Types Of Human Cancer Research Articles

Reduced intestinal-to-diffuse conversion and immunosuppressive responses underlie superiority of neoadjuvant immunochemotherapy in gastric adenocarcinoma.

Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment-naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25%vs. 4%, p<0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal-to-diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8+ T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor-kappa B (NF-κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal-to-diffuse conversion and reprogramming to an immuno-active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy.

Anticancer effect of the oncolytic Newcastle disease virus harboring the PTEN gene on glioblastoma.

Glioblastoma (GBM) is one of the most lethal types of human brain cancer and is characterized by rapid growth, an aggressive nature and a poor prognosis. GBM is highly heterogeneous, and often involves several genetic mutations and abnormalities. Genetic disorders or low expression of phosphatase and tensin homolog (PTEN) are associated with GBM occurrence, progression and poor prognosis of patients with GBM. However, effective delivery of PTEN for expression in GBM cells within the brain remains challenging. The aim of the present study was to develop a therapeutic strategy to restore PTEN expression in GBM cells by utilizing a recombinant Newcastle disease virus (rNDV) vector expressing the human PTEN gene (rNDV-PTEN). Methods included infection of U87-MG cells with rNDV-PTEN, followed by assessments of PTEN expression, and cell proliferation, migration and apoptosis. Additionally, an orthotopic GBM mouse model was used to evaluate the in vivo efficacy of rNDV-PTEN. Infection with recombinant rNDV-PTEN treatment increased PTEN protein expression in the cytoplasm of the U87-MG cells, reduced cell proliferation and migration, and induced apoptosis by inhibiting the AKT/mTOR signaling pathway. In the orthotopic GBM mouse model, rNDV-PTEN significantly reduced tumor size and improved survival rates. Magnetic resonance imaging and in vivo imaging analyses confirmed the targeted delivery and efficacy of rNDV-PTEN. These findings highlight the usefulness of rNDV-PTEN as a promising therapeutic agent for GBM, representing a potential advancement in treatment, especially for patients with PTEN deficiency.

A Pan-Cancer Analysis of GAPDH as a Common Biomarker for Various Cancers

Background: The present study aimed to investigate the expression level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and explore its prognostic value across 24 different human cancers. This investigation was conducted using comprehensive bioinformatics and in vitro approaches that involved multiple layers of analysis. Methods: GAPDH expression and methylation levels were assessed via bioinformatics tools and validated using cell lines through RNA sequencing and targeted bisulfite sequencing analyses. The potential prognostic significance of GAPDH was evaluated through the use of a Kaplan–Meier plotter. Additionally, cBioPortal was employed to investigate genetic alterations associated with this gene. Pathway analysis was conducted using DAVID. Furthermore, a correlation analysis between GAPDH expression and CD8+ T immune cells was performed using TIMER and CDT. Lastly, a gene-drug interaction network analysis was conducted using Cytoscape to examine the relationship between GAPDH and drugs. Results: The GAPDH was found commonly up-regulated in 24 types of human cancers and its up-regulation was significantly correlated with the poor relapse-free survival (RFS) and overall survival (OS) of BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. This implies that GAPDH plays a significant role in the development of these cancers. The GAPDH up-regulation was also noticed to be associated with the different clinicopathological features of BLCA, CESC, HNSC, KIRP, LIHC, and LUAD patients. Pathway analysis has shown GAPDH involvement in different diverse pathways. Furthermore, notable correlations were observed between the expression of GAPDH and its promoter methylation level, genetic alterations, as well as the level of CD8+ T immune cells. Moreover, we identified significant regulatory drugs targeting GAPDH that have the potential to modulate its expression and potentially prevent conditions such as BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. Conclusion: Based on our findings, GAPDH emerged as a promising diagnostic and prognostic biomarker for BLCA, CESC, HNSC, KIRP, LIHC, and LUAD.

