Critical Reviews in Eukaryotic Gene Expression最新文献

RNA methylation is involved in the pathogenesis of ankylosing spondylitis (AS). This study aimed to investigate the potentials of METTL17 in AS. mRNA expression was detected using RT-qPCR. RNA methylation was detected using MeRIP assay. Protein expression was detected using western blot. Cell proliferation was detected using EdU assay. Macrophage functions was detected using flow cytometry. METTL17 was upregulated after exposure to LPS. However, METTL17 knockdown promoted inflammatory response. Moreover, METTL17 knockdown promoted M1 macrophage polarization. Mechanically, METTL17 regulate RNA methylation. Mechanically, METTL17 promoted the RNA methylation of STAT1, inhibiting the mRNA and protein stability of STAT1. In summary, METTL17 inhibits inflammatory response and M1 macrophage polarization via mediating the RNA methylation of STAT1. Therefore, targeting METTL17/STAT1 may be a promising strategy for AS.

This study aimed to investigate the potential effects and underlying mechanism of plumbagin (PL) on the proliferation and apoptosis of SU-DHL-4 cells, a type of diffuse large B-cell lymphoma (DLBCL), through in vitro and in vivo experiments. The in vitro experiments were performed by subjecting SU-DHL-4 cells to different concentrations of PL. The proliferation rate of the cells was evaluated using the CCK8 assay. Flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), and a commercial ROS detection kit were employed to quantify the apoptosis rate, the antioxidant enzyme activity, and the levels of reactive oxygen species (ROS), respectively. The protein expression of Bax, BCL2, caspase-3, cleaved caspase-3, PI3K, p-PI3K, Akt, p-Akt, mTOR, and p-mTOR were determined by western blotting. The cell-derived tumor xenograft tumor model was constructed by subcutaneously injecting SU-DHL-4 cells into NOD-SCID mice. The therapeutic effect of PL was then evaluated by morphological staining. Results from the in vitro experiments demonstrated that PL could effectively inhibit cell proliferation, increase the production of reactive oxygen species (ROS), and induce apoptosis in SU-DHL-4 cells in both a time- and a dosage-dependent manner. Furthermore, PL treatment upregulated the protein expression of Bax and cleaved caspase-3 (P < 0.05). In parallel, PL treatment concurrently DOWNREGULATED the protein expression of Bcl-2, p-PI3K, p-Akt, and p-mTOR (P < 0.05). More important, it inhibits the growth of mouse xenograft tumors. PL promotes apoptosis of DLBCL cells, potentially by upregulating ROS and suppressing the PI3K/Akt/mTOR signaling pathway. These findings might be a useful reference for future drug discovery.

Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies, and understanding the molecular mechanisms underlying its development is essential for improving diagnosis and treatment. However, the role of DNA methylation, a key epigenetic modification, in UCEC prognosis prediction and clinical treatment strategies has rarely been studied. This study utilized publicly available datasets from The Cancer Genome Atlas (TCGA) and online bioinformatics tools to analyze the differential methylation and expression of six selected genes: TP53, PTEN, PTX3, TNK1, PPP2R1A, and KLRG2. These genes were chosen based on their known roles in cancer-related pathways, previous associations with oncogenic processes, and preliminary data showing significant changes in methylation and expression in UCEC compared with normal tissues. We integrated mRNA expression and DNA methylation data with the MethylMix method to identify genes with methylation-driven expression changes. Our analysis revealed that these genes exhibit distinct differential expression and methylation patterns in UCEC, suggesting potential regulatory mechanisms. The expression patterns across the six genes were observed, and TP53, TNK1, PPP2R1A, and KLRG2 were upregulated in tumors, and PTX3 was downregulated in tumors. At the same time, there was no significant change in the expression of PTEN gene. The differential expression correlates with changes in methylation, providing insights into the gene regulation occurring in UCEC. Additionally, Kaplan-Meier survival analysis revealed that the expression levels of specific genes, particularly PTX3, TNK1, and KLRG1, are significantly associated with overall survival in UCEC patients. Higher expression of these genes correlated with poorer survival outcomes, suggesting their potential as prognostic markers. In contrast, the expression of TP53, PTEN, and PPP2R1A did not show a significant impact on patient survival. The functional importance of these genes was investigated utilizing pathway enrichment and protein-protein interaction networks. Additionally, pathway enrichment analysis indicated these genes are involved in critical cancer pathways. The findings highlight the importance of integrating epigenetic and transcriptomic data to understand UCEC pathogenesis and suggest that the identified genes could serve as potential biomarkers for early diagnosis and treatment strategies.

Subretinal hemorrhage-induced neurotoxicity is a key cause of vision loss in age-related macular degeneration (AMD). The purpose of this study is to investigate the effects of Propofol on neurotoxicity. Oxygen glucose deprivation (OGD) was used to establish in vitro subretinal hemorrhage model. Gene expression was determined using reverse transcription-quantitative polymerase chain reaction and western blot. Cytokine release was determined using enzyme-linked immunosorbent assay. The interaction between sirtuin 6 (SIRT6) and NLR family pyrin domain containing 3 (NLRP3) was detected using co-immunoprecipitation assay. Cellular function was determined using cell counting kit-8 assay, lactate dehydrogenase assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Propofol suppressed the inflammatory response induced by OGD. Moreover, Propofol inhibited the neurotoxicity and pyroptosis of photoreceptors. Propofol mediated the overexpression of SIRT6, which was downregulated in AMD. Inhibition of SIRT6 alleviated its deacetylation of NLRP3. Additionally, SIRT6 deficiency antagonized the effects of Propofol and promoted the neurotoxicity and pyroptosis of photoreceptors. Taken together, Propofol protects against subretinal hemorrhage-induced neurotoxicity and pyroptosis of photoreceptors via promoting SIRT6-mediated deacetylation of NLRP3.

