Bioinformatics Analysis Methods Research Articles

Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target.

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

Genome-Wide Identification and Characterization of RdHSP Genes Related to High Temperature in Rhododendron delavayi.

Heat shock proteins (HSPs) are molecular chaperones that play essential roles in plant development and in response to various environmental stresses. Understanding R. delavayi HSP genes is of great importance since R. delavayi is severely affected by heat stress. In the present study, a total of 76 RdHSP genes were identified in the R. delavayi genome, which were divided into five subfamilies based on molecular weight and domain composition. Analyses of the chromosome distribution, gene structure, and conserved motif of the RdHSP family genes were conducted using bioinformatics analysis methods. Gene duplication analysis showed that 15 and 8 RdHSP genes were obtained and retained from the WGD/segmental duplication and tandem duplication, respectively. Cis-element analysis revealed the importance of RdHSP genes in plant adaptations to the environment. Moreover, the expression patterns of RdHSP family genes were investigated in R. delavayi treated with high temperature based on our RNA-seq data, which were further verified by qRT-PCR. Further analysis revealed that nine candidate genes, including six RdHSP20 subfamily genes (RdHSP20.4, RdHSP20.8, RdHSP20.6, RdHSP20.3, RdHSP20.10, and RdHSP20.15) and three RdHSP70 subfamily genes (RdHSP70.15, RdHSP70.21, and RdHSP70.16), might be involved in enhancing the heat stress tolerance. The subcellular localization of two candidate RdHSP genes (RdHSP20.8 and RdHSP20.6) showed that two candidate RdHSPs were expressed and function in the chloroplast and nucleus, respectively. These results provide a basis for the functional characterization of HSP genes and investigations on the molecular mechanisms of heat stress response in R. delavayi.

TEX19 increases the levels of CDK4 and promotes breast cancer by disrupting SKP2-mediated CDK4 ubiquitination

BackgroundGlobally, breast cancer in women is the fifth leading cause of cancer death. There is an urgent need to explore the molecular mechanism of breast cancer proliferation and metastasis.MethodTCGA database analysis was used to analyze genes expression in breast cancer and normal samples and the association between gene expression and prognosis. Immunohistochemical staining, qPCR and western blotting was sued to detected gene expression. The cell function tests were conducted to investigate the effects of TEX19 and CDK4 with abnormal expression on cell proliferation, migration, apoptosis, cell cycle, and colony formation. Bioinformatics analysis methods combined with CHX tracking experiment and Co-IP experiment were performed to screen and verify the downstream molecule and regulatory mechanism of TEX19. Besides, subcutaneous tumorigenesis model in nude mice was constructed.ResultsTEX19 was significantly upregulated in breast cancer, and the TEX19 level was related to tumor invasion and prognosis. TEX19 knockdown inhibited the proliferation and migration of breast cancer cells, increased cell apoptosis, and blocked the cell cycle in the G2 phase. Besides, TEX19 suppressed the growth of tumors in the body. Mechanically, TEX19 upregulated the level of CDK4 protein, which depended on the E3 ubiquitin ligase SKP2. Specifically, TEX19 knockdown and SKP2 protein overexpression destroyed the stability of CDK4 protein and enhanced the ubiquitination of CDK4 protein. Additionally, CDK4 knockdown inhibited the proliferation, migration, and colony formation of breast cancer cells, and alleviated the promotion of TEX19 overexpression on the proliferation and migration of breast cancer cell.ConclusionTEX19 and CDK4 were upregulated in breast cancer, and TEX19 increased the level of CDK4 protein by influencing SKP2-mediated ubiquitination of CDK4, thereby promoting the progression of breast cancer.

Novel candidate genes for environmental stresses response in Synechocystis sp. PCC 6803 revealed by machine learning algorithms.