STARD7 could be an immunological and prognostic biomarker: from pan-cancer analysis to hepatocellular carcinoma validation

BackgroundAs the emergence of technologies such as sequencing and gene mapping, significant advancements have been made in understanding the landscape of tumors. However, the effective treatment of tumors continues to pose a tremendous challenge in clinical practice, which highlights the importance of predicting tumor markers and studying drug resistance mechanisms. The prognosis and differential expression of STARD7 in human pan-cancer were investigated by bioinformatic methods and experimental verification.MethodsThe expression, diagnostic, and prognostic significance of the STARD7 gene were comprehensive analyzed using bioinformatics techniques. Furthermore, we validated our projected outcomes in liver cancer through experimental methodologies, including the use of qRT-PCR, CCK8 and transwell assays.ResultsThe STARD7 gene exhibits differential expression in 25 tumors, with high expression observed in 22 tumors. These distinct expression patterns within different tumor types are closely associated with poor prognosis and diagnosis. Furthermore, the STARD7 gene plays a role in regulating the tumor immune microenvironment. Methylation levels of STARD7 vary among 20 types of tumors and are correlated with survival outcomes. Furthermore, the experiment results demonstrated that STARD7 is highly expressed in hepatocellular carcinoma cells. Suppression of STARD7 significantly impedes the proliferation, migration, and invasion of HepG-2 and SMMC-7721 cells.ConclusionsSTARD7 has the potential to function as a crucial prognostic biomarker and exhibit correlation with tumor immunity in various types of human cancers. The implications of our findings extend to informing cancer immune-therapy and promoting the advancement of precision immune-oncology.

IRF2 loss is associated with reduced MHC I pathway transcripts in subsets of most human cancers and causes resistance to checkpoint immunotherapy in human and mouse melanomas

BackgroundIn order for cancers to progress, they must evade elimination by CD8 T cells or other immune mechanisms. CD8 T cells recognize and kill tumor cells that display immunogenic tumor peptides bound to MHC I molecules. One of the ways that cancers can escape such killing is by reducing expression of MHC I molecules, and loss of MHC I is frequently observed in tumors. There are multiple different mechanisms that can underly the loss of MHC I complexes on tumor and it is currently unclear whether there are particular mechanisms that occur frequently and, if so, in what types of cancers. Also of importance to know is whether the loss of MHC I is reversible and how such loss and/or its restoration would impact responses to immunotherapy. Here, we investigate these issues for loss of IRF1 and IRF2, which are transcription factors that drive expression of MHC I pathway genes and some killing mechanisms.MethodsBioinformatics analyses of IRF2 and IRF2-dependent gene transcripts were performed for all human cancers in the TCGA RNAseq database. IRF2 protein-DNA-binding was analyzed in ChIPseq databases. CRISRPcas9 was used to knock out IRF1 and IRF2 genes in human and mouse melanoma cells and the resulting phenotypes were analyzed in vitro and in vivo.ResultsTranscriptomic analysis revealed that IRF2 expression was reduced in a substantial subset of cases in almost all types of human cancers. When this occurred there was a corresponding reduction in the expression of IRF2-regulated genes that were needed for CD8 T cell recognition. To test cause and effect for these IRF2 correlations and the consequences of IRF2 loss, we gene-edited IRF2 in a patient-derived melanoma and a mouse melanoma. The IRF2 gene-edited melanomas had reduced expression of transcripts for genes in the MHC I pathway and decreased levels of MHC I complexes on the cell surface. Levels of Caspase 7, an IRF2 target gene involved in CD8 T cell killing of tumors, were also reduced. This loss of IRF2 caused both human and mouse melanomas to become resistant to immunotherapy with a checkpoint inhibitor. Importantly, these effects were reversible. Stimulation of the IRF2-deficient melanomas with interferon induced the expression of a functionally homologous transcription factor, IRF1, which then restored the MHC I pathway and responsiveness to CPI.ConclusionsOur study shows that a subset of cases within most types of cancers downregulates IRF2 and that this can allow cancers to escape immune control. This can cause resistance to checkpoint blockade immunotherapy and is reversible with currently available biologics.

EBV infection alters DNA methylation in primary human colon cells: A path to inflammation and carcinogenesis?

