Angiogenesis by Tumor Cells in Hepatocellular Carcinoma

17 Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, 18 metastasis accounts for most of the cases. Angiogenesis plays an important role in 19 cancer metastasis, but how tumor cells affect the function of endothelial cells by 20 dictating their miRNA expression remains largely unknown. 21 Differentially expressed miRNAs (DEMs) were identified through dataset downloaded 22 from the Gene Expression Omnibus (GEO) database and analyzed by GEO2R. We then 23 use online tools to obtain potential targets of candidate microRNAs(miRNAs) and 24 functional enrichment analysis,as well as the protein-protein interaction (PPI). Finally, 25 the function of miR-302c-3p was validated through in vitro assay. 26 In the current study, we found that HCC cells altered miRNAs expression profiles of 27 D ow naded rom http://pndpress.com /bioscirep/adf/doi/10.1042/BSR 20210126/9/bsr-2021-0126.pdf by gest on 29 June 2021 Biocience R eorts. This is an Acepted M ancript. ou re encuraged to se he Vrsion of R eord tat, w en puished, w ill relace his vesion. he m st up-tote-version is avilable at https://dg/10.1042/BSR 2010126 Regulation of Angiogenesis in HCC human umbilical vein endothelial cells (HUVECs) and miR-302c-3p was the most 28 downregulated miRNA in HUVECs when they were co-cultured with HCC-LM3 cells. 29 Functional enrichment analysis of the candidate targets revealed that these genes were 30 involved in epigenetic regulation of gene expression, in particular, histone methylation. 31 In addition, PPI network demonstrated distinct roles of genes targeted by miR-302c-3p. 32 Importantly, inhibition of angiogenesis, migration and permeability by the most 33 downregulated miR-302c-3p in HUVECs was confirmed in vitro. These findings 34 brought us novel insight into the regulation of angiogenesis by HCC cells and provided 35 potential targets for the development of therapeutic strategies. 36