关键词： Breast cancer   TGF-beta 1   ATF3   Non-coding RNAs   MicroRNAs   Circular RNAs  

摘要： A potent growth inhibitor for normal mammary epithelial cells is transforming growth factor beta 1 (TGF-beta 1). When breast tissues lose the anti-proliferative activity of this factor, invasion and bone metastases increase. Human breast cancer (hBC) cells express more activating transcription factor 3 (ATF3) when exposed to TGF-beta 1, and this transcription factor is essential for BC development and bone metastases. Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and microRNAs (miRNAs), have emerged as key regulators controlling several cellular processes. In hBC cells, TGF-beta 1 stimulated the expression of hsa-miR-4653-5p that putatively targets ATF3. Bioinformatics analysis predicted that hsa-miR-4653-5p targets several key signaling components and transcription factors, including NFKB1, STAT1, STAT3, NOTCH1, JUN, TCF3, p300, NRF2, SUMO2, and NANOG, suggesting the diversified role of hsa-miR-4653-5p under physiological and pathological conditions. Despite the high abundance of hsa-miR-4653-5p in hBC cells, the ATF3 level remained elevated, indicating other ncRNAs could inhibit hsa-miR-4653-5p's activity. In silico analysis identified several circRNAs having the binding sites for hsa-miR-4653-5p, indicating the sponging activity of circRNAs towards hsa-miR-4653-5p. The study's findings suggest that TGF-beta 1 regulates circRNAs and hsa-miR-4653-5p, which in turn affects ATF3 expression, thus influencing BC progression and bone metastasis. Therefore, focusing on the TGF-beta 1/circRNAs/hsa-miR-4653-5p/ATF3 network could lead to new ways of diagnosing and treating BC.

关键词： ATF3   Ferritin   RNA expression   Osteoarthritis   Immune infiltration   RNA analysis method  

摘要： Osteoarthritis (OA) is a widespread joint disorder that is primarily noted for the progressive degeneration of joint cartilage, accompanied by a significant inflammatory response. Recently, there has been a growing interest in understanding the roles of ATF3 and ferritin-related RNAs in the context of immune responses and inflammatory processes. However, their specific functions and mechanisms in the progression of osteoarthritis have remained largely ambiguous and underexplored. The primary objective of this study was to thoroughly investigate the changes in expression levels of ATF3 and ferritin-related RNAs within osteoarthritic tissues, as well as to examine their potential effects on immune cell infiltration. To achieve this, advanced RNA sequencing technology was employed to meticulously analyze the expression levels of ATF3 and the ferritin-related RNAs. Furthermore, bioinformatics methods were utilized to assess the infiltration patterns of various immune cells and to explore the correlation between these infiltration patterns and the expression levels of RNA. The findings from this study revealed that both ATF3 and ferritin-related RNAs exhibited significantly elevated expression levels in tissues affected by osteoarthritis. Additionally, the immunoinfiltration analysis highlighted a positive correlation between the degree of infiltration of T cells and macrophages and the levels of ferritin-related RNAs. Such findings suggest that the presence of these immune cells is intricately linked to the expression of ferritin-associated RNAs. Further investigations indicated that ferritin-associated RNAs play a critical role in the progression of osteoarthritis by modulating inflammatory responses and influencing the activity of various immune cells. Consequently, both ATF3 and ferritin-related RNAs demonstrate abnormal expression patterns in osteoarthritis, which are closely associated with the infiltration of immune cells.

关键词： Micro RNA-490-3p (miR-490-3p)   nucleolar and spindle-associated protein 1 (NUSAP1)   osteosarcoma   apoptosis   cell-cycle arrest  