Epstein-Barr Virus (EBV) is associated with several types of human cancers, and changes in DNA methylation are reported to contribute to viral-driven carcinogenesis, particularly in cancers of epithelial origin. In a previous study, we demonstrated that EBV infects human primary colonic cells (HCoEpC) and replicates within these cells, leading to pro-inflammatory and pro-tumorigenic effects. Notably, these effects were mostly prevented by inhibiting viral replication with PAA. Interestingly, the EBV-induced effects correlated with the upregulation of DNMT1 and were counteracted by pretreating cells with 5-AZA, suggesting a role for DNA hypermethylation.Building on this background, the current study investigates the methylation changes induced by EBV infection in HCoEpC, both in the presence and absence of PAA, or ERK1/2 and STAT3 inhibitors, pathways known to be activated by EBV and involved in the dysregulation of methylation in tumor cells. The genome-wide methylation analysis conducted in this study allowed us to identify several biological processes and genes affected by these epigenetic changes, providing insights into the possible underlying mechanisms leading to the pathological effects induced by EBV. Specifically, we found that the virus induced significant methylation changes, with hypermethylation being more prevalent than hypomethylation. Several genes involved in embryogenesis, carcinogenesis, and inflammation were affected.

The activation of the Notch signaling pathway by UBE2C promotes the proliferation and metastasis of hepatocellular carcinoma

UBE2C, a ubiquitin-conjugating enzyme, functions as an oncogene in different types of human cancers. Nonetheless, the exact influence of UBE2C on the development of HCC via regulation of ubiquitination remains uncertain. Here, we found that UBE2C displayed elevated levels of expression in HCC and was associated with an unfavorable prognosis, as evidenced by the analysis of the TCGA database and the examination of clinical specimens. The role of UBE2C in HCC revealed its ability to promote the growth and metastasis of HCC. Mechanistically, UBE2C activated Notch signaling, as evidenced by the upregulation of N1ICD and Hes1, crucial components of the Notch pathway, and activation of the RBP-JK luciferase reporter by UBE2C. Finally, rescue experiments demonstrated that the oncogenic role of UBE2C was eliminated through treatment with the Notch inhibitor DAPT, while overexpression of N1ICD alleviated the anticarcinogenic impact of knockdown of UBE2C. Altogether, the results of our study indicate that UBE2C plays a role in the activation of Notch signaling and could potentially serve as a viable target for therapeutic interventions in HCC.

Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma.

Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

Busulfan Chemotherapy Downregulates TAF7/TNF-α Signaling in Male Germ Cell Dysfunction.

Background: Busulfan is an FDA-approved alkylating drug used in the chemotherapy of advanced acute myeloid leukemia. The precise mechanisms by which Busulfan kills spermatogonia stem cells (SSCs) are not yet completely understood. Methods: Using a murine model, we evaluated Busulfan-induced apoptosis and DNA damage signaling between testis and ovary tissues. We executed RT-qPCR, analyzed single-nuclei RNA sequencing data and performed in situ hybridization for the localization of the gene expression in the tissues. Results: The results indicate that, in contrast to female germ cells, haploid male germ cells undergo significant apoptosis following Busulfan chemotherapy. Moreover, a gene enrichment analysis revealed that reactive oxygen species may activate the inflammatory response in part through the TNF-α/NF-κB signaling pathway. Interestingly, in the testis, the mRNA levels of TNF-α and TAF7 (TATA box-binding protein-associated factor 7) are downregulated, and testosterone levels suppressed. Mechanistically, the promoter of TNF-α has a conserved motif for binding TAF7, which is necessary for its transcriptional activation and may require further in-depth study. We next analyzed the tumorigenic function of TAF7 and revealed that it is highly overexpressed in several types of human cancers, particularly testicular germ cell tumors, and associated with poor patient survival. Therefore, we executed in situ hybridization and single-nuclei RNA sequencing, finding that less TAF7 mRNA is present in SSCs after chemotherapy. Conclusions: Thus, our data indicate a possible function of TAF7 in the regulation of SSCs and spermatogenesis following downregulation by Busulfan. These findings may account for the therapeutic effects of Busulfan and underlie its potential impact on cancer chemotherapy prognosis.

Identification of Key Immune and Cell Cycle Modules and Prognostic Genes for Glioma Patients through Transcriptome Analysis.

