Critical Reviews in Eukaryotic Gene Expression最新文献

Uterine corpus endometrial carcinoma (UCEC) is a prevalent malignancy within the female reproductive system, with a rising global incidence. Although thyroid hormone receptor interacting protein 13 (TRIP13) has been implicated in various tumor etiologies and progressions, its role in UCEC remains poorly characterized. This study aimed to delineate TRIP13's expression profile in UCEC by analyzing transcriptome data from multiple databases. We investigated genomic alterations and epigenetic modifications of the TRIP13 gene using the cBioPortal tool. The prognostic value of TRIP13 was assessed via Kaplan-Meier survival analysis and Cox regression modeling. Additionally, we examined TRIP13's impact on immunotherapy responsiveness and chemotherapy sensitivity through immunological and pharmacological analyses. The expression of TRIP13 in both normal endometrial and cancer cell lines was evaluated using quantitative real-time polymerase chain reaction (qPCR). Our findings reveal that TRIP13 expression in UCEC tumor samples is significantly higher than in normal tissues and increases with tumor grade and stage progression. High TRIP13 expression is significantly associated with poor prognosis in UCEC patients, establishing it as an independent prognostic biomarker. TRIP13 shows a positive correlation with immunosuppressive cell infiltration and a negative correlation with immune-activating cell infiltration, suggesting a potential role in tumor immune evasion. Further analysis identified TRIP13 as a potential biomarker for predicting immunotherapy response. Moreover, TRIP13 expression is significantly associated with sensitivity to certain chemotherapeutic agents, indicating its potential as a therapeutic target. qPCR experiments confirmed the overexpression of TRIP13 in endometrial cancer cell lines. The role of TRIP13 in modulating the tumor immune microenvironment, as well as its predictive value for immunotherapy and chemotherapy responses, underscores its importance in developing personalized treatment strategies for UCEC. These findings provide novel molecular targets and therapeutic insights for a precision medicine approach to UCEC.

Methyltransferase-like 14 (METTL14) has been identified as a protective factor in central nervous system disorders, yet its involvement in Parkinson's disease (PD) remains underexplored. This study aimed to investigate the role of METTL14 in PD. An in vitro PD model was established by exposing neurons to 1-methyl-4-phenylpyridinium (MPP+). mRNA levels were quantified via real-time-quantitative PCR. Protein expression was assessed through Western blot. The release of pyroptosis-related cytokines was detected using enzyme-linked immunosorbent assay. N6-methyladenosine (m6A) levels were measured using an m6A assay. m6A enrichment was pinpointed with a methylated RNA immunoprecipitation assay. The transcriptional activity of nuclear factor, erythroid 2 (NFE2) was evaluated using a luciferase assay. Cell viability, neuronal cytotoxicity, and neuronal death were respectively determined using Cell Counting Kit-8, lactate dehydrogenase, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Our findings unveiled that METTL14 expression is diminished following MPP+ exposure, which in turn triggers neuroinflammation and pyroptosis. Conversely, overexpression of METTL14 mitigates neuroinflammation and pyroptosis, and restores neuronal function. Mechanistically, METTL14 augments the m6A modification of NFE2 at a specific site, thereby preserving its mRNA stability. However, NFE2 knockdown exacerbates neuroinflammation and pyroptosis. In summary, METTL14 safeguards against neurodegeneration in PD by modulating the m6A modification of NFE2, positioning the METTL14/NFE2 axis as a potential therapeutic target for PD.

Myocardial fibrosis is a critical pathological process in the progression of heart failure and other cardiovascular diseases. Kaempferol (KMP), a natural flavonoid, has antioxidant and anti-inflammatory properties. This study investigates the effects of KMP on myocardial fibrosis. Isoproterenol injection was used to establish myocardial fibrosis mouse model. Cardiac function was assessed by echocardiography. Histology analysis was conducted using Masson assay and Sirius red staining. The expression of survival of motor neuron 1 (α-SMA) and Collagen III was detected using immunohistochemistry. RNA expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cytokine release was detected using enzyme-linked immunosorbent assay. Protein expression was detected using Western blot. We found that KMP treatment improved cardiac function as well as suppressed myocardial fibrosis. Moreover, KMP treatment decreased expression of fibrosis-related genes and attenuated inflammation in fibrotic hearts. Furthermore, KMP treatment inhibited the expression of coagulation factor VII (FVII), the overexpression of which promoted inflammation response and myocardial fibrosis. In summary, KMP exerts protective effects against myocardial fibrosis via downregulating FVII. These findings suggest that KMP may be a promising therapeutic candidate for myocardial fibrosis.

