ABSTRACT
Epigenetic changes refer to stable alterations in gene expression with no underlying modifications in the genetic sequence itself. It has become clear that not only gene variations but also epigenetic modifications may contribute to varied diseases, including cancer. This review will provide an overview of how epigenetic factors, including genomic DNA methylation, histone modifications, and miRNA regulation, contribute to hepatocellular carcinoma (HCC) dissemination, invasion, and metastasis. Additionally, the reversal of dysregulated epigenetic changes has emerged as a potential strategy for the treatment of HCC, and we will summarize the latest epigenetic therapies for HCC.
Subject(s)
Humans , Carcinoma, Hepatocellular , Genetics , DNA Methylation , Genetics , Epigenesis, Genetic , Genetics , Liver Neoplasms , Genetics , MicroRNAs , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To establish experimental models for tumor neovascularization and to apply quantitative digital imaging analysis in the study.</p><p><b>METHODS</b>An endothelial tube formation model was established by human umbilical vein endothelial cells (HUVECs). A vasculogenic mimicry model was established by SGC-7901 gastric cancer cell line. Fertilized eggs were used to establish a chorioallantoic membrane angiogenesis model. Using gene transfection experiment, IRX1 tumor suppressor gene was chosen as a therapeutic target. Image Pro Plus (IPP) analysis software was used for digital vascular images analysis with parameters including points, lines, angles and integral absorbance (IA) for the tubular formation or vasculogenic mimicry.</p><p><b>RESULTS</b>Digital image analysis by IPP showed that HUVEC tubular formation was significantly inhibited in IRX1 transfectant, compared with controls. The tubular numbers in three groups were 12.80 +/- 3.83, 29.00 +/- 5.34 and 28.20 +/- 4.32 (P<0.01). The connection points of tubules in three groups were 13.20 +/- 2.59, 25.00 +/- 2.24 and 24.60 +/- 3.21 (P<0.01). The tubular lengths of three groups were (821.5 +/- 12.5), (930.9 +/- 13.5) and (948.4 +/- 18.1) microm (P=0.022). The IA values of PAS stain in three groups were 3606 +/- 363, 14 200 +/- 1251 and 15 043 +/- 1220 (P<0.01). In chick chorioallantoic membrane model, the angular numbers of tubules in three groups were 6.41 +/- 2.60, 10.27 +/- 2.65 and 9.18 +/- 1.99 (P<0.01).</p><p><b>CONCLUSIONS</b>The endothelial tube formation model, vasculogenic mimicry model and chorioallantoic membrane angiogenesis model are useful for gene therapy and drug screening with targeting neoplastic vascularization. Professional image analysis software may greatly facilitate the quantitative analysis of tumor neovascularization.</p>
Subject(s)
Animals , Humans , Cell Line, Tumor , Cells, Cultured , Chorioallantoic Membrane , Diagnostic Imaging , Methods , Homeodomain Proteins , Genetics , Metabolism , Physiology , Human Umbilical Vein Endothelial Cells , Neovascularization, Pathologic , Neovascularization, Physiologic , Software , Stomach Neoplasms , Genetics , Metabolism , Pathology , Transcription Factors , Genetics , Metabolism , Physiology , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To clone core promoter regions of iroquois homeobox gene 1 (IRX1) gene and evaluate the regulatory mechanism of IRX1 transcription.</p><p><b>METHODS</b>Upstream sequence from transcriptional start site was predicted using bioinformatics methods. Serial deleted fragments from IRX1 promoter sequences were amplified by PCR and luciferase reporter plasmids were constructed. The luciferase intensity was analyzed after transferring reporters into GES-1 gastric mucosa cell line.</p><p><b>RESULTS</b>The promoter of IRX1 was predicted to be within 700 bp from the 5'-flanking region of IRX1 gene. Eight serial deleted luciferase reporter plasmids were constructed. The transcriptional activity of different fragments was expressed as following: p-416>p-584>p-715>p-350>p-687>p-320>p-188>p-92. Except p-320 and p-188, the transcriptional activity of other 6 fragments was higher than that of PGL3-basic plasmid. The transcriptional activity was the highest in p-416 and decreased sharply from p-320 to p-188.</p><p><b>CONCLUSIONS</b>The fragment p-416 shows the strongest promoter activity. The sequence from -320 bp to -188 bp is identified as core promoter region, which is focused as key sequence for further regulatory analysis, since some binding sites for important transcriptional factors such as Sp1 and TFII D are predicted.</p>