Cyanobacteria have developed acclimation strategies to adapt to harsh environments, making them a model organism. Understanding the molecular mechanisms of tolerance to abiotic stresses can help elucidate how cells change their gene expression patterns in response to stress. Recent advances in sequencing techniques and bioinformatics analysis methods have led to the discovery of many genes involved in stress response in organisms. The Synechocystis sp. PCC 6803 is a suitable microorganism for studying transcriptome response under environmental stress. Therefore, for the first time, we employed two effective feature selection techniques namely and support vector machine recursive feature elimination (SVM-RFE) and LASSO (Least Absolute Shrinkage Selector Operator) to pinpoint the crucial genes responsive to environmental stresses in Synechocystis sp. PCC 6803. We applied these algorithms of machine learning to analyze the transcriptomic data of Synechocystis sp. PCC 6803 under distinct conditions, encompassing light, salt and iron stress conditions. Seven candidate genes namely sll1862, slr0650, sll0760, slr0091, ssl3044, slr1285, and slr1687 were selected by both LASSO and SVM-RFE algorithms. RNA-seq analysis was performed to validate the efficiency of our feature selection approach in selecting the most important genes. The RNA-seq analysis revealed significantly high expression for five genes namely sll1862, slr1687, ssl3044, slr1285, and slr0650 under ion stress condition. Among these five genes, ssl3044 and slr0650 could be introduced as new potential candidate genes for further confirmatory genetic studies, to determine their roles in their response to abiotic stresses.

A novel lncRNA associated with the prognosis of patients with colorectal cancer resists apoptosis through the LYN/BCL-2 pathway

PurposeWe found a novel lncRNA named lncAC138150.2 related to the overall survival and staging of patients with colorectal cancer (CRC) by bioinformatic analysis using data from the Cancer Genome Atlas (TCGA), and the study aimed to elucidate the function of lncAC138150.2 and underlying mechanisms. MethodsTarget molecules were knocked down by transfection with antisense oligonucleotides (ASOs), siRNAs, or lentiviruses and overexpressed by transfection with plasmids. The function of lncAC138150.2 was determined using histological, cytological, and molecular biology methods. The underlying mechanism of lncAC138150.2 function was investigated using RNA-seq, bioinformatics analysis, and molecular biology methods. ResultsThe expression of lncAC138150.2 was increased in colorectal tissues compared with paired normal tissues. The lncAC138150.2 knockdown increased apoptosis but did not change the cell proliferation, cell cycle distribution, or cell migration ability of CRC cells, while lncAC138150.2 overexpression decreased CRC apoptosis. lncAC138150.2 was mainly located in the cell nucleus, and each lncAC138150.2 transcript knockdown increased CRC apoptosis. BCL-2 pathway was significantly altered in apoptosis induced by lncAC138150.2 knockdown, which was alleviated by BAX knockdown. The expression of LYN was significantly decreased with lncAC138150.2 knockdown, LYN knockdown increased CRC apoptosis, and its overexpression completely alleviated CRC apoptosis induced by lncAC138150.2 knockdown. ConclusionlncAC138150.2 significantly inhibited CRC apoptosis and affected the prognosis of patients with CRC, through the LYN/BCL-2 pathway.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion’s analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Auxiliary diagnosis and prognosis evaluation of KIF4A, RAD51AP1 and CDKN3 in esophageal cancer

