Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.

Background: Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. Methods: AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. Results: In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. Conclusion: The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

Screening of Genes Associated with Immune Infiltration of Discoid Lupus Erythematosus Based on Weighted Gene Co-expression Network Analysis.

Discoid lupus erythematosus (DLE) is a disorder of the immune system commonly seen in women of childbearing age. The pathophysiology and aetiology are still poorly understood, and no cure is presently available. Therefore, there is an urgent need to explore the underlying molecular mechanisms, as well as search for new therapeutic targets. Gene expression data from skin biopsies samples of DLE patients and healthy controls were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between DLE and healthy control samples were identified by differential expression analysis. Samples were analysed using CIBERSORT to examine the proportion of immune infiltration. Weighted gene co-expression network analysis was used to screen for the module most relevant to immune infiltration. Candidate genes were uploaded to the TRRUST database to obtain the potential transcription factors regulating these genes. Protein-protein interaction (PPI) analysis was performed to obtain the hub genes most associated with immune infiltration among the candidate genes. A total of 273 DEGs were identified between the DLE and healthy control samples. The results of immunoinfiltration analysis showed that the abundances of resting memory CD4 T cells, activated memory CD4 T cells and M1 macrophages were significantly higher, while those of resting infiltration of plasma cells, regulatory T cells and dendritic cells were lower in DLE samples than in healthy control samples. Correlation analysis showed that ISG15, TRIM22, XAF1, IFIT2, OAS2, OAS3, OAS1, IFI44, IFI6, BST2, IFIT1 and MX2 were negatively correlated with the abundances of plasma cells, T-cell regulatory cells and resting dendritic cells and positively correlated with activated memory CD4 T cells and M1 macrophages. Our study shows that these hub genes may regulate DLE via immune-related pathways mediated by the infiltration of these immune cells.

Single Cell Sequencing Technology and Its Application in Alzheimer's Disease.

Alzheimer's disease (AD) involves degeneration of cells in the brain. Due to insidious onset and slow progression, AD is often not diagnosed until it gets progressed to a more severe stage. The diagnosis and treatment of AD has been a challenge. In recent years, high-throughput sequencing technologies have exhibited advantages in exploring the pathogenesis of diseases. However, the types of cells of the central nervous system are complex and traditional bulk sequencing cannot reflect their heterogeneity. Single-cell sequencing technology enables study at the individual cell level and has an irreplaceable advantage in the study of complex diseases. In recent years, this field has expanded rapidly and several types of single-cell sequencing technologies have emerged, including transcriptomics, epigenomics, genomics and proteomics. This review article provides an overview of these single-cell sequencing technologies and their application in AD.

The effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice.

OBJECTIVE: This study aimed to investigate the impact of esketamine on the intestinal flora and microenvironment in mice using mRNA transcriptome sequencing and 16S rRNA sequencing. METHODS: Ten female mice were randomly assigned to two groups. One group received daily intramuscular injections of sterile water, while the other group received esketamine. After 24 days, the mice were sacrificed, and their intestinal tissues and contents were collected for 16S rRNA sequencing and mRNA transcriptome sequencing. The intergroup differences in the mouse intestinal flora were analyzed. Differentially expressed genes were utilized to construct ceRNA networks and transcription factor regulatory networks to assess the effects of esketamine on the intestinal flora and intestinal tissue genes. RESULTS: Esketamine significantly altered the abundance of intestinal microbiota, including Adlercreutzia equolifaciens and Akkermansia muciniphila. Differential expression analysis revealed 301 significantly upregulated genes and 106 significantly downregulated genes. The ceRNA regulatory network consisted of 6 lncRNAs, 44 miRNAs, and 113 mRNAs, while the regulatory factor network included 13 transcription factors and 53 target genes. Gene Ontology enrichment analysis indicated that the differentially expressed genes were primarily associated with immunity, including B-cell activation and humoral immune response mediation. The biological processes in the ceRNA regulatory network primarily involved transport, such as organic anion transport and monocarboxylic acid transport. The functional annotation of target genes in the TF network was mainly related to epithelial cells, including epithelial cell proliferation and regulation. CONCLUSION: Esketamine induces changes in gut microbiota and the intestinal microenvironment, impacting the immune environment and transport modes.

