Integrated single-cell and spatial transcriptomic analysis reveals YBX1 drives immune regulation in GBM progression.

The RNA modification 5-methylcytosine (m5C) is widespread across various RNA types, significantly impacting RNA stability and translational efficiency. Accumulating evidence highlights its significant role within the tumorigenesis and progression of multiple malignancies. Nevertheless, the specific process through m5C is implicated in Glioblastoma (GBM) remains unclear. We conducted acomprehensive analysis of m5C expression distribution in single-cell GBM data. Our findings revealed elevated m5C scores in GBM single-cell data compared to the normal group. Additionally, multiple tumors exhibited significantly higher m5C scores than the normal group. Moreover, there was a positive correlation observed between the m5C score and inflammation score. m5C regulatory factor YBX1 exhibited a heightened expression in GBM, correlating closely with metastatic tendencies and an unfavorable prognosis across various cancer types. YBX1 has different biological functions in myeloid cells 1 and myeloid cells 2. YBX1 may act as immunosuppressive regulator by inhibiting the NF-κB pathway and inflammatory response in myeloid cells 1. YBX1 is essential for immune infiltrates, which creates a highly immunosuppressive tumor microenvironment by TNF signaling pathway in myeloid cells 2. YBX1+ neoplastic cells promote cell proliferation by NF-κB pathway. APOE mediates the interaction of YBX1+ myeloid cells and neoplastic cells by NF-κB.

Lactoferrin may inhibit the development of cancer via its immunostimulatory and immunomodulatory activities (Review).

Lactoferrin (Lf) is secreted by ectodermal tissue and has a structure similar to that of transferrin. Although Lf seems to be multifunctional, its main function is related to the natural defense system of mammals. The present review aims to highlight the major actions of Lf, including the regulation of cell growth, the inhibition of toxic compound formation, the removal of harmful free radicals and its important role in immune response regulation. Moreover, Lf has antibacterial, antiviral, antioxidant, anticancer and anti­inflammatory activities. In addition, the use of Lf for functionalization of drug nanocarriers, with emphasis on tumor­targeted drug delivery, is illustrated. Such effects serve as an important theoretical basis for its future development and application. In neurodegenerative diseases and the brains of elderly people, Lf expression is markedly upregulated. Lf may exert an anti­inflammatory effect by inhibiting the formation of hydroxyl free radicals. Through its antioxidant properties, Lf can prevent DNA damage, thereby preventing tumor formation in the central nervous system. In addition, Lf specifically activates the p53 tumor suppressor gene.

Gut microbiota influence tumor development and Alter interactions with the human immune system.

Recent scientific advances have greatly enhanced our understanding of the complex link between the gut microbiome and cancer. Gut dysbiosis is an imbalance between commensal and pathogenic bacteria and the production of microbial antigens and metabolites. The immune system and the gut microbiome interact to maintain homeostasis of the gut, and alterations in the microbiome composition lead to immune dysregulation, promoting chronic inflammation and development of tumors. Gut microorganisms and their toxic metabolites may migrate to other parts of the body via the circulatory system, causing an imbalance in the physiological status of the host and secretion of various neuroactive molecules through the gut-brain axis, gut-hepatic axis, and gut-lung axis to affect inflammation and tumorigenesis in specific organs. Thus, gut microbiota can be used as a tumor marker and may provide new insights into the pathogenesis of malignant tumors.

Clinical relationships between the rs2212020 and rs189897 polymorphisms of the ITGA9 gene and epithelial ovarian cancer.

To better understand the role of integrin subunit alpha 9 (ITGA9) gene polymorphism in epithelial ovarian cancer (EOC), we investigated the distribution of ITGA9 gene polymorphisms (rs2212020 and rs189897) and revealed whether these polymorphisms were associated with a curative effect in EOC. It was found that rs2212020 and rs189897 were correlated significantly with EOC incidence. The frequency of the C allele of rs2212020 was significantly higher in EOC patients than in the control group (P = 0.009, χ2 = 6.857). The population with the C allele of rs2212020 had a higher EOC risk than the population with the T allele (hazard ratio = 1.97, 95.0% CI = 1.178-3.299). Further, our results showed that the CC genotype was a risk factor for EOC. Regarding the association between ITGA9 and the sensitivity to platinum-based chemotherapy in EOC, there were no statistically significant differences in the frequencies of the rs189897 and rs2212020 polymorphisms between the chemosensitive group and the control group. In multivariate analysis, the patients with the TT genotype of rs189897 had longer progression free survival (PFS) than the patients without this genotype (P = 0.010, OR = 2.491). The AT genotype of rs189897 was a risk factor for PFS in EOC. These findings suggested that rs189897 and rs2212020 could play important roles in EOC diagnosis and prognosis.

The identification of key genes in nasopharyngeal carcinoma by bioinformatics analysis of high-throughput data.

