Molecular characteristics associated with ferroptosis in hepatocellular carcinoma progression
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RESEARCH ARTICLE
Molecular characteristics associated with ferroptosis in hepatocellular carcinoma progression Zuo Fei1 · Yin Lijuan2 · Zhuang Jing3 · Yang Xi4 · Pan Yuefen4 · Han Shuwen4 Received: 28 June 2020 / Accepted: 8 September 2020 © Japan Human Cell Society 2020
Abstract The aim of this study was to investigate the genes associated with ferroptosis and the progression of hepatocellular carcinoma (HCC). The RNA sequencing data of erastin-induced ferroptosis in HCC cells were downloaded from the Sequence Read Archive database with accession number SRP119173. The microarray dataset GSE89377 of HCC progression was downloaded from the Gene Expression Omnibus database. The ferroptosis-related genes were screened by differential analysis and HCC progression-related genes were screened by cluster analysis using Mfuzz. Then, the genes associated with ferroptosis and HCC progression were screened by Venn analysis, followed by functional enrichment, protein–protein interaction (PPI) analysis, and transcription factor (TF) prediction. Finally, survival analysis was performed using data from the Cancer Genome Atlas database. A total of 33 upregulated and 52 downregulated genes associated with HCC progression and ferroptosis were obtained, and these genes were significantly involved in the negative regulation of ERK1 and ERK2 cascades; the NAD biosynthetic process; alanine, aspartate, and glutamate metabolism; and other pathways. The PPI network contained 52 genes and 78 interactions, of which, cell division cycle 20 (CDC20) and heat shock protein family B (small) member 1 (HSPB1) were hub genes found in higher degrees. Among the 85 genes associated with HCC progression and ferroptosis, two TFs (activating TF 3 (ATF3) and HLF) were predicted, with HSPB1 targeted by ATF3. In addition, 26 genes that were found to be significantly correlated with the overall survival of HCC patients were screened, including CDC20 and thyroid hormone receptor interactor 13. Several genes associated with HCC progression and ferroptosis were screened based on a comprehensive bioinformatics analysis. These genes played roles in HCC progression and ferroptosis via the negative regulation of the ERK1 and ERK2 cascades; the NAD biosynthetic process; and alanine, aspartate, and glutamate metabolism. ATF3 and HSPB1 played important roles in HCC progression and ferroptosis, with HSPB1 possibly regulated by ATF3. Keywords Ferroptosis · Hepatocellular carcinoma · Overall survival · Heat shock protein family B member 1 · Activating transcription factor 3
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00431-w) contains supplementary material, which is available to authorized users. * Han Shuwen [email protected] Zuo Fei [email protected] Yin Lijuan [email protected] Zhuang Jing [email protected] Yang Xi [email protected] Pan Yuefen [email protected]
1
Department of Gastroenterology, Huzhou Cent Hospital, Affiliated Cent Hospital HuZhou University, 198 Hongqi Rd, H
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