To investigate the expression of mRNA in esophageal cancer (ESCA) tissues and its potential and diagnostic and prognostic value by high-throughput sequencing data. Using the Cancer Genome Atlas Program (TCGA) database in USA by integrative bioinformatics analysis methods, the gene expression profiles and clinical data of 173 patients with ECSA were collected. The mRNA expression levels in ESCA tissue and para-cancerous tissue samples were analyzed using DESeq2, edgeR and limma to screen the differentially expressed genes (DEGs). DEGs-related protein network diagrams were drawn. GO and KEGG function enrichment analysis were performed and the hub genes were screened and the survival analysis of hub genes was analyzed. Genes related to the prognosis of ESCA were selected and their prognostic value in ESCA was analyzed. Finally, the receiver operating characteristic curve was drawn to evaluate its diagnostic value. The results showed that using TCGA cancer data, a total of 620 up-regulated DEGs and 668 down-regulated DEGs with significant differential expression between ESCA and para-cancerous tissues were screened. DEGs were mainly involved in receptor complexes, ubiquitin ligase complexes, etc., playing GTPase activity, phospholipid binding, and other molecular functions, and participating in the regulation of intracellular substance transport, small molecule metabolism, and other biological processes. Protein functional enrichment analysis showed that these proteins were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, Epstein-Barr virus infection, neutrophil extracellular trap formation, and other pathways involved in the formation and development process of ESCA. Survival analysis showed that the overall survival rate of ESCA patients with high expression of KIF4A, RAD51AP1, and CDKN3 was significantly shortened, and the difference was statistically significant (P<0.05). Furthermore, the areas under the curve (AUC) of KIF4A, RAD51AP1, and CDKN3 for diagnosing esophageal cancer were 0.956, 0.951 and 0.979, respectively, with sensitivities and specificities both exceeding 80%. Additionally, ROC results of the combined diagnostic model of these three genes showed an AUC of 0.979, with sensitivities and specificities of 0.914 and 1, respectively. This indicates that KIF4A, RAD51AP1 and CDKN3 have individual or combined auxiliary diagnostic value for ESCA. In conclusion, KIF4A, RAD51AP1 and CDKN3 have high diagnostic efficiency for ESCA, and their increased expression is closely related to the prognosis, suggesting that these three genes could be used as auxiliary diagnostic and prognostic factors for ESCA.

Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis.

Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases. In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells. Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases. This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.

Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.

S100A9 exacerbates sepsis-induced acute lung injury via the IL17-NFκB-caspase-3 signaling pathway

BackgroundSepsis-induced acute lung injury (ALI) is associated with considerable morbidity and mortality in critically ill patients. S100A9, a key endothelial injury factor, is markedly upregulated in sepsis-induced ALI; however, its specific mechanism of action has not been fully elucidated. MethodsThe Gene Expression Omnibus database transcriptome data for sepsis-induced ALI were used to screen for key differentially expressed genes (DEGs). Using bioinformatics analysis methods such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses, the pathogenesis of sepsis-induced ALI was revealed. Intratracheal infusion of lipopolysaccharide (LPS, 10 mg/kg) induced ALI in wild-type (WT) and S100A9 knockout mice. Multiomics analyses (transcriptomics and proteomics) were performed to investigate the potential mechanisms by which S100A9 exacerbates acute lung damage. Hematoxylin-eosin, Giemsa, and TUNEL staining were used to evaluate lung injury and cell apoptosis. LPS (10 μg/mL)-induced murine lung epithelial MLE-12 cells were utilized to mimic ALI and were modulated by S100A9 lentiviral transfection. The impact of S100A9 on cell apoptosis and inflammatory responses were identified using flow cytometry and PCR. The expression of interleukin (IL)-17–nuclear factor kappa B (NFκB)–caspase-3 signaling components was identified using western blotting. ResultsSix common DEGs (S100A9, S100A8, IFITM6, SAA3, CD177, and MMP9) were identified in the six datasets related to ALI in sepsis. Compared to WT sepsis mice, S100A9 knockout significantly alleviated LPS-induced ALI in mice, with reduced lung structural damage and inflammatory exudation, decreased exfoliated cell and protein content in the lung lavage fluid, and reduced apoptosis and necrosis of pulmonary epithelial cells. Transcriptomic analysis revealed that knocking out S100A9 significantly affected 123 DEGs, which were enriched in immune responses, defense responses against bacteria or lipopolysaccharides, cytokine-cytokine receptor interactions, and the IL-17 signaling pathway. Proteomic analysis revealed that S100A9 knockout alleviated muscle contraction dysfunction and structural remodeling in sepsis-induced ALI. Multiomics analysis revealed that S100A9 may be closely related to interferon-induced proteins with tetratricopeptide repeats and oligoadenylate synthase-like proteins. LPS decreased MLE12 cell activity, accompanied by high expression of S100A9. The expression of IL-17RA, pNFκB, and cleaved-caspase-3 were increased by S100A9 overexpression and reduced by S100A9 knockdown in LPS-stimulated MLE12 cells. S100A9 knockdown decreases transcription of apoptosis-related markers Bax, Bcl and caspase-3, alleviating LPS-induced apoptosis. ConclusionsS100A9 as a key biomarker of sepsis-induced acute lung injury, and exacerbates lung damage and epithelial cell apoptosis induced by LPS via the IL-17–NFκB–caspase-3 signaling pathway.