Asthma represents a chronic disorder with aberrant immunological and inflammatory responses. We analyzed the levels and clinical significance of serum markers serum amyloid A (SAA) and immunoglobulin M (IgM) in Mycoplasma pneumoniae (MP)-infected children with asthma. MP-infected children were allocated into the Asthma (n = 64) and N-Asthma (n = 104) groups, with baseline information collected. Levels of IgE, c-reactive protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, interleukin-4/interferon-γ (IL-4/IFN-γ), transforming growth factor β1 (TGF-β1), SAA and IgM were determined by ELISA. Tidal breathing lung function [inspiratory time (TI), expiratory time (TE), inspiratory volume (V-TI), expiratory volume (V-TE), tidal volume (VT) and respiratory rate (RR)] was assessed using a pulmonary function instrument. The relationship of serum SAA and IgM with IgE, IL-4/IFN-γ, TGF-β1, and tidal breathing lung function in MP-infected asthmatic children, and their diagnostic value for asthma occurrence in MP-infected children were analyzed by Spearman analysis and receiver operating characteristic curve. IgE, V-TI, V-TE, VT, IL-4/IFN-γ, TGF-β1, SAA and IgM indexes in MP-infected asthmatic children surpassed those without asthma. Serum SAA and IgM significantly positively correlated with IgE, IL-4/IFN-γ, TGF-β1, V-TI, V-TE and VT, which had certain diagnostic value for asthma in MP-infected children. The incidence of asthma was higher in MP-infected children with high SAA and IgM expression levels. The diagnostic efficacy of SAA and IgM combined test surpassed single detection. Serum SAA and IgM were highly expressed in MP-infected asthmatic children, and their combined detection had high diagnostic value for asthma in MP-infected children.

Prostate cancer (PRAD) progression varies significantly among patients, with metabolic reprogramming linked to oncogenesis and immune response. However, the prognostic and immune-related roles of metabolic reprogramming-related genes (MRGs) in PRAD remain unclear. PRAD transcriptomic, mutation, and clinical data from TCGA were analyzed. WGCNA identified PRAD-associated gene modules. NMF clustering stratified patients into two molecular subgroups. Prognostic MRGs were screened via univariate Cox and LASSO regression. A gene-based prognostic model was established and validated using ROC, PCA, and Kaplan-Meier analyses. A clinical-variable nomogram predicted survival, with external validation via GEO data set GSE70770. Immune traits of subtypes/risk groups were assessed via ESTIMATE, CIBERSORT, and ssGSEA. Drug sensitivity and gene expression (qRT-PCR) were evaluated. Two metabolic subtypes with distinct survival and immune patterns were identified. A four-gene signature (AKR1C2, PITPNM3, PLA2G5, UCK2) formed a prognostic model. Risk stratification revealed groups with divergent survival rates. High-risk patients exhibited poorer outcomes, reduced immune infiltration, and altered drug sensitivity. The MRG prognostic model stratifies PRAD patients by survival and immune landscape, aiding precision immunotherapy and drug discovery.

Never in mitosis a related kinases 6 (NEK6) is a serine/threonine kinase, and dysregulation of NEK6 is associated with malignant progression of human cancers. Nonetheless, the biological function and molecular mechanism of NEK6 in hepatocellular carcinoma (HCC) are unknown. Our study found that NEK6 was obviously raised in HCC patient tissues and cells, and patients with high NEK6 expression had a worse prognosis. Silencing of NEK6 reduced the growth, metastasis, cell cycle, and glycolysis of HCC cells while facilitating apoptosis. In vivo experiments also showed that NEK6 knockdown dramatically hampered tumor growth, suggesting that NEK6 enhanced HCC progression in vivo and in vitro. Next, we proved that TCP10L was a target gene of NEK6, and NEK6 negatively regulated TCP10L expression. Mechanistically, we confirmed that NEK6 was bound to TCP10L, and NEK6 degraded TCP10L protein expression through ubiquitination. Rescue experiments also declared that TCP10L reversed the effect of NEK6 on HCC cells. Our results disclosed that NEK6 heightened HCC progression and glycolysis through ubiquitination of TCP10L. Our study may provide a new perspective for the treatment of HCC.

