Prognostic Value and Immune Infiltration Analysis of Nuclear Factor Erythroid-2 Family Members in Ovarian Cancer

Ovarian cancer (OC) often presents at an advanced stage and is still one of the most frequent causes of gynecological cancer-related mortality worldwide. The nuclear factor erythroid-2 (NFE2) transcription factors include nuclear factor, erythroid 2 like 1 (NFE2L1), NFE2L2, and NFE2L3. NFE2 members bind to the antioxidant-response element (ARE) region and activate the expression of targeted genes. The distinct functions of NFE2 members in OC remain poorly elucidated. Several online bioinformatics databases were applied to determine gene expression, prognosis, mutations, and immune infiltration correlation in OC patients. NFE2L1 and NFE2L2 were decreased in OC, whereas NFE2L3 was increased. NFE2L2 and NFE2L3 were significantly correlated with the clinical stages of OC. High NFE2L1 level was significantly associated with short progression-free survival (PFS) in patients with OC ( HR = 1.18 , P = 0.021 ), while high NFE2L2 expression strongly correlated with long PFS ( HR = 0.77 , P = 0.00067 ). High NFE2L3 expression was associated with better overall survival and postprogression survival in OC. Functional analysis showed that NFE2 members mainly focused on transcription coactivator activities. Genetic alterations of NFE2 members were found in 13% of OC patients, and amplification ranked the top. The expression of NFE2 members was significantly correlated with immune infiltration of CD4+ T cells, CD8+ T cells, B cells, macrophages, and neutrophils in OC. Our study provides novel insights into the roles and prognostic potential of NFE2 family members in OC.

Bioinformatic Evaluation of the miRNAs Targeting ACE2 Gene in COVID-19

Introduction: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which began in late 2019 in Wuhan, China, has become a global epidemic. Angiotensin 2 converting enzyme (ACE2) acts as a receptor for host function to cause acute coronavirus 2 acute respiratory syndrome (SARS-CoV-2). ACE2 is abundantly expressed in different cells of different human organs. In human physiology, ACE2 is a major player in the renin-angiotensin-aldosterone (RAAS) system by degrading angiotensin II. Many factors have been associated with altered ACE2 expression and the severity and progression of COVID-19, including microRNAs that may be effective in it. Identifying pathological changes due to SARS-CoV-2 infection is important because it has major implications for understanding the pathophysiology of COVID-19 and developing evidence-based treatment strategies. Currently, many intervention strategies are being explored in ongoing clinical trials. Objective: The aim of this study is to use bioinformatics databases to find potential antiviral therapies against SARS-CoV-2 through host microRNAs (miRNAs) that can reduce viral gene expression to inhibit virus entry and replication. Methods: Using different algorithms in TargetScan, DIANA, ENCORI and miRWalk databases, the potential microRNAs were identified that target ACE2. Then, a score table was prepared from the candidate microRNAs, based on the affinity of the seed region of microRNAs and the 3`-UTR region of the ACE2 gene. Finally, microRNAs with higher scores were chosen as candidates for practical analysis. Results: The results of Bioinformatical analysis showed that Has-miR-200c-3p, Has-miR-29a, Has-miR-29c, and Has-miR-942 are most likely to inhibit ACE2. These microRNAs are the most potent factors that might be affected on ACE2 during virulence. Conclusion: It seems that ACE2 is under the control of the miR-200c-3p and plays a crucial role in the pathophysiology process. Therefore, this microRNA can be considered as a suitable new candidate for experimental evaluation.