Iron metabolism disorder and multiple sclerosis: a comprehensive analysis.

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS. The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS. This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)). This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.

The mechanism of action and experimental verification of Gan-song Yin on renal clear cell carcinoma based on network pharmacology and bioinformatics

BackgroundGan-song Yin (GSY) is originated from the scripture “Gan-song Pills”, a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless.MethodsFirstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis.ResultsWith the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR, JUN, MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein.ConclusionsNetwork pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies.

Single-Nucleus Sequencing of Silkworm Larval Brain Reveals the Key Role of Lysozyme in the Antiviral Immune Response in Brain Hemocytes

Introduction: The brain is considered as an immune-privileged organ, yet innate immune reactions can occur in the central nervous system of vertebrates and invertebrates. Silkworm (Bombyx mori) is an economically important insect and a lepidopteran model species. The diversity of cell types in the silkworm brain, and how these cell subsets produce an immune response to virus infection, remains largely unknown. Methods: Single-nucleus RNA sequencing (snRNA-seq), bioinformatics analysis, RNAi, and other methods were mainly used to analyze the cell types and gene functions of the silkworm brain. Results: We used snRNA-seq to identify 19 distinct clusters representing Kenyon cell, glial cell, olfactory projection neuron, optic lobes neuron, hemocyte-like cell, and muscle cell types in the B. mori nucleopolyhedrovirus (BmNPV)-infected and BmNPV-uninfected silkworm larvae brain at the late stage of infection. Further, we found that the cell subset that exerts an antiviral function in the silkworm larvae brain corresponds to hemocytes. Specifically, antimicrobial peptides were significantly induced by BmNPV infection in the hemocytes, especially lysozyme, exerting antiviral effects. Conclusion: Our single-cell dataset reveals the diversity of silkworm larvae brain cells, and the transcriptome analysis provides insights into the immune response following virus infection at the single-cell level.

Single-cell RNA sequencing reveals the transcriptional heterogeneity of Tbx18-positive cardiac cells during heart development.

The T-box family transcription factor 18 (Tbx18) has been found to play a critical role in regulating the development of the mammalian heart during the primary stages of embryonic development while the cellular heterogeneity and landscape of Tbx18-positive (Tbx18+) cardiac cells remain incompletely characterized. Here, we analyzed prior published single-cell RNA sequencing (scRNA-seq) mouse heart data to explore the heterogeneity of Tbx18+ cardiac cell subpopulations and provide a comprehensive transcriptional landscape of Tbx18+ cardiac cells during their development. Bioinformatic analysis methods were utilized to identify the heterogeneity between cell groups. Based on the gene expression characteristics, Tbx18+ cardiac cells can be classified into a minimum of two distinct cell populations, namely fibroblast-like cells and cardiomyocytes. In terms of temporal heterogeneity, these cells exhibit three developmental stages, namely the MEM stage, ML_P0 stage, and P stage Tbx18+ cardiac cells. Furthermore, Tbx18+ cardiac cells encompass several cell types, including cardiac progenitor-like cells, cardiomyocytes, and epicardial/stromal cells, as determined by specific transcriptional regulatory networks. The scRNA-seq results revealed the involvement of extracellular matrix (ECM) signals and epicardial epithelial-to-mesenchymal transition (EMT) in the development of Tbx18+ cardiac cells. The utilization of a lineage-tracing model served to validate the crucial function of Tbx18 in the differentiation of cardiac cells. Consequently, these findings offer a comprehensive depiction of the cellular heterogeneity within Tbx18+ cardiac cells.