摘要： Background: Micro RNA-490-3p (miR-490-3p) is associated with a variety of malignancies. However, the role of miR-490-3p in osteosarcoma and its underlying mechanism are not yet fully understood. This study aimed to explore the role and the mechanism of miR-490-3p in ***: MiR-490-3p and nucleolar and spindle-associated protein 1 (NUSAP1) expression in osteosarcoma was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), wound-healing, and transwell assays were used to detect cell proliferation, migration and invasion. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot were used to evaluate the cell apoptosis. Flow cytometry was used to assess the cell cycle. In addition, luciferase reporter assay was used to confirm the binding of miR-490-3p and NUSAP1. Western blot and RT-qPCR was used to examine cell division cycle associated 8 (CDCA8) and activating transcription factor 3 (ATF3) ***: MiR-490-3p expression was significantly decreased in the osteosarcoma cells. Following the transfection with miR-490-3p mimic, it was found that 143B cell proliferation, migration, and invasion were inhibited, while the cell apoptotic levels and cell-cycle arrest were promoted, accompanied with decreased B cell lymphoma protein-2 (Bcl-2) protein expression, and increased protein expressions of Bcl-2-associated X (Bax), cleaved caspase-3, and cleaved caspase-9. In addition, miR-490-3p was found to bind to NUSAP1, and negatively regulate NUSAP1 expression. NUSAP1 upregulation reversed the inhibitory effects of miR-490-3p overexpression on cell proliferation, migration, and invasion, and the promoting effects on cell apoptosis and cell-cycle arrestin osteosarcoma. Moreover, miR-490-3p was identified to mediate CDCA8/ATF3 by targeting ***: MiR-490-3p upregulation inhibited cell proliferation and metastasis but promoted the cell apoptosis and cell-cycle arre

关键词： 1 alpha   25-hydroxyvitamin D 3   Rotavirus   Ferroptosis   IPEC-J2 cell  

摘要： Rotavirus (RV) mainly infects mature intestinal epithelial cells and impairs intestinal absorption function, which leads to the death of infected cells and eventually fatal diarrhea. Ferroptosis is a novel regulatory cell death pattern, which can be caused by virus infection. 1 alpha,25-hydroxyvitamin D3 (1,25D3) has an anti-RV infection effect and can regulate ferroptosis. However, whether RV infection can induce ferroptosis, and whether 1,25D3 can inhibit RV infection by regulating ferroptosis has not yet been studied. Present study shows that RV infection or erastin treatment induces IPEC-J2 cell death, which results in mitochondrial shrinkage, decreased mitochondrial membrane potential (MMP) and glutathione (GSH) content, increased MMP, intracellular Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) contents. Meanwhile, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), and deferoxamine (DFO) treatment can effectively reverse the increase of intracellular Fe2+, ROS and MDA levels induced by RV infection. Moreover, RV infection increases activating transcription factor 3 (ATF3) mRNA and protein expressions, and inhibited SLC7A11 and glutathione peroxidase 4 (GPX4) expressions, which was partially alleviated by siATF3. 1,25D3 treatment significantly eliminates RV induced ferroptosis via ATF3-SLC7A11-GPX4 axis. Therefore, these results reveals that RV infection induces ferroptosis in IPEC-J2 cell and 1,25D3 alleviates RV induced ferroptosis by regulating the ATF3-SLC7A11-GPX4 axis.

关键词： Acute lung injury   Alveolar macrophages   Activating transcription factor 3   NLRP3   Inflammation   Pyroptosis  

摘要： Background: Acute lung injury (ALI) ranks among the leading reasons for death in septic patients. As an essential transcription factor associated with stress, activating transcription factor 3 (ATF3) participates in a variety of pathophysiological processes, including immunology and inflammation. However, the specific mechanism of ATF3 in pyroptosis of sepsis-induced ALI remains elusive. Methods: A mouse model of ALI was established by administering lipopolysaccharide (LPS) in vivo and LPS combined with adenosine triphosphate (ATP) in vitro to compare differences in ATF3 expression level. The role of ATF3 in pyroptosis was then assessed by knocking down ATF3 using small interfering RNA. The levels of interleukin-6 (IL-6), tumor necrosis factor-alpha, IL-1 beta, and IL-18 in mouse serum and cell culture supernatants were measured using enzyme-linked immunosorbent assay. Moreover, immunohistochemistry, immunofluorescence, Western blotting, co-immunoprecipitation, and quantitative reverse transcription polymerase chain reaction were employed for examining pyroptosis and pyroptotic pathways. Results: Both in vitro and in vivo ALI models were successfully established. LPS could activate the pyroptotic signaling pathway, and the expression level of ATF3 peaked 6 h after LPS and ATP stimulation in vitro. ATF3 could interact with NLRP3 and potentially influence the assembly of the inflammasome. This mechanism could involve the inhibition of the classical pyroptotic pathway, including Caspase-1 and Gasdermin D transcription and cleavage, as well as the inhibition of the non-classical pyroptotic pathway, including transcription and cleavage of Caspase-11. Conclusion: The results indicated that inhibition of ATF3 could exacerbate sepsis-induced ALI by regulating pyroptotic pathways. The potential of targeting ATF3 as a future treatment strategy for ALI is noteworthy.