Identification of mitochondrial-related genes as potential biomarkers for the subtyping and prediction of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder prevalent among older adults. Although AD symptoms can be managed through certain treatments, advancing the understanding of underlying disease mechanisms and developing effective therapies is critical. Methods: In this study, we systematically analyzed transcriptome data from temporal lobes of healthy individuals and patients with AD to investigate the relationship between AD and mitochondrial autophagy. Machine learning algorithms were used to identify six genes-FUNDC1, MAP1LC3A, CSNK2A1, VDAC1, CSNK2B, and ATG5-for the construction of an AD prediction model. Furthermore, AD was categorized into three subtypes through consensus clustering analysis. Results: The identified genes are closely linked to the onset and progression of AD and can serve as reliable biomarkers. The differences in gene expression, clinical features, immune infiltration, and pathway enrichment were examined among the three AD subtypes. Potential drugs for the treatment of each subtype were also identified. Discussion: The findings observed in the present study can help to deepen the understanding of the underlying disease mechanisms of AD and enable the development of precision medicine and personalized treatment approaches.

FGF21 promotes angiotensin II-induced abdominal aortic aneurysm via PI3K/AKT/mTOR pathway.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disorder with a high mortality rate. It was previously reported that fibroblast growth factor 21 (FGF21) was highly expressed in AAA patients. Nonetheless, its underlying mechanism in AAA progression is unclarified. METHODS: Angiotensin II (Ang-II) was used to induce AAA in human aortic vascular smooth muscle cells (HASMCs) and mouse models. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Immunofluorescence staining was utilized for detecting LC3B expression in HASMCs. Elastica van Gieson staining was conducted for histological analysis of the abdominal aortas of mice. RESULTS: FGF21 displayed a high level in Ang-II-stimulated HASMCs and AAA mice. FGF21 depletion ameliorated abdominal aorta dilation and Ang-II-triggered pathological changes in mice. FGF21 silencing hindered autophagy and PI3K/AKT/mTOR pathway. CONCLUSIONS: FGF21 contributes to AAA progression by enhancing autophagy and activating PI3K/AKT/mTOR pathway.

Effects of spaceflight on the spleen and thymus of mice: Gene pathway analysis and immune infiltration analysis.

During space flight, the immune system function of the body is disrupted due to continuous weightlessness, radiation and other factors, resulting in an increased incidence of infectious diseases in astronauts. However, the effect of space flight on the immune system at the molecular level is unknown. The aim of this study was to identify key genes and pathways of spatial environmental effects on the spleen and thymus using bioinformatics analysis of the GEO dataset. Differentially expressed genes (DEGs) in the spleen and thymus of mice preflight and postflight were screened by comprehensive analysis of gene expression profile data. Then, GO enrichment analysis of DEGs was performed to determine the biological role of DEGs. A protein-protein interaction network was used to identify hub genes. In addition, transcription factors in DEGs were screened, and a TF-target regulatory network was constructed. Finally, immune infiltration analysis was performed on spleen and thymus samples from mice. The results showed that DEGs in the spleen and thymus are mainly involved in immune responses and in biological processes related to platelets. Six hub genes were identified in the spleen and 13 in the thymus, of which Ttr, Aldob, Gc and Fabp1 were common to both tissues. In addition, 5 transcription factors were present in the DEGs of the spleen, and 9 transcription factors were present in the DEGs of the thymus. The spatial environment can influence the degree of immune cell infiltration in the spleen and thymus. Our study bioinformatically analyzed the GEO dataset of spacefaring mice to identify the effects of the space environment on the immune system and the genes that play key roles, providing insights for the treatment of spaceflight-induced immune system disorders.

Gene expression changes reveal the impact of the space environment on the skin of International Space Station astronauts.

