Identification and Functional Analysis of Enhancers-regulated miRNA Feed-forward Loops in Hepatocellular Carcinoma

doi:10.13560/j.cnki.biotech.bull.1985.2018-0846

Abstract

Abstract: Previous studies demonstrate that,as an important network motif,feed-forward loops（FFLs）play an important role in the development of tumor diseases. Three types of elements,namely miRNAs,enhancers,and transcription factors,are widely reported to be closely related to tumors. However,the characteristics of the FFLs and their function in hepatocellular carcinoma remain unclear. Here 5055 liver cancer-specific enhancers were identified based on the DNase high-sensitivity site of HepG2 cells and the ChIP-seq data of modification information of 3 three types of histone H3K4me1,H3K27ac and H3K4me3. In addition,2070 TF-enhancer-miRNA FFLs were identified based on hypergeometric test and component regulation relationship. The analysis result of miRNA target genes in FFLs by GO and KEGG functional enrichment showed that target genes of miRNAs in the FFLs were significantly enriched in tumor or hepatocellular carcinoma-related signaling pathways and biological processes. Among them,hsa-miR-574 was involved in 99 FFLs and highly expressed in HepG2 cells,and significantly enriched in the known cAMP signaling pathway in inhibiting the proliferation of hepatoma cells. These results preliminarily explored the characteristics and functions of the enhancer-miRNA-based FFLs in hepatocellular carcinoma,and it is expected to provide a theoretical and data basis for liver tumor marker recognition based on network motif.

Key words: enhancer, miRNA, feed-forward loop, liver cancer, transcription factor

CHANG Yun-jian, KANG Ran, XUE Xuan, WANG Shao-chang, ZHAO Qing-wen, GUO Zhi-yun. Identification and Functional Analysis of Enhancers-regulated miRNA Feed-forward Loops in Hepatocellular Carcinoma[J]. Biotechnology Bulletin, 2019, 35(5): 140-145.

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