关键词： Crassostrea gigas   Granulocytes   Transcription signature ATF3   Transcriptional activator   Phagocytic capacity  

摘要： Phagocytosis is a major cellular mechanism for mollusk granulocytes to eliminate nonself substances and dead cells, and thus to preserve the immune homeostasis. The knowledge of the regulatory mechanisms controlling phagocytic capacity is vital to understanding the immune system. In the present study, an ATF3 homolog (CgATF3) with a typical bZIP domain was identified in the Pacific oyster Crassostrea gigas. Its highly conserved bZIP domain consisted of two structural features, a basic region for DNA binding and a leucine zipper region for dimerization. Its transcript was found to be abundantly expressed in haemocytes, which was induced by Vibrio splendidus stimulation and recombinant CgTNF-2 treatment, along with an increase of its protein content in the nucleus. Moreover, CgATF3 showed a consistent and specific high expression in granulocytes, and CgATF3+ granulocytes were characterized morphologically by the largest diameter, smaller nucleus to cytoplasmic ratio, and abundant cytoplasmic granules, and functionally by a higher capacity for phagocytosis. When CgATF3 expression was inhibited by RNAi, the expression levels of CgRab1, CgRab33 and CgCathepsin L1, as well as the phagocytic rate and index of granulocytes all decreased after V. splendidus stimulation. These results together demonstrated the involvement of CgATF3 in regulating the expressions of Rabs and Cathepsin L1, as well as the phagocytosis of granulocytes in oyster C. gigas.

关键词： Gout   Ferroptosis   Bioinformatics   Machine learning   Biomarkers  

摘要： Objective Gout is a prevalent form of chronic inflammatory arthritis, and its etiology remains incompletely understood. Ferroptosis is a form of cell death that relies on iron. As of now, the relationship between ferroptosis and gout is not entirely clear. Hence, the primary objective of this study is to employ bioinformatics methods for the analysis and identification of potential genes associated with ferroptosis in the context of gout. Methods Utilizing both bioinformatics analysis and machine learning algorithms to systematically identify biomarkers for gout. The gout-related dataset (GSE160170) was acquired from the Gene Expression Omnibus (GEO) database. Ferroptosis-related genes were extracted from the FerrDb database. subsequently, we identified DEGs associated with ferroptosis in the context of gout. Following that, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on the DEGs. Subsequently, SVM-RFE analysis and the LASSO regression model were employed for biomarker screening. Additionally, CIBERSORT software was utilized to assess the composition of twenty-two immune cells in gout, and correlation analyses between hub genes and immune cells were conducted. Results This study screened a total of twenty-five DEGs related to Ferroptosis in healthy population and gout patient. The KEGG analysis indicates that these DEGs are predominantly enriched in: the AGE-RAGE signaling pathway, nod like receptor signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, etc. The intersection of the top 10 genes identified through PPI network, SVM-RFE analysis, and LASSO regression model resulted in two hub genes, namely JUN and ATF3. Analysis of immunocyte infiltration revealed that JUN exhibited associations with various immune cells, including NK cells resting, Monocytes, Mast cells resting, etc. ATF3, on the other hand, showed associations with immune cells Mast cells resting and Eosinophels. Conclusi

关键词： LINC00894   ATF3   Proliferation   Apoptosis  

摘要： LINC00894 may be associated with synaptic function, but its biology function in neural cells is still unknown. In this study, LINC00894 knockdown decreased the EdU incorporated into newly synthesized DNA and cell viability in MTT or CCK-8 assay in HEK-293T and BE(2)-M17 (M17) neuroblastoma cells. And LINC00894 knockdown increased cellular apoptosis in Annexin V-FITC staining, the expression of activated Caspase3 and the level of reactive oxygen species (ROS) both in HEK-293T and M17 cells. Moreover, LINC00894 also protected cells from hydrogen peroxide induced apoptosis in in vitro models. Utilizing RNA sequencing (RNA-seq) integrated with quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoblot, we identified that LINC00894 affected activating transcription factor 3 (ATF3) expression in HEK-293T, M17, and SH-SY5Y neuroblastoma cells. Finally, we found that ectopic expression of ATF3 restored cell proliferation and inhibited cell apoptosis in LINC00894 downregulated M17 cells. While knockdown of ATF3 also significantly increased the cell viability inhibition and apoptosis promotion induced by LINC00894 knockdown in M17 cells. Our results from in vitro models revealed that LINC00894 could promote neuronal cell proliferation and inhibit cellular apoptosis by affecting ATF3 expression.

