Circular RNAs as a potential source of neoepitopes in cancer

Neoepitopes have attracted much attention as targets for immunotherapy against cancer. Therefore, efficient neoepitope screening technology is an essential step in the development of personalized vaccines. Circular RNAs (circRNAs) are generated by back-splicing and have a single-stranded continuous circular structure. So far, various circRNAs have been poorly characterized, though new evidence suggests that a few translated circRNAs may play a role in cancer. In the present study, circRNA was used as a source of neoepitope, a novel strategy as circRNA-derived neoepitopes have never been previously explored. The present study reports CIRC_neo (circRNA-derived neoepitope prediction pipeline), which is a comprehensive and automated bioinformatic pipeline for the prediction of circRNA-derived neoepitopes from RNA sequencing data. The computational prediction from sequencing data requires complex computational workflows to identify circRNAs, derive the resulting peptides, infer the types of human leukocyte antigens (HLA I and HLA II) in patients, and predict the neoepitopes binding to these antigens. The present study proposes a novel source of neoepitopes. The study focused on cancer-specific circRNAs, which have greatly expanded the source pool for neoepitope discovery. The statistical analysis of different features of circRNA-derived neoepitopes revealed that circRNAs could produce long proteins or truncated proteins. Because the peptides were completely foreign to the human body, they could be highly immunogenic. Importantly, circRNA-derived neoepitopes capable of binding to HLA were discovered. In the current study, circRNAs were systematically analyzed, revealing potential targets and novel research clues for cancer diagnosis, treatment, and prospective personalized vaccine research

Human papillomavirus and cervical cancer in the microbial world: exploring the vaginal microecology

The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing

Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index

IntroductionLung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index.MethodsRNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein–protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs.ResultsOverall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index.ConclusionOur study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance

Effect of Combined Treatment with Phenylalanine and 1-Methylcyclopropene on Anthocyanin Biosynthesis in Peach Peel

In order to explore the effect of postharvest treatment with combined phenylalanine (Phe) and 1-methylcyclopropene (1-MCP) on the appearance quality of peach fruits, bagged peach fruits were treated after harvest with water (control), Phe, 1-MCP or Phe combined with 1-MCP (Phe + 1-MCP). The changes in peach fruit phenotype, peel color difference, anthocyanin content, and the expression of genes associated with anthocyanidin and ethylene metabolism were measured during storage. The results showed that the single treatments with Phe or 1-MCP led to a higher peel anthocyanin content compared with the control group. Furthermore, the combined treatment was more effective in increasing the synthesis of anthocyanin than the single treatments. On the 6th day of storage, the anthocyanin content in the peel in the combined treatment group was 76.71 mg/kg, which was 7.29, 3.36, and 1.33 times higher than that in the control, Phe and 1-MCP groups, respectively. Phe + 1-MCP treatment effectively enhanced the expression of genes related to the synthesis of anthocyanins (PAL, CHS, CHI, F3H, DFR, ANS, UFGT, MYB10.1, bHLH-3 and WD40-1) and reduced the expression of genes related to ethylene synthesis and signal transduction (ACS, EIN4 and EIL) in peach peel. This study not only further confirmed that 1-MCP treatment can effectively promote the synthesis of anthocyanin in peach peel, but also found a synergistic effect between Phe and 1-MCP, which will provide a theoretical basis for the application of Phe + 1-MCP in the regulation of peach color after harvest

MicroRNA 1283 alleviates cardiomyocyte damage caused by hypoxia /reoxygenation via targeting GADD45A and inactivating the JNK and p38 MAPK signaling pathways

Background: Clarifying themolecular mechanism and identifying markers of myocardial ischemia/reperfusion injury is crucial for the treatment of acute myocardial infarction. Aims: This study aimed to investigate the roles and underlying regulatory mechanisms of microRNA 1283 (miR-1283) and GADD45A in cardiomyocytes injured by hypoxia /reoxygenation (H/R). Methods: Bioinformatic analyses were used to determine the expression of GADD45A and miR-1283 based on various datasets from the Gene Expression Omnibus database. Human embryonic cardiomyocytes were subjected to H/R to construct in vitro models. Real -time quantitative polymerase chain reaction and Western blot were used to detect mRNA and protein expression levels, respectively. The binding sites between miR-1283 and GADD45A were predicted by the TargetScan software and verified using dual luciferase reporter assays. Cell viability and apoptosis were detected with the use of Cell Counting Kit 8 and flow cytometry assays. Results: GADD45A and miR-1283 were upregulated or downregulated in myocardial infarction, respectively. MicroRNA 1283 expression was decreased in cardiomyocytes after H/R treatment. H/R treatment reduced cardiomyocyte viability and enhanced apoptosis, and these effects were abated by transfection of a miR1283 mimic and strengthened by transfection of a miR-1283 inhibitor. MicroRNA 1283 bound to the 3’ untranslated region of GADD45A and decreased the levels of GADD45A, which inhibited proliferation and promoted apoptosis in H/R -induced cardiomyocyte injury. Reintroduction of GADD45A attenuated the effect of miR-1283 on the viability and apoptosis of cardiomyocytes in H/R models. The JNK and p38 MAPK signaling pathways were regulated by the miR-283–GADD45A axis. Conclusions: The miR-1283–GADD45A axis may protect against H/R -induced cardiomyocyte injury by suppressing the JNK and p38 MAPK pathways