BACKGROUND: The various types of ionizing radiation and altered gravity in the space environment present a risk to humans during space missions. Changes in the space environment lead to skin diseases, affecting the status of the aviators to fly. Therefore, it is important to explore the molecular-level changes in the skin during space missions. OBJECTIVES: Bioinformatics analysis of gene arrays from hair follicle tissue of 10 astronauts was performed to explore changes in gene expression before, during and after space missions. METHODS: First, STEM (Short Time-series Expression Miner) software was used to identify the expression patterns of hair follicle genes of astronauts pre-, in- and postflight. Gene Ontology Enrichment Analysis was then performed to explore the gene functions within the module. Protein-protein interaction network analysis was performed on skin-related genes. The transcriptional regulatory network within the module was constructed using the TRRUST database. The circadian rhythm-related genes within the module were screened using the MSigDB (Molecular Signatures Database). RESULTS: Based on differential expression analysis between the two groups, there were 327 differentially expressed genes after the astronauts entered space compared with preflight, and only 54 differentially expressed genes after returning to Earth. This outcome suggests that the expression of most genes can be recovered on return to the ground, but there are a small number of genes whose expression cannot be recovered in a short period of time. Based on time series analysis, 311 genes showed increased expression on entry into space and decreased expression on return to Earth. The genes of this expression pattern were associated with skin development, keratinocyte differentiation and cornification. Ten hub genes were identified as skin-related genes within the module, as well as nine transcription factors and three circadian genes. One hundred and seventy-nine genes decreased in expression after entry into space and increased on return to Earth. By reviewing the literature, we found that four of the genes, CSCD2, HP, CXCR1 and SSTR4, are associated with skin diseases. CONCLUSIONS: Through bioinformatics analysis, we found that the space environment affects skin keratinocyte differentiation, leading to skin barrier damage and inflammatory responses, and that this effect was decreased after return to Earth.

Rocuronium bromide suppresses esophageal cancer via blocking the secretion of C-X-C motif chemokine ligand 12 from cancer associated fibroblasts.

BACKGROUND: Cancer associated fibroblasts (CAFs) communicate metabolically with tumor genesis and development. Rocuronium bromide (RB) is reported to exert certain inhibitory effect on tumor. Here, we investigate the role of RB in esophageal cancer (EC) malignant progression. METHODS: Tumor xenograft models with EC cells were locally and systemically administrated with RB to detect the influence of different administrations on tumor progression. Mouse CAFs PDGFRα+/F4/80- were sorted by Flow cytometry with specific antibodies. CAFs were treated with RB and co-cultured with EC cells. The proliferation, invasion and apoptosis assays of EC cells were performed to detect the influences of RB targeting CAFs on EC cell malignant progression. Human fibroblasts were employed to perform these detections to confirm RB indirect effect on EC cells. The gene expression changes of CAFs response to RB treatment were detected using RNA sequencing and verified by Western blot, immunohistochemistry and ELISA. RESULTS: Tumors in xenograft mice were observed significantly inhibited by local RB administration, but not by systemic administration. Moreover EC cells did not show obvious change in viability when direct stimulated with RB in vitro. However, when CAFs treated with RB were co-cultured with EC cells, obvious suppressions were observed in EC cell malignancy, including proliferation, invasion and apoptosis. Human fibroblasts were employed to perform these assays and similar results were obtained. RNA sequencing data of human fibroblast treated with RB, and Western blot, immunohistochemistry and ELISA results all showed that CXCL12 expression was significantly diminished in vivo and in vitro by RB. EC cells direct treated with CXCL12 showed much higher malignancy. Moreover cell autophagy and PI3K/AKT/mTOR signaling pathway in CAFs were both suppressed by RB which can be reversed by Rapamycin pretreatment. CONCLUSIONS: Our data suggest that RB could repress PI3K/AKT/mTOR signaling pathway and autophagy to block the CXCL12 expression in CAFs, thereby weakening the CXCL12-mediated EC tumor progression. Our data provide a novel insight into the underlying mechanism of RB inhibiting EC, and emphasize the importance of tumor microenvironment (cytokines from CAFs) in modulating cancer malignant progression.

Immune infiltration and diagnostic value of immune-related genes in periodontitis using bioinformatics analysis.