Analysis of intronless genes involved in oscillation and differentiation

The genomes of higher eukaryotes are replete with intron-containing genes. Transcription of these genes produces precursor mRNAs containing intervening sequences, which are subsequently removed and the exons spliced together to form the mature mRNA. However, a small proportion of eukaryotic protein-coding genes are intronless and therefore bypass post-transcriptional splicing events. Although a large proportion of intronless genes are known to code for certain types of proteins, their specific role in the genome of higher organism is perplexing. This research set out to elucidate the functions of intronless genes in humans by studying their involvement in the expression pattern of oscillatory gene that occurs in the pre-somitic mesoderm of developing embryo. Twenty-seven (27) human homologs of mouse oscillatory genes were analysed to determine the number of exons present in them using various bioinformatics databases. The result obtained identified two intronless genes –NRARP and ID1 – which are associated with the Notch signalling pathway of the segmentation clock. This represented 7.4% of the total oscillatory genes analysed. No intronless gene was found in the Wnt and FGF signalling pathways – two other pathways famous for oscillatory gene expression. The proteins encoded by the intronless genes are involved in several important biological processes including angiogenesis, cell cycle control and in the regulation of cellular senescence. Although oscillatory genes had fewer numbers of introns compared to the non-oscillatory genes, the intronless genes were not implicated in the regulation of the precise timing events of the segmentation clock. This result may also point to the fact that the rapid expression rate of the oscillatory genes in the PSM may favour the reduced intron length of the oscillatory genes.

CCR5 and Biological Complexity: The Need for Data Integration and Educational Materials to Address Genetic/Biological Reductionism at the Interface of Ethical, Legal, and Social Implications

In the age of genomics, public understanding of complex scientific knowledge is critical. To combat reductionistic views, it is necessary to generate and organize educational material and data that keep pace with advances in genomics. The view that CCR5 is solely the receptor for HIV gave rise to demand to remove the gene in patients to create host HIV resistance, underestimating the broader roles and complex genetic inheritance of CCR5. A program aimed at providing research projects to undergraduates, known as CODE, has been expanded to build educational material for genes such as CCR5 in a rapid approach, exposing students and trainees to large bioinformatics databases and previous experiments for broader data to challenge commitment to biological reductionism. Our students organize expression databases, query environmental responses, assess genetic factors, generate protein models/dynamics, and profile evolutionary insights into a protein such as CCR5. The knowledgebase generated in the initiative opens the door for public educational information and tools (molecular videos, 3D printed models, and handouts), classroom materials, and strategy for future genetic ideas that can be distributed in formal, semiformal, and informal educational environments. This work highlights that many factors are missing from the reductionist view of CCR5, including the role of missense variants or expression of CCR5 with neurological phenotypes and the role of CCR5 and the delta32 variant in complex critical care patients with sepsis. When connected to genomic stories in the news, these tools offer critically needed Ethical, Legal, and Social Implication (ELSI) education to combat biological reductionism.

A Multilevel Systemic Pan-cancer Analysis: Collagen Triple Helix Repeat Containing-1 is a Potential Target for Tumor Immunotherapy

Background: Cancer is one of the leading causes of pathological death in humans. Although CTHRC1 is a prooncogene highly expressed in a variety of tumor tissues, the specific biological mechanisms of CTHRC1 involvement in cancer development need to be elucidated. Methods: In the present study, nine online bioinformatics databases were employed to explore the potential prognostic and grading value of CTHRC1 in generalized cancer as well as its potential role in regulating tumor immunity. Results: Data from GEPIA2.0, Oncomine, TNMplot, Kaplan-Meier Plotter and TISIDB database had consistently demonstrated that CTHRC1 was associated with the expression, prognosis and typing in most cancer tissues. Cbioportal and SMART analysis revealed that genomic changes and methylation of CTHRC1 in most tumor tissues. Finally, Sangerbox and TIMER database analysis suggested that CTHRC1 was involved in the changes of immune cell components in tumor immune microenvironment, with certain heterogeneity. Meanwhile, CTHRC1 was correlated with TMB, MSI, neoantigen and tumor immune checkpoint, especially CD276. Conclusion: CTHRC1 had the potential as a prognostic and grading molecular marker for pan-cancer. And CTHRC1-related targeting agents may be a novel breakthrough in tumor immunotherapy.

Construction of Novel mRNA-miRNA-lncRNA Regulatory Networks Associated with Prognosis of HCV Related HCC