Gastric cancer (GC) is a highly prevalent malignancy with significant morbidity and mortality rates. N4-acetylcytidine (ac4C), an emerging RNA modification, has been implicated in tumorigenesis of GC. NAT10, an enzyme responsible for ac4C modification, has garnered attention for its potential role in cancer progression. This study investigates the role of NAT10 in GC. We analyzed NAT10 expression in GC tissues and cell lines using Rt-qPCR, immunohistochemistry and Western blotting. Functional studies were conducted using shRNA and overexpression models in vitro and in vivo. The molecular mechanisms underlying NAT10-mediated GRB7 regulation were elucidated through ac4C modification assays. Our findings revealed that NAT10 is overexpressed in GC tissues and cells and predicted poor prognosis of GC patients. Inhibition of NAT10 suppressed the proliferation, migration, and invasion of GC cells. Mechanistically, NAT10-mediated ac4C modification enhanced expression of GRB7 by promoting its mRNA stability. Overexpression of GRB7 antagonized the effects of NAT10 shRNA and promoted the malignant behaviors of GC. In vivo studies showed that NAT10 knockdown reduced tumor growth. Collectively, our study highlights the crucial roles of NAT10 and ac4C modification in GC progression through the regulation of GRB7. Therefore, targeting NAT10/GRB7 axis may be a novel strategy for GC.

Cell division, the fundamental mechanism of reproduction, is the basis of life. In highly evolved organisms, particularly in humans exposed to abnormal chronical endogen and exogen stress-factors, uncontrolled cell division can occur. Consideration of the space-wise uncontrolled cell division and an increased level of human chorionic gonadotropin (hCG) as the decisive initial abnormalities of cancer has induced this study. A correlation between these two abnormalities could not be excluded. Cell division, namely cell division of eukaryotic cells, is subject of numerous publications. Interestingly, the decisive agonist that activates and governs this most important and most complex biological process is unknown. So, it is also unknown whether hCG in its organism specific form is only one among a multitude of known promotors, or if it is possibly even the decisive agonist of controlled and uncontrolled cell division. A higher-than-normal hCG level might overrule healthy cells' growth control. Identification of the decisive agonist of controlled and uncontrolled cell division appeared of fundamental importance and became the main object of this paper. To evaluate the potential of hCG as the decisive agonist of cell division, hCG's first and most important accomplishments for the genesis of a human life were analyzed. Combinations and deductions of interconnected facts expose a higher-than-normal hCG level via the nuclear super receptor family as the decisive agonist of the first cell division of the first human cell, the zygote, and by consanguinity for the cell divisions of its daughter cells, including cancer cells.

The uridine diphosphate-glycosyltransferase (UGT) family catalyses the glucuronidation of the glycosyl group of a nucleotide sugar to an acceptor compound (substrate), it serves as controlling reaction for bioactivity, storage and decrease toxicity of different compounds in living organisms. UGT71B8 belongs to 71B family of UGTs and its donor sugars are UDP glucose, UDP galactose and UDP 5S glucose, respectively. The current study was designed to induce site-directed mutagenesis (SDM) to investigate the activity in UGT71B8 enzyme. During first step, in silico conformational change through 3D structure model was drawn and it was found that all the amino acids of mutation site were found in allowed region. The relative surface accessibility (RSA) and absolute surface accessibility (ASA) of UGT71B8 were found as 0.042-0.037 and 7.424, respectively, which shows that UGT71B8 T138M remains stable after SDM. This prediction model thus led to the efficacious mutation of UGT71B8 enzyme. Mass spectrometric analysis of UGT71B8T138M showed reduced activity with its substrate UDP glucose and kaempherol as acceptor molecule. Moreover, no new substrate activity of UGT71B8 was found. This data would direct future endeavors to engineer more glycosyltransferases of plants to augment its activity with different substrates and provide a basis for more exploration of UGT71B8 as an active compound for potential anti-cancer therapeutics.

Long non-coding RNAs (lncRNAs) are intensively involved in the pathogenesis of multiple myeloma (MM). The purpose of this study was to investigate the potentials of DUBR in MM. Gene expression was determined using RT-qPCR and western blot. The release of ROS, MDA, ferrous iron, and GSH was detected with corresponding assays. Cell behavior was detected using CCK-8, colony formation, transwell, and PI staining assays. The binding sites between miR-17-3p and DUBR/TFRC was verified firmed by RIP, RNA pull-down, as well as luciferase assays. We found that low levels of DUBR predicted poor prognosis of MM patients. However, overexpressed DUBR enhanced the chemosensitivity of MM cells to bortezomib (BTZ), as well as promoted the ferroptosis of MM cells. DUBR sponged miR-17-3p to upregulate TFRC. However, TFRC knockdown abrogated the effects of overexpressed DUBR and promoted the aggressiveness of MM cells. In summary, DUBR promotes the chemosensitivity of MM cells to BTZ via regulating miR-17-3p/TFRC axis. Therefore, targeting DUBR may be a potential target for MM.