关键词： FOXP4-AS1   LncRNA   Cancer   Biological function   Molecular mechanism   AKT   Protein kinase B   ANRIL   Antisense non-coding RNA in the INK4 Locus   AR   Androgen receptor   ASO   Antisense oligonucleotide   ATF3   Activating transcription factor 3   BBOX1-AS1   BBOX1 antisense RNA 1   CA125   Carbohydrate antigen 125   CA19-9   Cancer antigen 19-9   CBX4   Chromobox protein homolog 4   CC   Cervical cancer   CEA   Carcinoembryonic antigen   CEBPA-AS1   CCAAT enhancer binding protein alpha antisense RNA 1   ceRNA   Competing endogenous RNA   ChIP   Chromatin Immunoprecipitation   CHOL   Cholangiocarcinoma   COAD   Colon adenocarcinoma   CRC   Colorectal cancer   CTCF   CCCTC-binding factor   CYFRA21-1   Cytokeratin 19 fragment 21-1   DFS   Disease-free survival   DLBC   Diffuse large B-cell lymphoma   DLG5-AS1   Discs large homolog 5 antisense RNA 1   DSS   Disease-specific survival   DUSP5   Dual specificity phosphatase 5   EEC   Endometrial cancer   EFS   Event-free survival   EIF5A   Eukaryotic translation initiation factor 5A   EMT   Epithelial-mesenchymal transition   eRNA   Enhancer RNA   ES   Ewing's sarcoma   ESCA   Esophageal carcinoma   ESCC   Esophageal squamous cell carcinoma   ESR1   Estrogen receptor 1   EZH2   Enhancer of zeste homolog 2   FOXA1   Forkhead box protein A1   FOXP4   Forkhead box protein P4   FOXP4-AS1   FOXP4 antisense RNA 1   GC   Gastric cancer   H3K27me3   Histone H3K27 trimethylation   H3K4me2   Histone H3K4 dimethylation   H3K4me3   Histone H3K4 trimethylation   HCC   Hepatocellular carcinoma   IGF2BP2   Insulin-like growth factor 2 mRNA-binding protein 2   INHBA-AS1   Inhibin beta A antisense RNA 1   LAML   Acute myeloid leukemia   LATS1   Large tumor suppressor kinase 1   LGG   Lower grade glioma   LINC01140   Long intergenic non-coding RNA 1140   LINC01559   Long intergenic non-coding RNA 01559   LITATS1   Long intergenic transcript activating TATS1   LncRNA   Long non-coding RNA   LSD1   Lysine specific demethylase1   MAPK1   Mitogen-activated protein kinase 1   MCL   Mantle cell lymphoma   MESO   Mesothelioma   MIR4435-2HG   MicroRNA 4435 host gene 2   miRNA   microRNA   MLL2   Mixed lineage leukemia 2   mRNA   messenger RNA   MS   Median survival   NACC1   Nucleus accumbens-associated protein 1   NPC   Nasopharyngeal car  

摘要： Forkhead box P4 antisense RNA 1 (FOXP4-AS1) is a long non-coding RNA (lncRNA) situated on the human chromosome 6p21.1 locus. Previous research has demonstrated that FOXP4-AS1 is dysregulated in various cancers and exhibits a dual purpose as a tumor suppressor or oncogene in specific types of cancer. The levels of FOXP4-AS1 are significantly correlated with clinical features of cancer as well as prognosis. Additionally, FOXP4-AS1 is stimulated by transcription factors ATF3, YY1, PAX5, and SP4. The molecular mechanisms of FOXP4-AS1 in cancer are quite complex. It competitively sponges multiple miRNAs, bidirectionally regulates the levels of host gene FOXP4, activates the PI3K/AKT, Wnt/β-catenin, and ERK/MAPK signaling pathways, and recruits chromatin-modifying enzymes or interacts with other proteins to regulate malignant phenotypes of tumors, including proliferation, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis. In this review, we provide an overview of the latest developments in FOXP4-AS1 oncology research, outlines its molecular regulatory networks in cancer, and discusses its prospective relevance as a cancer therapeutic target as well as a biomarker for prognosis and diagnosis.