Pan-cancer analysis of SERPINE family genes as biomarkers of cancer prognosis and response to therapy.

Background: Serine protease inhibitor E (SERPINE) family genes participate in the tumor growth, cancer cell survival and metastasis. However, the SERPINE family members role in the prognosis and their clinical therapeutic potentials in various human cancer types have not been elaborately explored. Methods: We preliminarily analyzed expression levels and prognostic values of SERPINE family genes, and investigated the correlation between SERPINEs expression and tumor microenvironment (TME), Stemness score, clinical characteristic, immune infiltration, tumor mutational burden (TMB), immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of SERPINEs from DAVID and KOBAS databases. Results: SERPINE1, SERPINE2, and SERPINE3 expression were upregulated in nine cancers, twelve cancers, and six cancers, respectively. The expression of SERPINE family genes was associated with the prognosis in several cancers from The Cancer Genome Atlas (TCGA). Furthermore, SERPINE family genes expression also had a significant relation to stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. SERPINE1 and SERPINE2 expression significantly increased in tumor advanced stage in colon adenocarcinoma (COAD). Results showed that SERPINE1 and SERPINE2 expression were negatively related with B cells and Monocytes, respectively. SERPINE2 expression had a significantly positive relation with B cells and Macrophages. In terms of TMB, SERPINE1, SERPINE2, and SERPINE3 were found to associated with TMB in seven cancers, fourteen cancers, and four cancers, respectively. Moreover, all SERPINE gene family members were significantly correlated with immune subtypes. SERPINE1 expression had a significantly positive or negative correlation with drug sensitivity. Conclusion: The study indicated the great potential of SERPINE family genes as biomarkers for prognosis and provided valuable strategies for further investigation of SERPINE family genes as potential targets in cancer.

Identification of Mitophagy-Related Genes in Sepsis

Background: Numerous studies have shown that mitochondrial damage induces inflammation and activates inflammatory cells, leading to sepsis, while sepsis, a systemic inflammatory response syndrome, also exacerbates mitochondrial damage and hyperactivation. Mitochondrial autophagy eliminates aged, abnormal or damaged mitochondria to reduce intracellular mitochondrial stress and the release of mitochondria-associated molecules, thereby reducing the inflammatory response and cellular damage caused by sepsis. In addition, mitochondrial autophagy may also influence the onset and progression of sepsis, but the exact mechanisms are unclear. background: Sepsis is a critical systemic infection, a syndrome of severe inflammatory response of the organism to various pathogenic microorganisms. Methods: In this study, we mined the available publicly available microarray data in the GEO database (Home - GEO - NCBI (nih.gov)) with the aim of identifying key genes associated with mitochondrial autophagy in sepsis. objective: In this study, we used a bioinformatics approach to integrate multiple microarray data to screen for mitochondrial autophagy-related hub genes associated with sepsis onset and progression in a more scientific and systematic manner. Results: We identified four mitophagy-related genes in sepsis, TOMM20, TOMM22, TOMM40, and MFN1. method: Robust rank aggregation (RRA) Conclusion: This study provides preliminary evidence for the treatment of sepsis and may provide a solid foundation for subsequent biological studies. result: we constructed a PPI network combined with RRA analysis method to finally identify 4 key genes, namely TOMM20, TOMM22, TOMM40, and MFN1. conclusion: In this study, we used a bioinformatics analysis method, RRA, to integrate five gene microarray datasets to identify pivotal genes associated with mitochondrial autophagy in sepsis. Gene ontology (GO) functional annotation results show that these hub genes are mainly enriched in mitochondrial transport and establishment of protein localization to mitochondrion. Finally, we constructed the PPI network with the top 100 genes obtained from the rra method analysis. Based on the RRA results, the PPI results and the mitochondrial autophagy-related genes we found in the Reactome Pathway Database, we finally identified four key genes as TOMM20, TOMM22, TOMM40, and MFN1, respectively.