Gliomas, the most prevalent type of primary brain tumor, stand out as one of the most aggressive and lethal types of human cancer. To uncover potential prognostic markers, we employed the weighted correlation network analysis (WGCNA) on the Chinese Glioma Genome Atlas (CGGA) 693 dataset to reveal four modules significantly associated with glioma clinical traits, primarily involved in immune function, cell cycle regulation, and ribosome biogenesis. Using the least absolute shrinkage and selection operator (LASSO) regression algorithm, we identified 11 key genes and developed a prognostic risk score model, which exhibits precise prognostic prediction in the CGGA 325 dataset. More importantly, we also validated the model in 12 glioma patients with overall survival (OS) ranging from 4 to 132 months using mRNA sequencing and immunohistochemical analysis. The analysis of immune infiltration revealed that patients with high-risk scores exhibit a heightened immune infiltration, particularly immune suppression cells, along with increased expression of immune checkpoints. Furthermore, we explored potentially effective drugs targeting 11 key genes for gliomas using the library of integrated network-based cellular signatures (LINCS) L1000 database, identifying that in vitro, both torin-1 and clofarabine exhibit promising anti-glioma activity and inhibitory effect on the cell cycle, a significant pathway enriched in the identified glioma modules. In conclusion, our study provides valuable insights into molecular mechanisms and identifying potential therapeutic targets for gliomas.

The antioxidant and selective apoptotic activities of modified auraptene-loaded graphene quantum dot nanoparticles (M-AGQD-NP)

BackgroundPancreatic and Gastric cancers are very aggressive and deadly types of cancer that require effective treatment strategies to stop their progression. Nano-drug delivery systems, like those using Auraptene-loaded GQD nanoparticles, play a crucial role in addressing this need by delivering targeted and controlled treatments to cancer cells, making treatment more effective, and reducing side effects. The study focused on investigating the effects of Auraptene, an efficient anticancer compound when loaded into Graphene Quantum Dots (GQDs) on types of human cancer cells.MethodsTo create auraptene-loaded graphene quantum dot nanoparticles (AGQD-NP) (Unmodified and modified types) a combination of hydrothermal and high-energy homogenization methods was used. The nanoparticles were characterized by conducting DLS (Dynamic light scattering), FTIR (Fourier-transform infrared spectroscopy), FESEM (Field Emission Scanning Electron microscopy), and zeta potential analysis. bioactivity of AGQD-NP was assessed through tests, including antioxidant capacity measured by ABTS and DPPH scavenging abilities well as cytotoxicity tested using MTT assay on both human cancer cell lines and normal human vascular endothelial cells.ResultsThe modified AGQD-NP (M-AGQD-NP) demonstrated antioxidant properties by neutralizing free radicals. They also displayed selective toxicity, towards human gastric adenocarcinoma cell-line (AGS) and human pancreatic adenocarcinoma (PANC) cancer cells with IC50 values recorded at 78.8 µg/mL and 89.72 µg/mL respectively. The specific targeting of gastric cancer cells was evident from the differing IC50 values compared to the Human breast adenocarcinoma cell line (MCF-7), Human hepatocellular carcinoma cell line (Hella), and normal vascular endothelial cells (Huvec). Additionally, the induced apoptotic death, in the human pancreatic adenocarcinoma (PANC) cancer cells was confirmed through AO/PI staining and Annexin-based flow cytometry revealing increased expression levels of P53, Caspase3, BAX, and Caspase8.ConclusionIn summary, the M-AGQD-NP have shown encouraging effects displaying antioxidant capabilities and a specific focus, on pancreatic and gastric cancer cells. These findings indicate uses for AGQD-NP as an efficient apoptosis inducer in cancer treatment. Additional In-vivo researches are required to validate their effectiveness, in living organisms.

A Pan-Cancer Analysis of GAPDH as a Common Biomarker for Various Cancers

Objective: To investigate the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and explore its prognostic value across 24 different human cancers. This investigation was conducted using comprehensive bioinformatics and in vitro approaches, incorporating multiple layers of analysis. Methods: GAPDH expression and methylation levels were assessed using bioinformatics tools and validated in cell lines through RNA-seq and targeted bisulfite-seq analyses. The potential prognostic significance of GAPDH was evaluated using the KM plotter. Additionally, cBioPortal was employed to investigate genetic alterations associated with this gene. Pathway analysis was conducted using DAVID. Furthermore, a correlation analysis between GAPDH expression and CD8+ T immune cells was performed using TIMER and CDT. Finally, a gene-drug interaction network analysis was conducted using Cytoscape to examine the relationship between GAPDH and various drugs. Results: GAPDH was found to be commonly upregulated in 24 types of human cancers, with its upregulation significantly correlated with poor relapse-free survival (RFS) and overall survival (OS) in BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. This suggests that GAPDH plays a significant role in the development of these cancers. GAPDH upregulation was also associated with various clinicopathological features in patients with BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. Pathway analysis revealed GAPDH’s involvement in diverse pathways. Additionally, notable correlations were observed between GAPDH expression and its promoter methylation level, genetic alterations, and CD8+ T immune cell levels. Moreover, several regulatory drugs targeting GAPDH were identified, with the potential to modulate its expression and potentially prevent conditions such as BLCA, CESC, HNSC, KIRP, LIHC, and LUAD. Conclusion: Based on our findings, GAPDH emerges as a promising diagnostic and prognostic biomarker for BLCA, CESC, HNSC, KIRP, LIHC, and LUAD.

