| 郭鹏展,刘 畅,刘世杰,孙晓媚,石雁梅.肝内胆管细胞癌与肝细胞癌miRNA相关级联调控网络及通路研究[J].现代生物医学进展英文版,2018,(2):309-315. |
| 肝内胆管细胞癌与肝细胞癌miRNA相关级联调控网络及通路研究 |
| MiRNA Associated Regulatory Network and Pathway Analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma |
| Received:November 21, 2017 Revised:December 13, 2017 |
| DOI：10.13241/j.cnki.pmb.2018.02.026 |
| 中文关键词: 肝内胆管细胞癌 肝细胞癌 乙型肝炎 级联调控网络 级联调控通路 |
| 英文关键词: Intrahepatic cholangiocarcinoma Hepatocellular carcinoma Hepatitis B virus Cascade regulatory network Cascade regulatory pathway |
| 基金项目:黑龙江省教育厅科学技术研究面上项目（11541214） |
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| 中文摘要: |
| 摘要 目的：分析肝内胆管细胞癌（ICC）与肝细胞癌（HCC）患者肝组织小非编码RNA（MicroRNAs，miRNA）、转录因子（Transcription factor，TF）和信使RNA（messenger, mRNA）的级联调控网络，探讨关键miRNA和TF相关的级联调控网络以及调控通路的作用。方法：下载GEO（GSE57555）miRNA/mRNA表达谱芯片数据，通过生物信息数据分析方法获得肝细胞癌患者和癌旁组织显著差异的miRNA、mRNA表达谱，并依据现今已知的实验证实的miRNA、TF和靶基因间的调控关系构建级联调控背景网络。通过ICC和HCC各自差异表达的miRNA和mRNA挖掘出疾病特异的级联调控网络。继而分析级联调控网络中的mRNA参与的GO、KEGG以及挖掘网络中重要的级联调控通路识别通路内的关键调控元件。结果：构建的ICC级联调控网络内的度最大的节点主要为miRNA（has-miR-200b-3p、hsa-miR-155-5p），而HCC级联调控网络内度最大的节点为TF，而且网路中包含关键的已知疾病相关基因TP53、CTNNB1，无论是miRNA还是TF都是和相应疾病密切相关的。ICC和HCC级联调控网络中的mRNA主要参与的GO功能有RNA聚合酶Ⅱ的调控、表达调控、凋亡过程调控等；KEGG信号通路主要有癌症相关miRNA通路、乙型肝炎通路、癌症通路等。共挖掘出12条疾病特异的级联调控通路，识别出ICC相关通路内关键的调控因子为MYC、hsa-miR-320b，HCC相关通路内的关键调控因子为hsa-miR-124-3p、HMGA1。结论：TP53、MYC、HMGA1、has-miR-200b-3p、hsa-miR-155-5p和hsa-miR-124-3p为ICC和HCC级联调控网络内的核心调控元件，在ICC和HCC相关的肝细胞癌发生、发展中具有关键作用，有望为未来的ICC和HCC相关研究提供新思路和新方向。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the roles of cascade regulatory networks and cascade regulatory pathways associated with key miRNAs and TFs, we analyzed the cascade regulatory network of small non-coding RNA (miRNA), transcription factor (TF) and messenger RNA (mRNA) in the intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: The miRNA / mRNA microarray data were downloaded from GEO (GSE57555), including surgically resected hepatocellular carcinoma (HCC) samples and surrounded non-tumor samples, and cholangiocarcinoma (CCC) samples and surrounded non-tumor samples. Then using the experiments confirmed regulation relationships between miRNAs, TF and target genes to construct the background cascade regulatory network. Differentially expressed miRNAs and mRNAs were identified in ICC and HCC to discover disease-specific cascade regulatory networks, respectively. Then we performed GO and KEGG enrichment analyses for mRNAs involved in the cascade regulation network. Moreover, we explored the crucial cascade regulatory pathways in the cascade network and identified the key regulators in the cascade regulatory pathways. Results: The node with highest degree in the ICC cascade network was one ICC- related miRNA (hsa-miR-155-5p), and the hub nodes in the HCC cascade network also included one HCC-related TF (TP53). The mRNAs in the ICC and HCC cascade regulation networks were mainly enriched in the biological processes of RNA polymerase II, regulation of expression, regulation of apoptosis process and cancer-related miRNA pathway, hepatitis B pathway and cancer pathway. Finally, 12 disease-specific cascade regulatory pathways were identified. The key regulators of ICC-related pathways were MYC and hsa-miR-320b. The key regulators of HCC-related pathways were hsa-miR-124-3p and HMGA1. Conclusion: TP53, MYC, HMGA1, has-miR-200b-3p, hsa-miR-155-5p and hsa-miR-124-3p were key regulators in the ICC and HCC cascade regulatory networks. They played an important role in the development of hepatocellular carcinoma. This study is expected to provide new ideas and new directions for the future therapeutic strategy of ICC and HCC. |
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