Critical Reviews in Eukaryotic Gene Expression最新文献

Dysregulated long noncoding RNAs (lncRNAs) promote the progression of osteosarcoma (OS). This study aimed to investigate the potential of lncRNA FGD5-AS1 in OS. Gene expression was determined using RT-qPCR. Protein expression was detected by western blot. N6-methyladenosine (m6A) modification was confirmed by MeRIP. Cell behaviors were detected using CCK-8, colony formation, and transwell assays. The interaction between miR-195-5p and the FGD5-AS1/SLC7A2 axis was confirmed by luciferase assays. FGD5-AS1 was upregulated in OS, induced by METTL16 via mediating m6A modification. However, FGD5-AS1 knockdown inhibited the proliferation and epithelial-mesenchymal transition (EMT) of OS cells. FGD5-AS1 sponged miR-195-5p to mediate the upregulation of SLC7A2, overexpression of which promoted aggressiveness of OS cells. In summary, METTL16-mediated upregulation of FGD5-AS1 promotes the aggressiveness of OS though targeting of miR-195-5p/SLC7A2 axis.

Cancer cells are a complex and robust system dynamically interconnected by the signaling genes network through the up-regulated AKT gene. How signals are transmitted still is not clear. The hyperphosphorylated AKT locus during protein-protein interaction sends infrared (IR) light as a signal to the other molecules and cells for cancer proliferation, migration, and angiogenesis. The hyperactivated AKT locus in cancer transmits IR light with a wavelength different from that in normal cells that is mechanistically characteristic of AKT-mediated control of cancer, recommended for targeting therapy by IR resonance. Thus, signaling is achieved by IR light. Such signaling is the first response of the hyperactivated AKT gene, far ahead of any biochemical response, activating the interactome network and creating a robust cancer system.

A growing number of women develop breast cancer and require surgery. Many lumpectomies lead to follow-up procedures after the initial surgery. Advanced scanning technologies have reduced the number of second and third surgeries, but only by about 50%. This paper assesses the potential of using multispectral images of intrinsic fluorescence to detect breast cancer. Images and spectra of intrinsic fluorescence from fresh ex vivo human specimens are related to pathological analysis, and predict high sensitivity and specificity. A design for a hand-held surgical scanning tool is presented.

Podocyte damage contributes to the progression of various renal diseases. This study aimed to investigate the effects of glycyrrhizin (GL) on podocyte injury. Puromycin aminonucleoside (PAN) was used to establish podocyte injury model in vitro. High throughput sequencing was applied for analyzing the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes was used to analyze the enrichment of DEGs. Gene expression was detected using Western blot and reverse transcription-quantitative PCR. The cytokine release was detected using enzyme-linked immunosorbent assay. Cytotoxicity was detected using lactate dehydrogenase assay. The death of podocytes was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry. We found that the DEGs after exposure to PAN were enriched in inflammatory signaling and autophagy. However, GL treatment suppressed the release of proinflammatory cytokines. GL treatment abrogated the effects of PAN and upregulated phosphorylated unc-51 like autophagy activating kinase 1, Beclin1, autophagy related 5, LC3B/A, lysosomal associated membrane protein 2, whereas downregulated sequestosome 1 and gasdermin D. Moreover, GL treatment suppressed the cytotoxicity induced by PAN as well as the pyroptosis of podocytes. However, 3-Methyladenine-mediated autophagy inhibition promoted the inflammation and pyroptosis of podocytes. In summary, GL exerts protective effects on PAN-induced podocyte injury. GL-mediated activation of autophagy suppresses inflammation and pyroptosis of podocytes. Therefore, GL may be a therapeutic strategy for podocyte injury.

FoxO proteins represent a subfamily of the forkhead box family (Fox) superfamily of proteins. It is involved in cell proliferation, differentiation, oxidative stress, apoptosis as well as tumors and metabolic disorders by regulating cellular functions. This paper aims to summarize the role of the transcription factor FoxO in type 2 diabetes and its complications, which may add to the potential of FoxO as a therapeutic target for future research. The transcription factor FoxO is expressed in various tissues and participates in various bodily functions including cell proliferation, differentiation, apoptosis, tumor therapy, and metabolic processes, playing a crucial role in the human body. FoxO plays a positive role in attenuating oxidative stress, inflammation, and metabolic disorders, which are the main causes of type 2 diabetes and its complications. FoxO plays an important role in the regulation of type 2 diabetes and its complications, and more precise targeting studies of FoxO will help to prevent, regulate, and treat diabetes-related diseases.