Association of MORC2 expression with progression-free survival in cervical cancer patients treated with concurrent chemoradiotherapy.

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein, and has been proposed as a prognostic biomarker associated with survival in some types of human cancer, but the role of MORC2 in cervical cancer remains unknown. Here, we investigated the role of MORC2 expression in predicting the survival outcomes of locally advanced cervical cancer patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT). In this retrospectively study, we detected MORC2 immunohistochemical expression on 55 biopsies from patients who underwent CCRT. The association between the MORC2 expression and various clinicopathological characteristics were analyzed, as were association between MORC2 expression and locoregional failure and progression-free survival (PFS) of cervical cancer patients. MORC2 expression was positively associated with pelvic node metastasis and locoregional failure. Higher MORC2 expression was a significant indicator of worse PFS. Our results suggest that MORC2 expression may be a prognostic indicator in patients with locally advanced cervical cancer undergoing CCRT.

IRF2 loss is associated with reduced MHC I pathway transcripts in subsets of most human cancers and causes resistance to checkpoint immunotherapy in human and mouse melanomas.

In order for cancers to progress, they must evade elimination by CD8 T cells or other immune mechanisms. CD8 T cells recognize and kill tumor cells that display immunogenic tumor peptides bound to MHC I molecules. One of the ways that cancers can escape such killing is by reducing expression of MHC I molecules, and loss of MHC I is frequently observed in tumors. There are multiple different mechanisms that can underly the loss of MHC I complexes on tumor and it is currently unclear whether there are particular mechanisms that occur frequently and, if so, in what types of cancers. Also of importance to know is whether the loss of MHC I is reversible and how such loss and/or its restoration would impact responses to immunotherapy. Here, we investigate these issues for loss of IRF1 and IRF2, which are transcription factors that drive expression of MHC I pathway genes and some killing mechanisms. Bioinformatics analyses of IRF2 and IRF2-dependent gene transcripts were performed for all human cancers in the TCGA RNAseq database. IRF2 protein-DNA-binding was analyzed in ChIPseq databases. CRISRPcas9 was used to knock out IRF1 and IRF2 genes in human and mouse melanoma cells and the resulting phenotypes were analyzed in vitro and in vivo. Transcriptomic analysis revealed that IRF2 expression was reduced in a substantial subset of cases in almost all types of human cancers. When this occurred there was a corresponding reduction in the expression of IRF2-regulated genes that were needed for CD8 T cell recognition. To test cause and effect for these IRF2 correlations and the consequences of IRF2 loss, we gene-edited IRF2 in a patient-derived melanoma and a mouse melanoma. The IRF2 gene-edited melanomas had reduced expression of transcripts for genes in the MHC I pathway and decreased levels of MHC I complexes on the cell surface. Levels of Caspase 7, an IRF2 target gene involved in CD8 T cell killing of tumors, were also reduced. This loss of IRF2 caused both human and mouse melanomas to become resistant to immunotherapy with a checkpoint inhibitor. Importantly, these effects were reversible. Stimulation of the IRF2-deficient melanomas with interferon induced the expression of a functionally homologous transcription factor, IRF1, which then restored the MHC I pathway and responsiveness to CPI. Our study shows that a subset of cases within most types of cancers downregulates IRF2 and that this can allow cancers to escape immune control. This can cause resistance to checkpoint blockade immunotherapy and is reversible with currently available biologics.

Prognostic biomarkers based on GUF1, EFTUD2 and GSPT1 targets affecting migration of gastric cancer cells.

