Investigating the mechanism of hepatocellular carcinoma progression by constructing genetic and epigenetic networks using NGS data identification and big database mining method.
The mechanisms leading to the development and progression of hepatocellular carcinoma (HCC) are complicated and regulated genetically and epigenetically. The recent advancement in high-throughput sequencing has facilitated investigations into the role of genetic and epigenetic regulations in hepatocarcinogenesis. Therefore, we used systems biology and big database mining to construct genetic and epigenetic networks (GENs) using the information about mRNA, miRNA, and methylation profiles of HCC patients. Our approach involves analyzing gene regulatory networks (GRNs), protein-protein networks (PPINs), and epigenetic networks at different stages of hepatocarcinogenesis. The core GENs, influencing each stage of HCC, were extracted via principal network projection (PNP). The pathways during different stages of HCC were compared. We observed that extracellular signals were further transduced to transcription factors (TFs), resulting in the aberrant regulation of their target genes, in turn inducing mechanisms that are responsible for HCC progression, including cell proliferation, anti-apoptosis, aberrant cell cycle, cell survival, and metastasis. We also selected potential multiple drugs specific to prominent epigenetic network markers of each stage of HCC: lestaurtinib, dinaciclib, and perifosine against the NTRK2, MYC, and AKT1 markers influencing HCC progression from stage I to stage II; celecoxib, axitinib, and vinblastine against the DDIT3, PDGFB, and JUN markers influencing HCC progression from stage II to stage III; and atiprimod, celastrol, and bortezomib against STAT3, IL1B, and NFKB1 markers influencing HCC progression from stage III to stage IV.
Laboratory of Control and Systems Biology, National Tsing Hua University, Hsinchu, Taiwan.
Cheng-Wei
CW
Li
Laboratory of Control and Systems Biology, National Tsing Hua University, Hsinchu, Taiwan.
Ping-Yao
PY
Chang
Laboratory of Control and Systems Biology, National Tsing Hua University, Hsinchu, Taiwan.
Bor-Sen
BS
Chen
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology / Q000379:methods*; D019175:DNA Methylation; D057225:Data Mining; D018450:Disease Progression; D044127:Epigenesis, Genetic; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D009367:Neoplasm Staging; D017422:Sequence Analysis, DNA; D049490:Systems Biology
D035683:MicroRNAs
DNA methylation; hepatocarcinogenesis; miRNAs; multiple potential drugs; principal network projection