Circular RNAs (circRNAs) are intensively involved in the progression of atopic dermatitis (AD). This study investigated the role of circRHOBTB3 in AD. Human keratinocytes (HaCaT) were treated with interleukin 4 (IL-4) to establish an in vitro AD model. Gene expression was detected using reverse transcription-quantitative PCR (RT-qPCR) and Western blot. Cytokine release was detected using enzyme-linked immunosorbent assay (ELISA). The location of circRHOBTB3 was detected using RNA fluorescence in situ hybridization. The interaction between circRHOBTB3 and eukaryotic translation initiation factor 4A3 (EIF4A3) was detected using RNA immunoprecipitation and RNA pull-down assays. circRHOBTB3 and nuclear factor kappa B (NF-κB) interaction was confirmed using luciferase and chromatin immunoprecipitation assay. Cellular functions were determined via Cell Counting Kit 8 (CCK-8); and colony formation, wound healing, and transwell assays. circRHOBTB3 was overexpressed by TNF-α/IFN-γ treatment; however, its knock-down inhibited inflammatory response and suppressed proliferation of HaCaT cells induced by TNF-α/IFN-γ treatment. circRHOBTB3 binds to RNA binding protein EIF4A3 to activate NF-κB signaling. Moreover, NF-κB promotes transcription of circRHOBTB3. Additionally, overexpressed NF-κB promotes inflammatory response as well as the proliferation of HaCaT cells. Finally, the circRHOBTB3/EIF4A3/NF-κB axis forms a positive feedback loop in AD. Because its inhibition inhibits inflammatory response and proliferation of keratinocytes, targeting circRHOBTB3 may be a promising strategy for AD.

Background: Spinal tuberculosis (ST) poses a significant health risk as a severe infectious disease. MicroRNAs (miRNAs), key regulatory molecules, are implicated in the initiation and progression of ST. However, a comprehensive understanding of miRNA networks and their regulatory roles in ST remains insufficient.

Methods: Differential expression analysis of miRNAs between ST and healthy control (HC) samples was conducted using the GSE225679 dataset from the GEO database. Functional enrichment and transcription factor analyses were performed with FunRich software. To evaluate the diagnostic potential of the identified miRNAs, four machine learning models-support vector machine (SVM), random forest (RF), generalized linear model (GLM), and extreme gradient boosting (XGB)- were employed. A nomogram model was developed based on the optimal SVM results. In addition, in vitro experiments examined the impact of miR-1229-3p inhibition on cell proliferation, osteoclast formation (via TRAP staining), and the expression of inflammatory cytokines (IL-6, TNF-α, IL-1β, IL-17) using CCK-8, RT-qPCR, and Western blot techniques.

Results: A total of 257 differentially expressed miRNAs were identified, with 143 upregulated and 114 downregulated. Among the four models, SVM demonstrated the highest diagnostic accuracy, identifying five key miRNAs associated with ST (hsa-miR-4305, hsa-miR-3686, hcmv-miR-UL148D, ebv-miR-BHRF1-1, and hsa-miR-1229-3p). A miRNA-mRNA regulatory network was constructed, comprising 116 interaction pairs, involving three upregulated miRNAs and 57 downregulated target mRNAs. Additionally, a network of target genes and molecular drugs was established, which included 11 target genes and 224 candidate drugs. In vitro data showed that inhibiting miR-1229-3p significantly decreased cell proliferation, osteoclast formation, and the expression of IL-6, TNF-α, IL-1β, and IL-17 in tuberculin-stimulated cells.

Conclusion: This study offers new insights into the miRNA-mediated regulatory mechanisms in ST and highlights potential miRNA biomarkers for disease characterization.