Background: Infection with hepatitis C virus (HCV) can cause hepatic fibrosis and cirrhosis, thereby significantly increasing the risk of HCC development. Many prior studies have shown that oncogenesis and cancer progression are governed by competing endogenous RNA (ceRNA) networks composed of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs. As such, we herein sought to identify and evaluate the prognostic relevance of novel ceRNA network related to HCC associated with HCV. Methods: Differentially expressed genes (DEGs) in the GSE140845 Gene Expression Omnibus (GEO) dataset were identified using NetworkAnalyst, and were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Gene, Genome (KEGG) pathway, and Reactome analyses. In addition, a protein-protein interaction (PPI) network was generated, and key hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were additionally used to establish putative ceRNA networks for HCV-related HCC. Results: 372 and 360 upregulated and downregulated significant DEGs were identified, respectively. Functional enrichment analyses suggested that DE-mRNAs were associated with nuclear division, the cell cycle, and ATPase activity. The top 11 genes with the greatest degree of connectivity among these DE-mRNAs were selected for subsequent prognostic evaluation. The differential expression of six of these candidate mRNAs (BUB1, BUB1B, CDC20, CDC45, CDK1, NDC80) in liver tissue was validated. After further analyses of the expression and prognostic relevance of the miRNAs and lncRNAs predicted to lie upstream of these DE-mRNAs, we identified 22 miRNAs and 4 lncRNAs significantly associated with poorer-HCV-related HCC prognosis. By combining the results of these analyses, we also identified the BUB1-hsa-miR-193a-3p-MALAT1 ceRNA sub-network as being related to the survival of these patients. Conclusion: This study providing novel insights into the mRNA-miRNA-lncRNA ceRNA network and reveals potential lncRNA biomarkers in HCV related HCC.

A Comprehensive Analysis of Potential Gastric Cancer Prognostic Biomarker ITGBL1 Associated With Immune Infiltration and Epithelial–mesenchymal Transition

Background: Integrin, beta-like 1 (ITGBL1) is involved in a variety of human malignancies. However, the information on the involvement of ITGBL1 in gastric carcinoma (GC) is limited. Hence, this study aimed to further explore the functions and mechanisms of ITGBL1 in GC. Methods: First, multiple bioinformatics databases, including Oncomine, Timer, UALCAN, and Kaplan–Meier Plotter, were used to predict the expression level and prognostic value of ITGBL1, as well as its association with immune infiltration and epithelial–mesenchymal transition (EMT) in GC. Quantitative reverse transcription–polymerase chain reaction and immunohistochemical analysis were used to to detect the expression of ITGBL1 in both GC tissues and cells. Then, targeted silencing of ITGBL1 in GC cells was further to examine the biological functions of ITGBL1.Results: These databases revealed that ITGBL1 was overexpressed and affected the overall survival in GC. Besides, the expression of ITGBL1 positively correlated with immune-infiltrating cells and EMT-related markers. Subsequently, molecular biology experiments verified these predictions. In GC tissues and cells, ITGBL1 was notably overexpressed. Loss-of-function studies showed that the knockdown of ITGBL1 significantly suppressed migration and invasion but promoted apoptosis in MGC803 GC cells. Furthermore, the inhibition of ITGBL1 resulted in remarkably increased protein expression levels of cadherin 1 (CDH1), while the expression of Vimentin, Snail, and TGF-β1 was downregulated, indicating the initiation and progression of GC caused by ITGBL1 partly via inducing EMT. Conclusion: To sum up, the findings indicated that ITGBL1 acted as a valuable oncogenic factor in GC.

miR-433-3p Targets AJUBA to Inhibit Malignant Progression of Glioma

<b><i>Introduction:</i></b> Glioma is the most aggressive and malignant type of tumors among primary intracranial tumors. miR-433-3p has been verified to be correlated with the formation and progression of many types of cancers. <b><i>Methods:</i></b> In this study, the effects of miR-433-3p and AJUBA on the proliferation, migration, and invasion of glioma and the molecular mechanisms were investigated. We analyzed bioinformatics databases and conducted cell biology experiments to determine that compared with adjacent tissue and normal cells, the expression level of miR-433-3p in glioma tissue and cells was lower, while the expression level of AJUBA was higher. Overexpressing miR-433-3p could significantly inhibit the proliferation, migration, and invasion of glioma cells and promote cell apoptosis. <b><i>Results:</i></b> In addition, after overexpressing miR-433-3p and AJUBA, it was found that overexpressing AJUBA could attenuate the inhibitory effect of overexpressing miR-433-3p on the proliferation, migration, and invasion of glioma cells, which suggested that miR-433-3p regulated the biological function of glioma by downregulating AJUBA expression. <b><i>Conclusion:</i></b> These results proved that miR-433-3p could target to inhibit the expression of AJUBA, thus inhibiting the biological function and malignant progression of glioma.