BACKGROUND AND OBJECTIVES: Periodontitis, which is a chronic inflammatory periodontal disease resulting in destroyed periodontal tissue, is the leading cause of tooth loss in adults. Many studies have found that inflammatory immune responses are involved in the risk of periodontal tissue damage. Therefore, we analyzed the association between immunity and periodontitis using bioinformatics methods to further understand this disease. MATERIALS AND METHODS: First, the expression profiles of periodontitis and healthy samples were downloaded from the GEO database, including a training dataset GSE16134 and an external validation dataset GSE10334. Then, differentially expressed genes were identified using the limma package. Subsequently, immune cell infiltration was calculated by using the CIBERSORT algorithm. We further identified genes linking periodontitis and immunity from the ImmPort and DisGeNet databases. In addition, some of them were selected to construct a diagnostic model via a logistic stepwise regression analysis. RESULTS AND CONCLUSIONS: Two hundred sixty differentially expressed genes were identified and found to be involved in responses to bacterial and immune-related processes. Subsequently, immune cell infiltration analysis demonstrates significant differences in the abundance of most immune cells between periodontitis and healthy samples, especially in plasma cells. These results suggested that immunity doses play a non-negligible role in periodontitis. Twenty-one genes linking periodontitis and immunity were further identified. And nine hub genes of them were identified that may be key genes involved in the development of periodontitis. Gene ontology analyses showed that these genes are involved in response to molecules of bacterial origin, cell chemotaxis, and response to chemokines. In addition, three genes of them were selected to construct a diagnostic model. And its good diagnostic performance was demonstrated by the receiver operating characteristic curves, with an area under the curve of 0.9424 for the training dataset and 0.9244 for the external validation dataset.

Construction of a novel miRNA regulatory network and identification of target genes in gestational diabetes mellitus by integrated analysis.

Backgrounds: Given the roles of microRNA (miRNA) in human diseases and the high incidence of gestational diabetes mellitus (GDM), the aim of the study was to examine miRNA signatures and crucial pathways, as well as possible biomarkers for GDM diagnosis. Methods: We conducted a two-stage study to explore functional miRNA and those target genes. Twelve participants (6 GDM and 6 non-GDM) were first enrolled and performed RNA sequencing analysis. The overlapped candidate genes were further screened in combination with differentially expressed genes (DEGs) of GEO datasets (GSE87295, GSE49524 and GSE19649) and potential target genes of DEMs. Candidate genes, critical pathways, small molecular compounds and regulatory networks were identified using bioinformatic analysis. The potential candidate genes were then investigated using the GEO dataset (GSE103552) of 19 participants in the validation stage (11 GDM and 8 non-GDM women). Results: Briefly, blood samples were sequenced interrogating 50 miRNAs, including 20 upregulated and 30 downregulated differentially expressed microRNAs(DEMs) in our internal screening dataset. After screening GEO databases, 123 upregulated and 70 downregulated genes were overlapped through DEGs of GEO datasets and miRNA-target genes. MiR-29b-1-5p-TGFB2, miR-142-3p-TGFB2, miR-9-5p-FBN2, miR-212-5p-FBN2, miR-542-3p-FBN1, miR-9-5p-FBN1, miR-508-3p-FBN1, miR-493-5p-THBS1, miR-29b-3p-COL4A1, miR-432-5p-COL5A2, miR-9-5p-TGFBI, miR-486-3p-SLC7A5 and miR-6515-5p-SLC1A5 were revealed as thirteen possible regulating pathways by integrative analysis. Conclusion: Overall, thirteen candidate miRNA-target gene regulatory pathways representing potentially novel biomarkers of GDM diseases were revealed. Ten chemicals were identified as putative therapeutic agents for GDM. This study examined a series of DEGs that are associated with epigenetic alternations of miRNA through an integrated approach and gained insight into biological pathways in GDM. Precise diagnosis and therapeutic targets of GDM would be further explored through putative genes in the future.

A prognostic and therapeutic hallmark developed by the integrated profile of basement membrane and immune infiltrative landscape in lung adenocarcinoma.

