Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun 130041, China.
Jilin Engineering Laboratory for Translational Medicine of Hepatobiliary and Pancreatic Diseases, The Second Hospital of Jilin University, Changchun 130041, China.
Biomed Res Int. 2018 Aug 29;2018:1431396. doi: 10.1155/2018/1431396. eCollection 2018.
Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. 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 that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. 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. 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. Overall, the study provides support for the possible mechanisms of progression in HCC.
肝细胞癌（HCC）占肝癌的很大比例，已成为全球癌症相关死亡的第二大常见原因。为了研究 HCC 侵袭和进展的潜在机制，我们进行了生物信息学分析，并通过 qRT-PCR 进行了验证。我们发现了 237 个差异表达基因（DEGs），包括 EGR1、FOS 和 FOSB，它们是三个与癌症相关的转录因子。随后，我们基于 mRNA 和 miRNA 表达谱的数据构建了 TF-基因网络和 miRNA-TF-mRNA 网络，以分析 HCC。我们发现 TF-基因网络中的 42 个关键基因，包括 EGR1、FOS 和 FOSB，在 p53 信号通路中最为丰富。qRT-PCR 数据证实，HCC 组织中 EGR1、FOS 和 FOSB 的 mRNA 水平均降低。此外，我们通过生物信息学分析和 qRT-PCR 验证证实，p53 信号通路的三个关键标志物 CCNB1、CCNB2 和 CHEK1 的 mRNA 水平在 HCC 组织中均升高。因此，我们推测 HCC 组织中上调的 miR-181a-5p 可能通过 p53 信号通路调节 FOS 和 EGR1，从而促进 HCC 的侵袭和进展。总体而言，该研究为 HCC 进展的可能机制提供了支持。
