Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing 100191, China.
Chin Med J (Engl). 2012 Dec;125(23):4270-6.
Cervical cancer is one of the most common malignant tumors in women. This study was designed to explore the expression profiles of microRNAs (miRNAs) and mRNAs and the gene regulation network in cervical tumorigenesis and to find candidate molecular markers and key tumorigenic genes in cervical cancer.
miRNAs and mRNAs expression microarrays were used to detect the expression of miRNAs and mRNAs in normal and cancer cervical tissues. TargetScan 5.0 database (UK) was used to predict the target genes of the miRNAs, analyze their intersection with differentially expressed mRNAs and negatively correlate the intersection with miRNAs. Bioinformatic approaches were used to analyze functions and pathways of the target genes and establish miRNA-gene network.
Twenty-nine miRNAs and 2036 mRNAs were differentially expressed in normal and cervical tumor tissues. Among them, 13 miRNAs and 754 mRNAs were up-regulated in cervical tumor tissues and 16 miRNAs and 1282 RNA were down-regulated. The 327 target genes negatively related to miRNAs in the intersection were involved in functions and signal pathways. Down-regulated miRNAs targeted genes and up-regulated miRNAs targeted genes were involved in 415 and 163 functions, respectively, and in 37 and 17 significant pathways, respectively (P < 0.05, false discovery rate (FDR) < 0.05). We constructed the miRNAs-gene network and found that hsa-miR-15a, hsa-miR-106b and hsa-miR-20b were key nodes in the network.
The differentially expressed miRNAs and mRNAs in cervical cancer and related miRNA-gene network have been identified. They play important roles in cervical tumorigenesis and are involved in many important biological functions and signal transduction pathways. These findings lay a foundation for research on the molecular mechanism of miRNAs in the pathogenesis of cervical cancer.
宫颈癌是女性最常见的恶性肿瘤之一。本研究旨在探讨宫颈癌发生过程中微小 RNA（miRNA）和 mRNA 的表达谱及基因调控网络，寻找宫颈癌候选分子标志物和关键致癌基因。
采用 miRNA 和 mRNA 表达谱芯片检测正常宫颈组织和宫颈癌组织中 miRNA 和 mRNA 的表达，利用 UK 数据库 TargetScan 5.0 预测 miRNA 的靶基因，分析差异表达的 mRNAs 与靶基因的交集，并与 miRNA 进行负相关分析。采用生物信息学方法分析靶基因的功能和通路，构建 miRNA-基因网络。
正常宫颈组织和宫颈癌组织中差异表达的 miRNA 有 29 个，mRNA 有 2036 个。其中，宫颈癌组织中上调的 miRNA 有 13 个，mRNA 有 754 个，下调的 miRNA 有 16 个，mRNA 有 1282 个。交集的 327 个与 miRNA 呈负相关的靶基因参与了功能和信号通路。下调的 miRNA 靶基因和上调的 miRNA 靶基因分别参与了 415 个和 163 个功能，分别涉及 37 个和 17 个显著通路（P<0.05，假发现率（FDR）<0.05）。我们构建了 miRNA-基因网络，发现 hsa-miR-15a、hsa-miR-106b 和 hsa-miR-20b 是网络中的关键节点。
鉴定出宫颈癌中差异表达的 miRNA 和 mRNA 及其相关 miRNA-基因网络，它们在宫颈癌的发生中发挥着重要作用，涉及许多重要的生物学功能和信号转导通路。这些发现为研究 miRNA 在宫颈癌发病机制中的分子机制奠定了基础。