Basement membranes (BMs) are specialised extracellular matrices that maintain cellular integrity and resist the breaching of carcinoma cells for metastases while regulating tumour immunity. The tumour immune microenvironment (TME) is essential for tumour growth and the response to and benefits from immunotherapy. In this study, the BM score and TME score were constructed based on the expression signatures of BM-related genes and the presence of immune cells in lung adenocarcinoma (LUAD), respectively. Subsequently, the BM-TME classifier was developed with the combination of BM score and TME score for accurate prognostic prediction. Further, Kaplan-Meier survival estimation, univariate Cox regression analysis and receiver operating characteristic curves were used to cross-validate and elucidate the prognostic prediction value of the BM-TME classifier in several cohorts. Findings from functional annotation analysis suggested that the potential molecular regulatory mechanisms of the BM-TME classifier were closely related to the cell cycle, mitosis and DNA replication pathways. Additionally, the guiding value of the treatment strategy of the BM-TME classifier for LUAD was determined. Future clinical disease management may benefit from the findings of our research.

Effects of the Targeted Regulation of CCRK by miR-335-5p on the Proliferation and Tumorigenicity of Human Renal Carcinoma Cells.

Cell cycle-related kinase (CCRK) is most closely related to cyclin-dependent protein kinase, which may activate cyclin-dependent kinase 2 and is associated with the growth of human cancer cells. However, the expression and function of CCRK in the pathogenesis of clear cell renal cell cancer (ccRCC) are unclear. Herein, this research aimed to explore the potential mechanism of the targeted regulation of CCRK by miR-335-5p on the proliferation and tumorigenicity of human ccRCC cells. The results showed that CCRK was significantly overexpressed in ccRCC tissues and cells, and knockdown of the CCRK expression by shRNA inhibited cell proliferation in vitro and in vivo and enhanced cell apoptosis in vitro, which indicated that CCRK could be a potential target for antitumour drugs in the treatment of ccRCC. Moreover, miR-335-5p was found to bind directly to the 3' untranslated region of CCRK, was expressed at markedly low levels in ccRCC cells, and was closely associated with the tumour stage. The overexpression of CCRK partially reversed the inhibitory effects of miR-335-5p on the cell growth of ccRCC, which implied that miR-335-5p could serve as a promising tumour inhibitor for ccRCC. In summary, CCRK could serve as an alternative antitumour drug target, and miR-335-5p could be a promising therapeutic tumour inhibitor for ccRCC treatment.

The complete chloroplast genome of Strobilanthes crispus (Acanthaceae).

We reported and characterized the complete chloroplast genome sequence of Strobilanthes crispus Blume 1826. Strobilanthes crispus belongs to the Acanthaceae family and has a number of local names including Batuzin, Bayam Karang, Kotz Bellin, and Pekka Batu, which is native to Malaysian with diverse beneficial uses. Green leaves were determined using next-generation sequencing. We found that the entire chloroplast genome of S. crispus was 144,987 bp in length, included four segments, named a large single-copy (LSC) region (92,556 bp), a small single-copy (SSC) region (17,783 bp), and a pair inverted repeat regions (IRs) (17,324 bp in each), respectively. The chloroplast genome of S. crispus contained a total of 129 functional genes, including 84 protein-coding genes, 37 transfer RNAs (tRNAs), and eight ribosomal RNA (rRNA) genes. The phylogenetic tree reconstructed by nine chloroplast genomes reveals that S. crispus is most closely related to Strobilanthes bantonensis and Strobilanthes cusia.

The Effects and Mechanisms of Sennoside A on Inducing Cytotoxicity, Apoptosis, and Inhibiting Metastasis in Human Chondrosarcoma Cells.

Currently, developing therapeutic strategies for chondrosarcoma (CS) remains important. Sennoside A (SA), a dianthrone glycoside from Senna and Rhubarb, is widely used as an irritant laxative, weight-loss agent, or dietary supplement, which possesses various bioactive properties such as laxative, antiobesity, and hypoglycemic activities. For the first time, our results suggested that cell proliferation and metastasis were inhibited by SA in CS SW1353 cells. SA induced cell growth arrest by inhibiting cell proliferation. The changes of N-cadherin and E-cadherin levels, the markers associated with epithelial mesenchymal transition (EMT), suggested the EMT-related mechanism of SA in inhibiting cell metastasis. Besides, SA significantly stimulated apoptosis in CS SW1353 cells, leading to cell death. The increase of Bax/Bcl2 ratio confirmed that the internal mitochondrial pathway of apoptosis was regulated by SA. In addition, the prediction of network pharmacology analysis suggested that the possible pathways of SA treatment for CS included the Wnt signaling pathway. Notably, the protein levels of the components in the Wnt pathway, such as Wnt3a, ß-catenin, and c-Myc, were downregulated by SA in CS SW1353 cells. To sum up, these results demonstrated that the suppression of the growth, metastasis and the stimulation of cytotoxicity, and apoptosis mediated by SA in CS SW1353 cells were possibly caused by the inhibition of the Wnt/ß-catenin pathway, indicating an underlying therapeutic prospect of SA for chondrosarcoma.

