网络分析揭示了主动microRNA及其在胃癌中的功能。
DOI：
10.1186/1752-0509-5-99
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发表时间：
2011-06-26
影响因子：
--
通讯作者：
Juan HF
中科院分区：
文献类型：
--
作者：
Tseng CW;Lin CC;Chen CN;Huang HC;Juan HF
MicroRNA (miRNA) 是一类内源性、小型且高度保守的非编码 RNA，可通过降解靶 mRNA 或抑制蛋白质翻译来控制基因表达。它们在癌症进展中发挥着重要作用。单个 miRNA 可以引发连锁反应并进一步影响蛋白质相互作用网络 (PIN)。因此，我们开发了一种新颖的综合方法来识别 oncomir 的功能作用和受监管的 PIN。我们将 miRNA 和 mRNA 的表达谱与人类 PIN 相结合，以揭示特定生物条件下 miRNA 调节的 PIN。通过功能富集分析确定 miRNA 的潜在功能，并通过蛋白质-蛋白质相互作用 (PPI) 的共表达评估 miRNA 调节的 PIN 的活性。通过临床数据分析和细胞实验进一步检查了特定 miRNA miR-148a 的功能。我们发现了几个 miRNA 调控的网络，这些网络富含与癌症进展相关的功能。鉴定出一种 miRNA，miR-148a，其功能是通过其调节的 PIN 来减少肿瘤增殖和转移。此外，我们发现miR-148a可以降低胃肿瘤细胞的侵袭性、迁移性和粘附活性。最重要的是，胃癌组织中miR-148a水平升高与远处转移、器官和腹膜侵袭以及生存率降低密切相关。这项研究提供了一种识别活性癌瘤及其在胃癌进展中的潜在功能的新方法。目前的数据表明，miR-148a 可能是胃癌的潜在预后生物标志物，并通过抑制其调节的 PIN 的活性发挥肿瘤抑制因子的作用。
MicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs. We integrated the expression profiles of miRNA and mRNA with the human PIN to reveal miRNA-regulated PIN in specific biological conditions. The potential functions of miRNAs were determined by functional enrichment analysis and the activities of miRNA-regulated PINs were evaluated by the co-expression of protein-protein interactions (PPIs). The function of a specific miRNA, miR-148a, was further examined by clinical data analysis and cell-based experiments. We uncovered several miRNA-regulated networks which were enriched with functions related to cancer progression. One miRNA, miR-148a, was identified and its function is to decrease tumor proliferation and metastasis through its regulated PIN. Furthermore, we found that miR-148a could reduce the invasiveness, migratory and adhesive activities of gastric tumor cells. Most importantly, elevated miR-148a level in gastric cancer tissues was strongly correlated with distant metastasis, organ and peritoneal invasion and reduced survival rate. This study provides a novel method to identify active oncomirs and their potential functions in gastric cancer progression. The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN.
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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.
DOI：
10.1073/pnas.0402088101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Koike, T;Kimura, N;Kanangi, R
通讯作者：
Kanangi, R
影响因子：
11.2
作者：
Landemaine, Thomas;Jackson, Amanda;Driouch, Keltouma
通讯作者：
Driouch, Keltouma
影响因子：
29.4
作者：
Meng, Fanyin;Henson, Roger;Patel, Tushar
通讯作者：
Patel, Tushar
影响因子：
3.4
作者：
Hsu, Chun-Wei;Juan, Hsueh-Fen;Huang, Hsuan-Cheng
通讯作者：
Huang, Hsuan-Cheng