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a protein coding gene which is involved in tumor development and progression in several types of human cancer, but little is known about the function of eEF1A2 proteins in gastric cancer (GC). This study aimed to investigate the effects of GUF1, EFTUD2 and GSPT1 on the migration of GC cells. The Oncomine and The Cancer Genome Atlas (TCGA) databases were used to evaluate the expression of GUF1, EFTUD2, GSPT1 and GSPT2 in GC and the association of eEF1A2 family with individual clinical characteristics. Kaplan-Meier (K-M) Plotter hinted the prognostic value of GUF1, EFTUD2, GSPT1 and GSPT2. GSE62254 and GSE66222 datasets were used to validate the expression of GUF1, EFTUD2, GSPT1. AGS cell line and GES line were also used for validating the function of GUF1, EFTUD2, GSPT1. RNA interference (RNAi) of GUF1, EFTUD2 and GSPT1 had been used to query those genes expression pattern and dissect the proliferation and migration in GC cell lines. GUF1, EFTUD2 and GSPT1 were significantly up-regulated in GC cell lines. High expression of GUF1, EFTUD2 and GSPT1 was correlated with cell proliferation and migration induced in GC cells. GUF1, EFTUD2 and GSPT1 may be potential novel oncogenes that helps to maintain the survival of GC cells. This study identified that high levels of GUF1, EFTUD2 and GSPT1 expression are predictive biomarkers for a poor prognosis in GC.

ERVcancer: A web resource designed for querying activation of human endogenous retroviruses across major cancer types

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, co-opted into the dynamic regulatory network of cellular potency in early embryonic development. In recent studies, resurgent HERVs' transcriptional activity has been frequently observed in many types of human cancers, suggesting their potential functions in the occurrence and progression of malignancy. However, a dedicated web resource for querying the relationship between activation of HERVs and cancer development is lacking. Here, we have constructed a database to explore the sequence information, expression profiles, survival prognosis, and genetic interactions of HERVs in diverse cancer types. Our database currently contains RNA sequencing data of 580 HERVs across 16,246 samples, including that of 6478 tumoral and 634 normal tissues, 932 cancer cell lines, as well as 151 early embryonic and 8051 human adult tissues. The primary goal is to provide an easily accessible and user-friendly database for professionals in the fields of bioinformatics, pathology, pharmacology, and related areas, enabling them to efficiently screen the activity of HERVs of interest in normal and cancerous tissues and evaluate the clinical relevance. The ERVcancer database is available at http://kyuanlab.com/ervcancer/.

A C->T Variation in 3'-Untranslated Region Elevates MED12 Protein Level in Breast Cancer That Relates to Better Prognosis.

Objective: Mediator complex subunit 12 (MED12) is among the most frequently mutated genes in various types of human cancers. However, there is still a lack of understanding regarding the role of MED12 in breast cancer patient. Therefore, the aim of this study is to explore the roles of MED12 in breast cancer. Materials and Methods: We utilized the UALCAN platform (http://ualcan.path.uab.edu/) for analyzing the transcriptional expression, protein expression, and protein phosphorylation data of MED12. Our study involved 35 breast cancer patients. From these samples, we extracted proteins and RNA. To obtain the sequence of MED12 3'-UTR, we performed reverse transcription-polymerase chain reaction and sequencing. We then used TargetScan to predict the miRNA targets of MED12 3'-UTR and confirmed the interactions between miRNAs and MED12 3'-UTR through dual luciferase assay. Results: The protein level of MED12 was upregulated in breast cancer, while the mRNA level did not show significant changes. Interestingly, higher levels of MED12 mRNA were associated with better prognosis, whereas patients with increased MED12 protein levels tended to have a poorer prognosis. Furthermore, through our analysis of the MED12 3'-UTR sequence, we identified a specific C->T variation that was unique to breast tumors. We also identified four miRNAs (miR-204, -211, -450 b, and -518a) that directly target MED12 3'-UTR. Most important, this C->T variation disrupts the interaction between MED12 3'-UTR and miR-450b, ultimately leading to the upregulation of MED12 in breast cancer. Conclusion: Our study revealed a significant finding regarding a mutation site in the MED12 3'-UTR that contributes to the upregulation of MED12 in breast cancer. This mutation disrupts the interactions between specific miRNAs and MED12 mRNA, leading to increased expression of MED12. These findings have important implications for breast cancer diagnosis, as this mutation site can serve as a potent biomarker.