Corrigendum: Prognostic ferroptosis-related lncRNA signatures associated with immunotherapy and chemotherapy responses in patients with stomach cancer.

[This corrects the article DOI: 10.3389/fgene.2021.798612.].

Immunological and prognostic analysis of PSENEN in low-grade gliomas: An immune infiltration-related prognostic biomarker.

Metformin is widely used in the treatment of type 2 diabetes (T2D) and plays a role in antitumor and antiobesity processes. A recent study identified its direct molecular target, PEN2 (PSENEN). PSENEN is the minimal subunit of the multiprotein complex γ-secretase, which promotes the differentiation of oligodendrocyte progenitors into astrocytes in the central nervous system. This study was mainly based on gene expression data and clinical data from the TCGA and CGGA databases. Analysis of differential expression of PSENEN between tissues from 31 cancers and paracancerous tissues revealed that it had high expression levels in most cancers except 2 cancers. Using univariate Cox regression analysis and Kaplan-Meier survival analysis, a high expression level of PSENEN was shown to be a risk factor in low-grade gliomas (LGG). Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses indicated that PSENEN is widely involved in immune-related signaling pathways in LGG. PSENEN expression level was significantly associated with TMB, MSI, tumor stemness index, and the expression levels of immunomodulatory genes in LGG. Finally, immune infiltration analysis revealed that PSENEN level was associated with the presence of various immune infiltrating cells, among which PSENEN was strongly associated with the presence of M2 macrophages and played a synergistic pro-cancer role. In conclusion, PSENEN may partially influence prognosis by modulating immune infiltration in patients with LGG, and PSENEN may be a candidate prognostic biomarker for determining prognosis associated with immune infiltration in LGG.

Corrigendum: Analysis of time series gene expression and DNA methylation reveals the molecular features of myocardial infarction progression.

[This corrects the article DOI: 10.3389/fcvm.2022.912454.].

The Long Noncoding RNA MEG3 Retains Epithelial-Mesenchymal Transition by Sponging miR-146b-5p to Regulate SLFN5 Expression in Breast Cancer Cells.

More and more studies have shown that long noncoding RNAs (lncRNAs) play essential roles in malignant tumors. The lncRNA MEG3 serves as a crucial molecule in breast cancer development, but the specific molecular mechanism needs to be further explored. We previously reported that Schlafen family member 5 (SLFN5) inhibits breast cancer malignant development by regulating epithelial-mesenchymal transition (EMT), invasion, and proliferation/apoptosis. Herein, we demonstrated that MEG3 was downregulated in pan-cancers and correlated with SLFN5 expression positively in breast cancer by bioinformatics analysis of TCGA and UCSC Xena data. Intervention with MEG3 positively affected SLFN5 expression in breast cancer cells. MEG3 repressed EMT and migration/invasion, similar to our previously reported functions of SLFN5 in breast cancer. Through bioinformatics analysis of starBase and LncBase data, 12 miRNAs were found to regulate both SLFN5 and MEG3, in which miR-146b-5p was confirmed to be regulated by MEG3 using MEG3 siRNA and overexpression method. MiR-146b-5p could bind to both SLFN5 3'UTR and MEG3, and inhibit their expression in a competing endogenous RNA mechanism, assayed by luciferase reporter and RNA pull down methods. Therefore, we conclude that MEG3 positively modulates SLFN5 expression by sponging miR-146b-5p and inhibits breast cancer development.

Activating transcription factor 4 aggravates angiotensin II-induced cell dysfunction in human vascular aortic smooth muscle cells via transcriptionally activating fibroblast growth factor 21.

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-II-induced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch. ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.