Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma.

Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

Tumor-Promoting Effects of Microrna-421/4-Aminobutyrate Aminotransferase Axis in Hepatocellular Carcinoma

ABSTRACT Background: MicroRNA-421 (miR-421) has been implicated in hepatocellular carcinoma (HCC), but its potential mechanism in HCC remains unclear. Objectives: The study aimed to study the potential mechanism of miR-421 in HCC which is necessary. Methods: The downstream target genes of miR-421 were screened in HCC tissues and cells using miDIP, Targetscan, and starBase databases. Differential analysis, survival analysis, and Pearson correlation analysis were performed between miR-421 and its downstream target genes. Quantitative reverse transcription polymerase chain reaction and western blot were used to assay RNA and protein levels of 4-aminobutyrate aminotransferase (ABAT) and epithelial-mesenchymal transition (EMT)-related proteins. Cell-based assays, including CCK-8, wound healing, transwell, flow cytometry, and metabolic measurements, were implemented to assess proliferation, migration, invasion, cell cycle, and apoptosis of HCC cells with different treatments. Dual-luciferase assay was utilized to detect the targeting relationship between miR-421 and ABAT. Results: miR-421 level was elevated in HCC tissues and cells, and low miR-421 expression hindered phenotype progression of HCC cells. ABAT was identified as a direct target of miR-421 in HCC cells, and miR-421 could inhibit ABAT expression. Rescue assay revealed that miR-421 promoted HCC cell tumorigenesis progress and affected cell metabolic remodeling through down-regulating ABAT. Conclusion: The miR-421/ABAT regulatory axis promoted HCC cell tumorigenesis progress, highlighting its potential as a therapeutic target for HCC.

Effect of chemokine CXCL14 on in vitro angiogenesis of human hepatocellular carcinoma cells.

The study was designed to investigate the effect of chemokine CXCL14 on in vitro angiogenesis of human hepatocellular carcinoma (HCC) cells. CXCL14 mRNA expression in HCC tissue samples and adjacent tissue samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). CXCL14 mRNA and protein expression in human normal hepatocyte HL-7702 and HCC cell line HepG2 were detected by qRT-PCR and western blot. In HepG2 cell line, the expression of vascular endothelial growth factor (VEGF) was detected by enzyme-linked immunosorbent assay method, cell viability was detected by CCK-8, cell proliferation was detected by colony formation assay, and cell migration as well as invasion ability was detected by Transwell assay. Moreover, human umbilical vein endothelial cell (HUVEC) tube formation assay was carried out to determine the cell ability of angiogenesis. Results showed that the overexpression of CXCL14 could inhibit angiogenesis, proliferation, migration, and invasion abilities of HCC cells.Highlights CXCL14 is lowly expressed in hepatocellular carcinoma tissues and cells. CXCL14 overexpression inhibits the angiogenesis of hepatocellular carcinoma cells. CXCL14 overexpression inhibits proliferation, invasion, and migration of hepatocellular carcinoma cells.

Identifying 13 Hub Genes Associated with Progression and Prognosis of Hepatocellular Carcinoma with Weighted Gene Co-Expression Network Analysis.

Hepatocellular carcinoma (HCC) is a type of common cancer, often accompanied by tumor recurrence and metastasis after surgery with poor prognosis. Therefore, searching into potential biomarkers that can effectively predict the prognosis and progression of HCC is crucial. In this study, we identified 1,981 differentially expressed genes (DEGs) using mRNA expression profiles from the TCGA-LIHC dataset. Subsequently, weighted gene co-expression network analysis found that the turquoise module closely associated with the pathological grade and clinical stage of HCC was identified. Then, from the key genes in the turquoise module and protein-protein interaction network analysis, 13 hub genes significantly related to the prognosis of HCC were screened. Through co-expression and functional enrichment analyses, these 13 hub genes were found to play an important role in mitosis. Finally, we evaluated the relationship between these hub genes and overall survival and disease-free survival through survival analysis. The result indicated that HCC patients with high hub gene expression had a poorer prognosis than HCC patients with low expression. Receiver operating characteristic curves showed that each hub gene could predict the prognosis of HCC patients. In summary, a total of 13 hub genes were identified that play an important role in the progression of HCC, which can be used as potential biomarkers for HCC patients.

TP53 rs28934571 polymorphism increases the prognostic risk in hepatocellular carcinoma.

Aim: Hepatocellular carcinoma (HCC) is considered to be the third leading cause of cancer death. The homologous gene of TP53 is significant in the occurrence and development of cancer. This study explored the relationship between TP53 rs28934571 polymorphism and HCC risk in Guangxi, China. Materials & methods: We first screened the association through bioinformatics. Additionally, a case-control study was performed to further verify the relationship between gene polymorphism and HCC risk after collecting clinical characteristics. Results: Results showed that allele A on TP53 rs28934571 was a risk factor for HCC and mutation from C to A on TP53 rs28934571 would increase the risk of poor prognosis of HCC. Conclusion: Therefore, the study concluded that TP53 rs28934571 may become a diagnostic indicator in judging the prognosis of HCC.

MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F7.

OBJECTIVE: This study aims to explore the mechanism of the miR-424-5p/E2F7 axis in hepatocellular carcinoma (HCC) and provide new ideas for targeted therapy of HCC. METHODS: Bioinformatics analysis was used to identify the target differentially expressed miRNA in HCC and predict its target gene. qRT-PCR was employed to verify the expression of miR-424-5p and E2F7 mRNA in HCC cells. Western blot was performed to detect the effect of miR-424-5p ectopic expression on the protein expression of E2F7. CCK-8 was used to detect proliferative activity of HCC cells and flow cytometry was carried out for analyzing cell cycle distribution. Dual luciferase reporter assay was conducted to verify the direct targeting relationship between miR-424-5p and E2F7. RESULTS: We observed that miR-424-5p was down-regulated in HCC cells. CCK-8 showed that overexpression of miR-424-5p inhibited cell proliferation, and flow cytometry showed that miR-424-5p could block cells in G0/G1 phase. E2F7 was up-regulated in HCC cells, and E2F7 overexpression could facilitate the proliferative ability of HCC cells and promote the cell cycle progressing from G0/G1 to S phase. Furthermore, dual-luciferase reporter assay indicated that miR-424-5p could directly down-regulate E2F7 expression. Analysis on cell function demonstrated that miR-424-5p inhibited the proliferation of HCC cells and blocked cell cycle at G0/G1 phase by targeting E2F7. CONCLUSION: Our results proved that E2F7 was a direct target of miR-424-5p, and miR-424-5p could regulate cell cycle and further inhibit the proliferation of HCC cells by targeting E2F7.

Speeding Up the Write Operation for Multi-Level Cell Phase Change Memory with Programmable Ramp-Down Current Pulses.

Multi-level cell (MLC) phase change memory (PCM) can not only effectively multiply the memory capacity while maintaining the cell area, but also has infinite potential in the application of the artificial neural network. The write and verify scheme is usually adopted to reduce the impact of device-to-device variability at the expense of a greater operation time and more power consumption. This paper proposes a novel write operation for multi-level cell phase change memory: Programmable ramp-down current pulses are utilized to program the RESET initialized memory cells to the expected resistance levels. In addition, a fully differential read circuit with an optional reference current source is employed to complete the readout operation. Eventually, a 2-bit/cell phase change memory chip is presented with a more efficient write operation of a single current pulse and a read access time of 65 ns. Some experiments are implemented to demonstrate the resistance distribution and the drift.