Comprehensive analysis of diverse programmed cell death patterns in the prognosis, tumor microenvironment and drug sensitivity in hepatocellular carcinoma.

Treatment failure in patients with liver hepatocellular carcinoma (LIHC) is primarily caused by tumor progression and therapy resistance. Tumor immunity plays a crucial role in regulating the homeostasis of cells through the process of programmed cell death (PCD). However, the expression profile and clinical significance of PCD-related genes in LIHC require further investigation. In this study, we analyzed twelve commonly observed PCD patterns to construct a prognostic model. We collected RNA-seq data, genomics, and clinical information from TCGA-LIHC and GSE14520 cohorts to validate the prognostic gene signature. We discovered 75 PCD-related differentially expressed genes (DEGs) with prognostic significance in LIHC. Using these genes, we constructed a PCD-related score (PCDscore) with an 11-gene signature through LASSO COX regression analysis. Validation in the GSE14520 cohort demonstrated that LIHC patients with high PCDscore had poorer prognoses. Unsupervised clustering based on the 11 model genes revealed 3 molecular subtypes of LIHC with distinct prognoses. By incorporating PCDscore with clinical features, we constructed a highly predictive nomogram. Additionally, PCDscore was correlated with immune checkpoint genes and immune cell infiltration. LIHC patients with high PCDscore exhibited sensitivity to common chemotherapy drugs (such as cisplatin and docetaxel). To summarize, our study developed a novel PCDscore model that comprehensively analyzed different cell death modes, providing an accurate prediction of clinical prognosis and drug sensitivity for LIHC patients.

MiR-155 regulates M2 polarization of hepatitis B virus-infected tumour-associated macrophages which in turn regulates the malignant progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) initiated by hepatitis B virus (HBV) infection is a complicated process. MiR-155 can alter the immune microenvironment to affect the host's anti-infective ability. This study investigated the mechanism by which miR-155 affects tumour-associated macrophage (TAM) polarization at a molecular level, thus affecting the malignant progression of HBV+ HCC. MiR-155 and TAM-related cytokine expression were analysed by qRT-PCR. The distribution of TAMs was detected by immunohistochemistry. The effect of the aberrant miR-155 expression on macrophage polarization was examined by flow cytometry. The targeted relationship was verified by dual-luciferase assay, and the protein level of src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was detected by western blot. The proliferation of HCC cells was examined by CCK-8 and colony formation assays. Invasion and migration of HCC cells were detected by transwell assay. In HBV+ HCC tissues, miR-155 was significantly highly expressed and the number of CD206-positive TAM (CD206+ TAM) and CD68-positive TAM (CD68+ TAM) were higher than those in HBV- HCC tissues. In addition, miR-155 overexpression significantly promoted M2-type macrophage polarization, whilst miR-155 silencing expression significantly promoted M1-type macrophage polarization. Besides, the miR-155/SHIP1 axis accelerated HCC cell invasion, proliferation and migration by inducing M2-type macrophage polarization. MiR-155 accelerates HCC cell proliferation, migration and invasion by targeting SHIP1 expression and inducing macrophage M2 polarization. This finding provides new insights into the development of novel therapeutic strategies for combatting HBV+ HCC and a new reference for exploring anti-tumour immunotherapy.

UCK2 regulated by miR-139-3p regulates the progression of hepatocellular carcinoma cells.

Objective: This study mainly explores how UCK2 impacts the progression of hepatocellular carcinoma (HCC). Methods: Mature miRNA and mRNA expression data along with the clinical data of HCC were provided by The Cancer Genome Atlas to mine differentially expressed miRNAs and mRNAs. Expression levels of UCK2 and miR-139-3p in HCC were tested through quantitative real-time PCR. How UCK2 and miR-139-3p impacted HCC cell activities were detected by Transwell, wound healing and cell proliferation approaches. Whether miR-139-3p could bind to UCK2 was detected by dual-luciferase assay. Results: This investigation found evidently high levels of UCK2 in both HCC tissue and cells and its marked association with poor prognosis. Overexpression of UCK2 could significantly promote the behaviors of HCC cells. In addition, poorly expressed miR-139-3p was inversely associated with UCK2. Dual-luciferase method also proved the association. The rescue experiment showed that miR-139-3p regulated cell behaviors in HCC through targeting UCK2. Conclusion: Highly expressed UCK2 was mediated by miR-139-3p to modulate cell behaviors in HCC. It is assumed that UCK2 is a possible target of HCC for cancer therapy purposes.

Globally, a large number of patients succumb to hepatocellular carcinoma (HCC) each year. Only 10­37% patients can undergo surgery because of hepatic failure and advanced tumors. Though the recovery rate after excision is 20­30%, the 5-year survival rate is low, and postoperative recurrence rate is high. Despite the widespread application of HCC screening, only few patients in the early stage have been diagnosed. Hence, it is urgent to explore its potential mechanism. This study investigates the relationship between aberrant expression of mRNA and malignancy of HCC cells. Finally, the abnormally high expression of UCK2 is correlated with patients' low survival rate and poor prognosis.

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.