ABSTRACT
DNA topoisomerases (TOPs) are dysregulated in various types of cancer. However, how TOP II-alpha (TOP2A) contributes to hepatocellular carcinoma (HCC) progression remains elusive. Cohort analysis revealed that the increased expression of TOP2A was associated with poor clinical outcomes and TOP2A was significantly upregulated in HCC tissues and cell lines. In vitro, TOP2A expression level is related to cell invasion and migration, which may be due to the alteration of epithelial-mesenchymal transition by the TOP2A. Moreover, we used verteporfin (a Hippo inhibitor) to test how the Hippo pathway promotes the effect of TOP2A on the HCC phenotype and found that TOP2A induces tumor progression through the Hippo pathway. Finally, miR-22-5p inhibited tumor progression by sponging TOP2A.
Subject(s)
Carcinoma, Hepatocellular , DNA Topoisomerases, Type II , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , DNA Topoisomerases, Type II/genetics , DNA Topoisomerases, Type II/metabolism , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Hippo Signaling Pathway/genetics , Hippo Signaling Pathway/physiology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , VerteporfinABSTRACT
Tumors are a class of diseases characterized by altered genetic information and uncontrolled growth. Sequencing technology provide researchers with a better way to explore specific tumor pathogenesis. In recent years, single-cell sequencing technology has shone in tumor research, especially in the study of liver cancer, revealing phenomena that were unexplored by previous studies. Single-cell sequencing (SCS) is a technique for sequencing the cellular genome, transcriptome, epigenome, proteomics, or metabolomics after dissociation of tissues into single cells. Compared with traditional bulk sequencing, single-cell sequencing can dissect human tumors at single-cell resolution, finely delineate different cell types, and reveal the heterogeneity of tumor cells. In view of the diverse pathological types and complex pathogenesis of hepatocellular carcinoma (HCC), the study of the heterogeneity among tumor cells can help improve its clinical diagnosis, treatment and prognostic judgment. On this basis, SCS has revolutionized our understanding of tumor heterogeneity, tumor immune microenvironment, and clonal evolution of tumor cells. This review summarizes the basic process and development of single-cell sequencing technology and its increasing role in the field of hepatocellular carcinoma.