NCBI-GEO is a free database of microarray/gene profile and next-generation sequencing, from which HCC and adjacent nontumor tissue gene expression profile of GSE84402, GSE33006, GSE84005, GSE12941, and GSE64632 were obtained. Microarray Data Information and DEGs Identification This study could provide insightful information and the valuable clue for biomarker discovery and novel treatment strategy in HCC. In addition, we screened differentially expressed TFs in HCC, constructed miRNA-TF-mRNA networks, and proposed a potential miRNA-TF-signaling pathway axis, which identified a systematic exposition of the relevant transcriptional regulation modes associated with invasion and progression of HCC. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to reveal the interaction relationship between DEGs and DEMs and to explore the underlying molecular mechanisms in the carcinogenesis and progression of HCC. Even so, more research is still needed to explore the specific role of different TFs in the progression of HCC.ĭuring the present study, we analyzed 4 mRNA microarray datasets and 1 miRNA microarray dataset from Gene Expression Omnibus (GEO) to obtain DEGs and differentially expressed miRNAs (DEMs) between HCC tissues and adjacent noncancerous tissues by GEO2R. Another research reported that NF κB/EGR1 signaling pathway induced miR-3928v to promote the progression of HCC. found that ETS1, a cancer-related TF, could through interaction with miR-139-5p inhibit cell proliferation, migration, and invasion in HCC. As an important part of participating in life activities, transcription factors (TFs) have been reported to play an important role in the development of HCC by numerous studies. By bioinformatics analysis and microarray technology, functions of some differentially expressed genes (DEGs) in HCC have been explored, which paved the way for exploring complicated process in the occurrence and development of HCC. Over the last decades, bioinformatics and microarray technology have been widely used to screen the molecular mechanisms of HCC, which provide powerful research support for the diagnosis and treatment of HCC. It is significant to investigate the underlying mechanisms of HCC invasion and progression to develop effective diagnostic and therapeutic strategy. Although there is extensive research about the therapies for HCC, the specific mechanisms of HCC occurrence and development were not clear. There are more than 466,100 estimated new cases and 422,100 estimated death cases every year in China. Hepatocellular carcinoma (HCC) is one of the common digestive system malignancies with high mortality, which has become the second most common cause of cancer-related mortality worldwide. Overall, the study provides support for the possible mechanisms of progression in HCC. Therefore, we speculated that miR-181a-5p, which was upregulated in HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression of HCC by p53 signaling pathway. In addition, we confirmed that the mRNA levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR validation. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. We found that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide.
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