Systematic Analysis to Identify the MIR99AHG-has-miR-21-5p-EHD1 CeRNA Regulatory Network as Potential Biomarkers in Lung Cancer.

Lung cancer (LC) remains an extremely lethal disease worldwide, and effective prognostic biomarkers are at top priority. With the rapid development of high-throughput sequencing and bioinformatic analysis methods, the quest to characterize cancer transcriptomes continues to move forward. However, the integrated systematic analysis of lncRNA-miRNA-mRNA regulatory network in LC is lacking. In this study, we collected samples of cancer tissues and adjacent normal tissues from patients with lung cancer and conducted transcriptome and small RNA sequencing to identify differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs). The regulatory roles of miRNAs in LC were explained by functional analysis on DEM-targeted genes. The lncRNA-miRNA pairs, miRNA-mRNA pairs, and lncRNA-mRNA pairs were identified and combined to construct the interplay of lncRNA-miRNA-mRNA. We evaluated the prognostic value of selected lncRNA-miRNA-mRNA by Kaplan-Meier analysis. Finally, we analyzed the expression levels of selected DEM, DELs, and DEGs in lung cancer patients and healthy people to verify our findings. A total of 1492 DEGs, 12 DEMs, and 604 DELs were identified in LC patients. Based on the bioinformatic analysis and the regulatory mechanism of ceRNAs, 3 lncRNAs (GATA2-AS1, LINC00632, MIR99AHG), 1 miRNA (hsa-miR-21-5p) and 5 targeted genes (RECK, TIMP3, EHD1, RASGRP1 and ERG) were figured out first. Through further Kaplan-Meier analysis screening the prognostic value, we finally found the hub subnetwork (MIR99AHG-hsa-miR-21-5p-EHD1) by collating lncRNA-miRNA pairs, miRNA-mRNA pairs and lncRNA-mRNA pairs. As the key of ceRNA regulatory network, the expression of miRNA-21-5p in lung cancer patients was significantly higher than that in healthy people (P < 0.01), and its high expression was significantly associated with poor prognosis (P = 0.0025). Our study successfully constructed a MIR99AHG-hsa-miR-21-5p-EHD1 mutually regulatory network, suggesting the potential efficient biomarkers in LC.

The significance of HAUS1 and its relationship with immune microenvironment in hepatocellular carcinoma.

Background: HAUS Augmin-like complex subunit 1(HAUS1), as a controlling gene, which affected the production of spindle was firstly discovered in Drosophila cells. Although HAUS1 has been intensively studied, but its significance and relationship with the immune microenvironment in Hepatocellular carcinoma (HCC) remain unclear. Materials and Methods: All data of HCC in this paper were obtained from The Cancer Genome Atlas(TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and the Human Protein Atlas(HPA) database. The role and potential value of HAUS1 in the tumorigenesis and development of HCC were studied by applying plenty of bioinformatics analysis methods. Knocked down the expression of HAUS1 through siRNA and further investigated the function of HAUS1 in HCC Results: HAUS1 was highly expressed in HCC, which led to a poor prognosis. ROC curve analysis showed that HAUS1 had a excellent diagnostic value. It was also associated with clinical stage, pathological grade and AFP of HCC. Univariate and multivariate COX regression analysis showed that HAUS1 was an independent prognostic factor for HCC patients. HAUS1 was associated with immune cells infiltrate and immune checkpoints in HCC, and it could generate significative therapeutic results when combined with anti-CTLA4 and anti-CD274 treatment. In vitro experiments, HAUS1 was found to promote the proliferation, invasion and metastasis, participated in cell cycle regulation and inhibited apoptosis of HCC. Conclusion: These results suggested that HAUS1 might serve as a potential therapeutic target, as well as a diagnostic, prognostic, and survival biomarker for HCC.