The complement system (CS) is linked to the progression of gastric cancer (GC), which has a high mortality rate, though its mechanisms in GC remain unclear. This study aims to identify CS-related prognostic genes with causal links to GC, and to investigate their mechanisms. The intersection between differentially expressed genes (DEGs) obtained from the TCGA-STAD dataset and CS-related genes (CRGs) was defined as differentially expressed CRGs (DCRGs). Prognostic genes with a causal association with GC (pCDCRGs) were sequentially identified via Mendelian randomization (MR) analysis and Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, followed by expression analysis. A gene signature and a nomogram were then established based on pCDCRGs and independent prognostic factors. Subsequent analyses focused on functional enrichment, immune relevance, drug sensitivity, gene interactions, and molecular regulatory networks. Eventually, reverse transcription-quantitative PCR (RT-qPCR) was employed to validate expression of pCDCRGs. DCRGs were obtained from the intersection of 8,418 DEGs and 241 CRGs. Among 12 DCRGs with causal association (CDCRGs) with GC, 7 genes were identified as pCDCRGs, including FANCG, FANCF, F2R, C4BPA, SERPINF2, PROC, and CD59. Notably, CD59 was markedly highly expressed in the normal group, whereas the other genes were markedly highly expressed in the GC group. Afterward, an accurate pCDCRG signature was developed. Risk score, age, and stage were recognized as independent risk factors, and the constructed nomogram demonstrated strong predictive accuracy. Additionally, analyses indicated that these 7 pCDCRGs may influence GC by affecting pathways such as complement and coagulation cascades, immune cell infiltration, immune characteristics, immunotherapy responses, and drug sensitivity. These effects may be linked to gene interactions and the regulatory roles of lncRNAs like RMRP and miRNAs such as hsa-mir-613. RT-qPCR showed C4BPA, PROC, F2R, and SERPINF2 were markedly up-regulated, whereas CD59 was markedly down-regulated in GC tissues. This study identified seven complement system-related prognostic genes with causal links to GC, based on which we developed a highly predictive 7-pCDCRG signature, providing valuable insights for clinical prognostic prediction and immunotherapy in GC patients.

Non-small cell lung cancer (NSCLC) has a high global incidence and mortality rate. Although circRNAs have significant attention in tumor research, it's role in NSCLC is uncertain. QRT-PCR and Western blotting were utilized to quantify the expression of circCNKSR2, miR-138-5p, and PLEK2 in NSCLC tissues and cells. The characteristics and subcellular localization of circCNKSR2 were determined using RNase R analysis and qRT-PCR. In vitro functional experiments determined the biological functions of circCNKSR2. The specific binding interactions among circCNKSR2, miR-138-5p, and PLEK2 were evaluated through bioinformatics analysis, luciferase reporter, and rescue assays. In vivo xenograft model was established to examine the impact of circCNKSR2, which was significantly increased in NSCLC tissues and cells. Functional studies demonstrated that silencing circCNKSR2 significantly inhibited NSCLC malignant phenotype and Warburg effect. Bioinformatics analysis and rescue experiments verification indicated circCNKSR2 functioned as a miR-138-5p sponge, and inhibiting miR-138-5p reversed the suppressive effect of silencing circCNKSR2 in NSCLC. Additionally, PLEK2 identified as a miR-138-5p target gene. The potential regulatory role of circCNKSR2 in NSCLC progression and Warburg effect via the miR-138-5p/PLEK2 pathway was demonstrated.

The members of the network (interactome) that controls cancer needs to be known. This network consists of proteins and non-coding, single-stranded RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and transfer RNAs (tRNAs). miRNAs are 21-23 nucleotides-long, and degrade messenger RNAs (mRNAs) and lncRNAs. lncRNAs are longer than 200 nucleotides, and sponge (sequester) miRNAs.

Keloid formation is an undesirable outcome of wound healing and is detrimental to patients' physical and mental health, while the molecular regulators of its pathogenesis, especially non-coding RNAs (ncRNAs), are largely unknown. In this study, we integrated and analyzed RNA-seq and miRNA microarray datasets of skin samples from keloid-prone and healthy normal individuals to detect the dysregulated long ncRNAs (lncRNAs) and miRNAs. We excavated 583 and 104 keloid-specific lncRNAs and miRNAs, respectively. Moreover, the molecular functions of these ln-cRNAs and miRNAs are all related to ossification. Next, we constructed the relationship between lncRNAs and immune cell infiltration, and found the macrophages, NK cells, and dendritic cells were specifically dysregulated in keloid-prone or normal groups during wound healing. We constructed the potential regulatory network between these cell types and 20 dysregulated lncRNAs, suggesting their regulatory function in keloid formation. At last, we constructed the competitive endogenous RNA network and found two hub lncRNAs and five miRNAs, including DLEU1 and SLC25A21-AS1, miR-197-5p, miR-940, miR-6765-5p, miR-711, and miR-4284, which were highly dysregulated during keloid formation. In summary, these results demonstrate that lncRNAs and miRNAs play important roles and form a regulatory network in the pathogenesis, immune infiltration, and development of keloid formation.

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.

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.