Background: Liver cancer is one of the most common malignant tumors in the world. T cell-mediated antitumor immune response is the basis of liver cancer immunotherapy. Objective: To screen and analyze the RNAs associated with activated memory CD4 T cells and CD8 T cells in liver cancer. Methods: ESTIMATE was used to calculate the stromal and immune scores of tumor samples, which were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) in high and low stromal and immune scores were screened, followed by functional enrichment of overlapped DEGs. We then conducted a survival analysis to identify immune-related prognostic indicators and constructed protein-protein interaction (PPI) networks and ceRNA networks. Finally, chemical small-molecule–target interaction pairs associated with liver cancer were screened. Results: A total of 55,955 stromal-related DEGs and 1811 immune-related DEGs were obtained. The 1238 overlapped DEGs were enriched in 1457 biological process terms and 74 KEGG pathways. In addition, a total of 120 activated memory CD4 T cell-related genes and 309 CD8 T cell-related genes were identified. The survival analysis revealed that upregulated expression of T cell-related genes including EOMES, CST7, and CD5L indicated the favorable prognosis of liver cancer. EOMES was regulated by has-miR-23b-3p and has-miR-23b-3p was regulated by lncRNA AC104820.2 in the ceRNA network of activated memory CD4 T cell-related genes. In addition, EOMES was regulated by has-miR-23a-3p and has-miR-23a-3p was regulated by lncRNA AC000476.1 in the ceRNA network of CD8 T cells. Conclusion: T cell-related RNAs EOMES, CST7, CD5L, has-miR-23b-3p, and has-miR-23a-3p may be associated with the prognosis of liver cancer. And the molecular characteristics of these T cell-related genes were plotted.
Manganese (Mn) is a crucial trace element that actively participates in a diverse array of physiological processes. Mn is maintained at appropriate levels in the body by absorption and excretion by the body. Dysregulation of Mn homeostasis can lead to a variety of diseases, especially the accumulation of Mn in the brain, resulting in toxic side effects. We reviewed the metabolism and distribution of Mn at multiple levels, including organ, cellular and sub-cell levels. Mitochondria are the main sites of Mn metabolism and energy conversion in cells. Enhanced Mn superoxide dismutase activity reduces mitochondrial oxidative stress and inhibits cancer development. In addition, Mn enhances anti-cancer immune responses through the cGAS–STING pathway. We introduced various delivery vectors for Mn delivery to cancer sites for Mn supplementation and anti-cancer immunity. This review aims to provide new research perspectives for the application of Mn in the prevention and treatment of human diseases, especially by enhancing anti-cancer immune responses to inhibit cancer progression.
Increasing evidence suggested that cholesterol is an important integrant of cell membranes, that plays a key role in tumor progression, immune dysregulation, and pathological changes in epigenetic mechanisms. Based on these theories, there is a growing interest on targeting cholesterol in the treatment of cancer. Here, we comprehensively reviewed the major function of cholesterol on oncogenicity, the therapeutic targets of cholesterol and its metabolites in cancer, and provide detailed insight into the essential roles of cholesterol in mediating immune and epigenetic mechanisms of the tumor microenvironment. It is also worth mentioning that the gut microbiome is an indispensable component of cancer mediation because of its role in cholesterol metabolism. Finally, we summarized recent studies on the potential targets of cholesterol and their metabolism, to provide more therapeutic interventions in oncology.
Colorectal cancer (CRC) is one of the most considerably common malignancies of the alimentary system, with high mortality and incidence rates. The present study suggested that the occurrence of CR...
Background: Gut microbiota dysbiosis involved in the pathogenesis of colorectal cancer (CRC). The characteristics of enterotypes in CRC development have not been determined. Objective: To characterize the gut microbiota of healthy, adenoma, and CRC subjects based on enterotype. Methods: The 16 S rRNA sequencing data from 315 newly sequenced individuals and three previously published datasets were collected, providing total data for 367 healthy, 320 adenomas, and 415 CRC subjects. Enterotypes were analyzed for all samples, and differences in microbiota composition across subjects with different disease states in each enterotype were determined. The predictive values of a random forest classifier based on enterotype in distinguishing healthy, adenoma, and CRC subjects were evaluated and validated. Results: Subjects were classified into one of three enterotypes, namely, Bacteroide- (BA_E), Blautia- (BL_E), and Streptococcus- (S_E) dominated clusters. The taxonomic profiles of these three enterotypes differed among the healthy, adenoma, and CRC cohorts. BA_E group was enriched with Bacteroides and Blautia; BL_E group was enriched by Blautia and Coprococcus; S_E was enriched by Streptococcus and Ruminococcus. Relative abundances of these genera varying among the three human cohorts. In training and validation sets, the S_E cluster showed better performance in distinguishing among CRC patients, adenoma patients, and healthy controls, as well as between CRC and non-CRC individuals, than the other two clusters. Conclusion: This study provides the first evidence to indicate that changes in the microbial composition of enterotypes are associated with disease status, thereby highlighting the diagnostic potential of enterotypes in the treatment of adenoma and CRC.