RESUMO
BACKGROUND: Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated. METHODS: In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values. RESULTS: In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 + T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context. CONCLUSIONS: These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.
Assuntos
Proteínas de Membrana , Neoplasias , Microambiente Tumoral , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Variações do Número de Cópias de DNA , Metilação de DNA , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Regulação Neoplásica da Expressão Gênica , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Instabilidade de Microssatélites , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/metabolismo , Prognóstico , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. METHODS: A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion. Western blot was carried out to detect the level of Bcl-2, AKT, and PI3K protein expression in different groups. RESULTS: The proliferation of HepG2 cells were significantly decreased after ICOS siRNA transfection (EG group). Similarly, the results of the Transwell experiment showed that invasion of HepG2 cells in the EG group was clearly reduced compared to the negative control (NC) and blank control groups (CON). Western blot analysis showed that knockdown of ICOS expression reduced the levels of Bcl-2 and AKT, and also significantly up-regulated the level of PI3K phosphorylation (P < 0.01). CONCLUSION: Down-regulating ICOS expression in HepG2 cells suppressed cell proliferation and invasion. The underlying mechanism may be related to the expression of the downstream factor, PI3K/AKT.
Assuntos
Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/fisiologia , Neoplasias Hepáticas/patologia , Western Blotting , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Colorimetria , Regulação para Baixo , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/sangue , Proteínas Proto-Oncogênicas c-akt/sangue , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Abstract Background This study determined the regulatory effects of inducible T-cell co-stimulators (ICOS) in human hepatocellular carcinoma HepG2 cells using a RNA interference (RNAi) technique. Methods A RNAi technique was used to knockdown the expression of ICOS. ICOS expression after knockdown was detected as mRNA and protein levels by RT-PCR and Western blot, respectively. A MTT colorimetric assay was used to detect cell proliferation, and the Transwell assay was used to detect cell invasion. Western blot was carried out to detect the level of Bcl-2, AKT, and PI3K protein expression in different groups. Results The proliferation of HepG2 cells were significantly decreased after ICOS siRNA transfection (EG group). Similarly, the results of the Transwell experiment showed that invasion of HepG2 cells in the EG group was clearly reduced compared to the negative control (NC) and blank control groups (CON). Western blot analysis showed that knockdown of ICOS expression reduced the levels of Bcl-2 and AKT, and also significantly up-regulated the level of PI3K phosphorylation (P < 0.01). Conclusion Down-regulating ICOS expression in HepG2 cells suppressed cell proliferation and invasion. The underlying mechanism may be related to the expression of the downstream factor, PI3K/AKT.
Assuntos
Humanos , Regulação Neoplásica da Expressão Gênica/genética , Carcinoma Hepatocelular/patologia , Proteína Coestimuladora de Linfócitos T Induzíveis/fisiologia , Neoplasias Hepáticas/patologia , Regulação para Baixo , Western Blotting , Colorimetria , Carcinoma Hepatocelular/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Fosfatidilinositol 3-Quinases/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Interferência de RNA , Proliferação de Células , Proteínas Proto-Oncogênicas c-akt/sangue , Técnicas de Silenciamento de Genes , Células Hep G2 , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Neoplasias Hepáticas/metabolismo , Invasividade NeoplásicaRESUMO
We collected 2768 Influenza-like illness emergency public health incidents from April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting System. After screening by strict inclusion and exclusion criteria, there were 613 outbreaks analyzed with susceptible-exposed-infectious/asymptomatic-removed model in order to estimate the proportion of asymptomatic individuals (p) and the effective reproduction number (Rt). The relation between Rt and viral subtypes, regions, outbreak sites, populations, and seasons were analyzed. The mean values of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up to 0.94. Different subtypes, provinces, regions, and sites of outbreak had statistically significantly different Rt. In particular, the southern region also manifested different Rt by affected population size and seasonality. Our results provide China and also the rest of the world a reference to understand characteristics of transmission and develop prevention and control strategies.