Hepatocyte growth factor promotes melanoma metastasis through ubiquitin-specific peptidase 22-mediated integrins upregulation

Hepatocyte growth factor (HGF) plays a critical role in promoting tumor migration, invasion, and metastasis, partly by upregulating integrins. The molecular mechanisms behind how HGF facilitates integrin-mediated tumorigenesis are not fully understood. In this study, we demonstrate that the ubiquitin-specific peptidase 22 (USP22) is essential for HGF-induced melanoma metastasis. HGF treatment dramatically increased the expression of both USP22 and multiple integrin family members in particular ITGAV, ITGB3, and ITGA1. An unbiased analysis of the TCGA database reveals integrins as common downstream targets of both USP22 and HGF across multiple human cancer types. Notably, CRISPR-mediated deletion of USP22 completely eliminates HGF-induced integrin expression in melanoma cells. At the molecular level, USP22 acts as a bona fide deubiquitinase for Sp1, a transcription factor for the ITGAV, ITGB3, and ITGA1 genes. USP22 interacts with and inhibits Sp1 ubiquitination, protecting against Sp1 proteasomal degradation. Supporting this, immunohistology analysis detects a positive correlation among USP22, Sp1, and integrin αv in human melanoma tissues. This study identifies the death from the signature gene USP22 as a critical positive regulator for HGF-induced integrin expression by deubiquitinating the Sp1 transcription factor during melanoma metastasis.

Prevalence and Impact of Emerging Chemical Contaminants in the Life Style Products on Human Health

In recent times, the increasing prevalence of harmful pollutants in our environment, originating from chemicals of various lifestyle products, has emerged as significant challenge for mankind. The purpose of this article was to explore the past literature concerning the consequences of various emerging contaminants in the everyday lifestyle products on human health. The chemical compounds, derived from various human activities, have become an integral part of our global ecosystem and are essential for the functioning of modern society. Chemical compounds are discharged into the environment from different origins, including rural, urban, and industrial areas. These compounds can come from everyday products such as cosmetics, personal care items, household cleaners, and pharmaceuticals. Additionally, consumer products like soaps, shampoos, conditioners, lotions, and perfumes are used on a daily basis worldwide. These products contain a variety of chemicals that can contribute to environmental pollution. Various substances such as paraben, triclosan, phthalate, fragrances, antimicrobial agents, UV filters, and heavy metals are commonly found in these products. Scientists have determined that these ingredients can have detrimental effects on both humans and other organisms. The impacts of these chemical contaminants vary from changes in reproductive health and various types of cancer in humans. Additionally, aquatic organisms are also impacted by these substances. The significance of this matter is heightened by the rising global demand for beauty products, which commonly utilize a diverse array of chemical compounds in their production.

Phytocompounds and Nanoformulations for Anticancer Therapy: A Review.

Cancer is a complex disease that affects millions of people and remains a major public health problem worldwide. Conventional cancer treatments, including surgery, chemotherapy, immunotherapy, and radiotherapy, have limited achievements and multiple drawbacks, among which are healthy tissue damage and multidrug-resistant phenotype onset. Increasing evidence shows that many plants' natural products, as well as their bioactive compounds, have promising anticancer activity and exhibit minimal toxicity compared to conventional anticancer drugs. However, their widespread use in cancer therapy is severely restricted by limitations in terms of their water solubility, absorption, lack of stability, bioavailability, and selective targeting. The use of nanoformulations for plants' natural product transportation and delivery could be helpful in overcoming these limitations, thus enhancing their therapeutic efficacy and providing the basis for improved anticancer treatment strategies. The present review is aimed at providing an update on some phytocompounds (curcumin, resveratrol, quercetin, and cannabinoids, among others) and their main nanoformulations showing antitumor activities, both in vitro and in vivo, against such different human cancer types as breast and colorectal cancer, lymphomas, malignant melanoma, glioblastoma multiforme, and osteosarcoma. The intracellular pathways underlying phytocompound anticancer activity and the main advantages of nanoformulation employment are also examined. Finally, this review critically analyzes the research gaps and limitations causing the limited success of phytocompounds' and nanoformulations' clinical translation.