This study aims to examine ferroptosis-associated genes in primary open-angle glaucoma (POAG) and offer new insights into the underlying disease mechanisms and potential therapeutic approaches. Differentially expressed genes (DEGs) between the POAG and control groups were identified using bioinformatics analysis and subsequently intersected with a ferroptosis gene set to isolate ferroptosis-related DEGs (Ferr DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to examine their biological functions. Core genes were identified through protein-protein interaction (PPI) network and Friends analysis. The diagnostic potential of core Ferr DEGs was assessed using receiver operating characteristic (ROC) curve analysis, while immune cell infiltration was examined using the CIBERSORT algorithm. Additionally, Spearman correlation analysis was used to examine the relationships between the identified genes and immune cell populations. A total of 25 Ferr DEGs were identified, with DDIT4, GDF15, NAMPT, HBA1, and IGFBP7 recognized as key core genes. ROC analysis demonstrated that these genes exhibited high diagnostic accuracy, with an AUC > 0.7. Additionally, the infiltration levels of memory B cells and macrophage_M2 were significantly elevated in POAG tissues compared to the control group. Notably, the core genes revealed significant correlations with various immune cell types. Our findings underscore the involvement of ferroptosis-related genes in POAG pathogenesis and highlight their potential as diagnostic biomarkers and therapeutic targets. Future research should focus on validating these findings in clinical settings and exploring the therapeutic modulation of ferroptosis in POAG management.

Inducing ferroptosis has become a means of hindering lung cancer progression. Curcumin regulates ferroptosis and participates in lung cancer progression, yet its mechanism on ferroptosis remains unclear. Semaphorin-6A attenuates lung cancer cell migration through the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 gene (HMOX1) axis. Therefore, the study investigated the mechanism of curcumin inhibiting the malignant progression of lung cancer cells by regulating ferroptosis via the NRF2/HMOX1 pathway. A549 and H209 cell viability, proliferation, death, invasion and migration were assessed by CCK-8, colony formation, lactate dehydrogenase, and Transwell assays. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and Fe2+, glutathione peroxidase 4 (GPX4), nuclear NRF2, and HMOX1, and NRF2 nuclear translocation were measured by kits, Western blot and immunofluorescence. Cell viability, proliferation, invasion and migration were decreased after curcumin treatment, while cell death was significantly increased (all P < 0.01). Curcumin-treated cells showed elevated ROS, MDA and Fe2+ levels, decreased SOD, GSH and GPX4 levels (all P < 0.01), and increased nuclear NRF2 level and nuclear translocation, and HMOX1 expression (all P < 0.01), suggesting that curcumin activated the NRF2/HMOX1 pathway to promote ferroptosis, thereby inhibiting lung cancer cell malignant progression. Liproxstatin-1 or ML385 treatment reversed curcumin-induced anti-tumor effect and ferroptosis. Curcumin activates the NRF2/HMOX1 pathway to promote ferroptosis, thus repressing the malignant progression of lung cancer cells. These findings provide new insights into the mechanism of curcumin's anti-tumor effect and highlight its potential as a therapeutic drug for lung cancer.

Abnormal levels of homocysteine (Hcy) and potassium are associated with poor prognosis of patients with ischemic stroke. Nonetheless, the roles Hcy and potassium in the prognosis of patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis (IVT) with recombinant tissue-type plasminogen activator (rt-PA) are still unknown. Therefore, the purpose of this study is to investigate the association between the levels of Hcy and potassium and clinical prognosis in AIS patients receiving IVT with rt-PA. AIS patients receiving IVT with rt-PA were enrolled in this study. AIS patients were divided into early neurological deterioration (END) and no END group according to the National Institutes of Health Stroke Scale (NIHSS) scores. Moreover, patients were divided into favorable outcome and poor outcome according to the modified Rankin Scale (mRS) scores. Multivariate logistic regression analysis was applied for detecting the risk factors. Four-hundred-twenty-six patients with AIS IVT with rt-PA were recruited: 24 patients showed END within 24 h. One-hundred-fifty-seven patients showed poor outcome. Multivariate analysis showed that higher levels of Hcy level (P < 0.001) and lower levels of potassium level (P < 0.01) were more frequently in patients with END and poor outcomes in AIS patients with IVT at the three-month visit. Taken together, the high Hcy and low potassium levels may be the potential biomarker for AIS patients receiving IVT with rt-PA.