Mediating Effect of Organizational Learning Capacity on the Relationship between Relational Embeddedness and Innovation Performance in Freight Logistics Service

Cooperative innovation has become a critical method for freight logistics firms in supply chain management. The previous study has proved that relational embeddedness (RE) has a positive effect on service innovation performance. However, the influence of organizational learning capacity (OLC) has been widely ignored. This study focuses on explaining the mechanism of OLC on the relationship between RE and innovation performance of freight logistics service (IPFLS). Firstly, a theoretical model is constructed based on Social Network Theory, and four research hypotheses are presented. Secondly, a sample of 236 respondents from freight logistics firms in China is analyzed to test the hypotheses. Finally, several management implications and recommendations are suggested. The research results demonstrate that both RE and OLC have positive effects on IPFLS. Meanwhile, OLC partially mediates the relationship between RE and IPFLS. The findings provide practical guidance for managers to strengthen the relationship with partners and enhance OLC

Table_1_Circular RNAs as a potential source of neoepitopes in cancer.xlsx

Neoepitopes have attracted much attention as targets for immunotherapy against cancer. Therefore, efficient neoepitope screening technology is an essential step in the development of personalized vaccines. Circular RNAs (circRNAs) are generated by back-splicing and have a single-stranded continuous circular structure. So far, various circRNAs have been poorly characterized, though new evidence suggests that a few translated circRNAs may play a role in cancer. In the present study, circRNA was used as a source of neoepitope, a novel strategy as circRNA-derived neoepitopes have never been previously explored. The present study reports CIRC_neo (circRNA-derived neoepitope prediction pipeline), which is a comprehensive and automated bioinformatic pipeline for the prediction of circRNA-derived neoepitopes from RNA sequencing data. The computational prediction from sequencing data requires complex computational workflows to identify circRNAs, derive the resulting peptides, infer the types of human leukocyte antigens (HLA I and HLA II) in patients, and predict the neoepitopes binding to these antigens. The present study proposes a novel source of neoepitopes. The study focused on cancer-specific circRNAs, which have greatly expanded the source pool for neoepitope discovery. The statistical analysis of different features of circRNA-derived neoepitopes revealed that circRNAs could produce long proteins or truncated proteins. Because the peptides were completely foreign to the human body, they could be highly immunogenic. Importantly, circRNA-derived neoepitopes capable of binding to HLA were discovered. In the current study, circRNAs were systematically analyzed, revealing potential targets and novel research clues for cancer diagnosis, treatment, and prospective personalized vaccine research.</p

Table_4_Circular RNAs as a potential source of neoepitopes in cancer.xlsx

Neoepitopes have attracted much attention as targets for immunotherapy against cancer. Therefore, efficient neoepitope screening technology is an essential step in the development of personalized vaccines. Circular RNAs (circRNAs) are generated by back-splicing and have a single-stranded continuous circular structure. So far, various circRNAs have been poorly characterized, though new evidence suggests that a few translated circRNAs may play a role in cancer. In the present study, circRNA was used as a source of neoepitope, a novel strategy as circRNA-derived neoepitopes have never been previously explored. The present study reports CIRC_neo (circRNA-derived neoepitope prediction pipeline), which is a comprehensive and automated bioinformatic pipeline for the prediction of circRNA-derived neoepitopes from RNA sequencing data. The computational prediction from sequencing data requires complex computational workflows to identify circRNAs, derive the resulting peptides, infer the types of human leukocyte antigens (HLA I and HLA II) in patients, and predict the neoepitopes binding to these antigens. The present study proposes a novel source of neoepitopes. The study focused on cancer-specific circRNAs, which have greatly expanded the source pool for neoepitope discovery. The statistical analysis of different features of circRNA-derived neoepitopes revealed that circRNAs could produce long proteins or truncated proteins. Because the peptides were completely foreign to the human body, they could be highly immunogenic. Importantly, circRNA-derived neoepitopes capable of binding to HLA were discovered. In the current study, circRNAs were systematically analyzed, revealing potential targets and novel research clues for cancer diagnosis, treatment, and prospective personalized vaccine research.</p