Nasopharyngeal carcinoma (NPC) is a common pattern of regional malignancy in the south of China, especially in Guangdong province. The development of computerized tomography (CT) technology and the improvement of radiotherapy scheme can improve the survival rate of NPC patients. However, the prevalence and recurrence rate of NPC are increasing every year. It is urgent for us to uncover the molecular mechanism of NPC. In this study, we used scientific information retrieval from the GEO (gene expression omnibus) database to download the GSE12452, which contained 41 samples, including 31 nasopharyngeal carcinoma samples and 10 control samples. With the help of GO (gene ontology) analysis, KEGG (kyoto encyclopedia of genes and genomes) analysis, PPI (protein-protein interaction) network model construction, and WGCNA (weighted gene co-expression network analysis), we found 6896 differentially expressed genes, which affected the biological processes included cell cycle process, DNA metabolic process, DNA repairing, immune response, cell activation, regulation of immune system process, inflammatory response. The 20 hub genes present in front of us are SYK, PIK3CG, FYN, ACACB, LRRK2, RIPK4, RAC2, PIK3CD, PTPRC, LCR, RAD51, MAD2L1, CDK1, PCNA, GMPS, CCNB1, GAPDH, CCNA2, RFC4, TOP2A. In the future, these are the areas where we need to focus on the molecular mechanism of NPC.

CD38 affects the biological behavior and energy metabolism of nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is the most common malignant tumor type in Southern China and South­East Asia. Cluster of differentiation (CD)38 is highly expressed in the human immune system and participates in the activation of T, natural killer and plasma cells mediated by CD2 and CD3 through synergistic action. CD38 is a type II transmembrane glycoprotein, which was observed to mediate diverse activities, including signal transduction, cell adhesion and cyclic ADP­ribose synthesis. However, the significance of CD38 in NPC biological behavior and cellular energy metabolism has not been examined. In order to elucidate the effect of CD38 on the biological behavior of NPC cells, stable CD38­overexpressed NPC cell lines were established. It was demonstrated that CD38 promoted NPC cell proliferation with Cell Counting Kit­8 and colony formation assays. It was also indicated that CD38 inhibited cell senescence, and promoted cell metastasis. Furthermore, it was determined that CD38 promoted the conversion of cells to the S phase and decreased the content of reactive oxygen species and Ca2+. Additionally, cell metabolism assays demonstrated that CD38 increased the concentration of ATP, lactic acid, cyclic adenosine monophosphate and human ADP/acrp30 concentration in NPC cells. To investigate the possible mechanism, bioinformatics analysis and mass spectrometry technology was used to determine the most notably changing molecule and signaling pathways, and it was determined and verified that CD38 regulated the metabolic­associated signaling pathways associated with tumor protein 53, hypoxia inducible factor­1α and sirtuin 1. The present results indicated that CD38 may serve a carcinogenic role in NPC by regulating metabolic­associated signaling pathways.

Identification of differentially expressed genes in cervical cancer by bioinformatics analysis.

Cervical cancer is the most common gynecological malignancy. In recent years, the incidence of cervical cancer has had a younger trend. Cervical cancer morbidity and mortality rates have been significantly reduced due to recent decades of cervical cytology screening leading to the early detection and treatment of cervical cancer and precancerous lesions. There are a number of methods used to treat cervical cancer and improve the survival rate. However, the prevalence and recurrence rates of cervical cancer are increasing every year. There is an urgent requirement for a better understanding of the molecular mechanism cervical cancer development. The present study used scientific information retrieval from the Gene Expression Omnibus database to download the GSE26511 dataset, which contained 39 samples, including 19 cervical cancer lymph node-positive samples and 20 cervical cancer lymph node-negative samples. Using Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and weighted gene co-expression network analysis, 1,263 differentially expressed genes were found that affected the biological processes, including 'cell cycle process', 'signaling pathways', 'immune response', 'cell activation', 'regulation of immune system process' and 'inflammatory response'. These areas should be the focus of study for cervical cancer in the future.

The receptor for activated protein kinase C promotes cell growth, invasion and migration in cervical cancer.

Cervical cancer is one of the most common malignant tumors in women all over the world. However, the exact etiology of cervical cancer remains unclear. The receptor for activated protein kinase C (RACK1) is reported to be involved in tumorigenesis and tumor progression. Besides, the prognostic value of RACK1 in several kinds of tumors has been identified. However, there are limited studies on the functional role of RACK1 in cervical cancer. In this study, we tested the expression level of RACK1 by immunohistochemistry and western blot technologies and find that it is upregulated in cervical cancer. Colony formation and CCK8 assays indicate that RACK1 promotes cell proliferation in CaSki cervical cancer cells. While the silence of RACK1 decreases the cell proliferation in CCK8 analysis. ß-galactosidase staining suggests that RACK1 decreases cell senescence in cervical cancer cells. Invasion and migration assay show that RACK1 promotes the invasion and migration of cervical cancer cells. Also, when RACK1 was silenced, it exerts the opposite result. Furthermore, the mRNA expression levels of MMP­3, MMP­9 and MMP­10 were upregulated in RACK1­overexpressed CaSki cells by qPCR analysis. RACK1 also induces S phase accumulation in cell cycle analysis and suppresses cell apoptosis in cervical cancer cells. Flow cytometry analysis of mitochondria functions suggests that RACK1 increases the mitochondrial membrane potential (Δψm) levels to prevent mitochondrial apoptosis in cervical cancer cells. To explore the possible mechanism of RACK1, we tested and found that RACK1 upregulates the expression of NF-κB, cyclin D1 and CDK4 and downregulates the expression of p53, p38, p21 and STAT1 in cervical cancer cells. These results suggest that RACK1 promotes cell growth and invasion and inhibits the senescence and apoptosis in cervical cancer cells probably by affecting the p53 pathway.