Mechanism through which the hsa-circ_0000992– hsa- miR- 936–AKT3 regulatory network promotes the PM2.5-induced inflammatory response in human bronchial epithelial cells

BackgroundStudies have shown that fine particulate matter (PM2.5) remains a significant problem in developing countries and plays a critical role in the onset and progression of respiratory illnesses. Circular RNAs (circRNAs) are involved in many pathophysiological processes,but their relationship to PM2.5 pollution is largely unexplored. ObjectivesTo elucidate the functional role of hsa_circ_0000992 in PM2.5-induced inflammation in a human bronchial epithelial cell line (16HBE) and to clarify whether the competing endogenous RNA (ceRNA) mechanism is involved in the interrelationships between hsa_circ_0000992 and hsa-miR-936 and the inflammatory signaling pathways. MethodsDetection of inflammatory factors in 16HBE cells exposed to PM2.5 by RT-qPCR and ELISA.High throughput sequencing and bioinformatics analysis methods were used to screen circRNA.The bioinformatics analysis method western blotting and dual-luciferase reporter gene system were used to verify mechanisms associated with circRNA. ResultsPM2.5 cause inflammation in the 16HBE cells. High throughput sequencing and RT-qPCR result revealed that the expression of hsa_circ_0000992 was markedly up-regulated in 16HBE exposed to PM2.5. The binding sites between hsa_circ_0000992 and hsa-miR-936 was confirmed by dual-luciferase reporter gene system.Western blotting and RT-qPCR showed that hsa_circ_0000992 can interact with hsa-miR-936 to regulate AKT serine/threonine kinase 3(AKT3),thereby activating the PI3K/AKT pathway and ultimately promoting the expression of interleukin (IL)− 1β and IL-8. ConclusionPM2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/AKT pathway. The expression of hsa_circ_0000992 increased when PM2.5 stimulated 16HBE cells,and the circRNA could then regulate the inflammatory response.Hsa_circ_0000992 regulates the hsa-miR-936/AKT3 axis through the ceRNA mechanism,thereby activating the PI3K/AKT signaling pathway,increasing the expression of cellular inflammatory factors,and promoting PM2.5-induced respiratory inflammation.

TMX family genes and their association with prognosis, immune infiltration, and chemotherapy in human pan-cancer.

The thioredoxin (TMX) system, an important redox system, plays crucial roles in several immune-related diseases. However, there is limited research on the correlation of TMX family gene expression with human pan-cancer prognosis, tumor microenvironment (TME), and immunotherapy. Based on the integration of several bioinformatics analysis methods, we explored the expression levels and prognostic value of TMX family members in pan-cancer and analyzed their association between TME, immune infiltration, stemness scores, and drug sensitivity. Using KEGG enrichment analysis, we explored the potential signaling pathways of their regulation. Additionally, we conducted a transwell assay to verify the relationship between TMX family gene expression and epithelial-mesenchymal transition (EMT) in liver cancer. Expression of the TMX family genes was shown to have an obvious intratumoral heterogeneity. In some cancers, TMX family members expression was also been found to correlate with poor prognosis of patients. Furthermore, TMX family genes may serve important roles in TME. The expression of TMX family genes was found to have a strong correlation with the stromal scores, immune scores, DNAss and RNAss in pan-cancer. Specifically, the expression levels of TMX family genes have been found to be associated with immune subtypes of renal clear cell carcinoma and liver hepatocellular carcinoma. High TMX2 expression promote EMT in liver cancer. The findings of this study may elucidate the biological roles of TMX family genes as potential targets for pan-cancer and also offer valuable insights for further investigating how these genes function in the development and spreading of cancer.