Biochemical Genetics最新文献

Squamous cell carcinoma of the lips and oral cavity (OSCC) contributes to 90% of the nonmelanocytic tumors of these anatomical regions. Liquid biopsy is a new, relatively noninvasive, and effective method for screening, diagnosing, and classifying tumors. Considering the role of integrin β8 subunit (ITGB8) and Myocardial infarction-associated transcript (MIAT) lncRNA in the pathogenesis and progression of different types of cancer, we aimed to evaluate the probable differences in the level of expression of these two biomarkers in control and OSCC cases and evaluate their diagnostic potential as a biomarker in tissue and liquid samples (blood and saliva) biopsy. Tissue, blood, and saliva samples from 60 participants (30 in each study group) were obtained for precise evaluation. Using extracted RNA from the samples and PCR assay, the expression level of these biomarkers was measured in control and case group samples. Parametric and nonparametric tests were equipped for the evaluation of the results. ROC analysis was done to determine the diagnostic potential of these biomarkers. Our results claimed significant differences in the level of expression of ITGB8 and MIAT-lncRNA among our study cohorts' samples. The ROC analysis revealed the valuable potential of these factors in the diagnosis of disease in tissue and blood samples. The results of the analysis for the saliva samples suggest a satisfactory diagnostic value for ITGB8 but nonsignificant diagnostic value for the MIAT-lncRNA. ITGB8 and MIAT-lncRNA expression levels could be considered in the evaluation of suspicious oral cavity lesions, especially in the tissue and blood samples.

Myocardial ischemia-reperfusion injury (MIRI) is a major clinical challenge, marked by metabolic disruptions and cellular damage following the restoration of blood flow after ischemia. During ischemia, the heart shifts from fatty acid metabolism to glucose metabolism, leading to metabolic abnormalities, including reduced intracellular pH, ion disturbances, cell swelling, and apoptosis. Upon reperfusion, fatty acid β-oxidation resumes, becoming the dominant energy source, which induces excessive oxidative stress and aggravates myocardial injury. To explore the role of FTO (Fat mass and obesity-associated protein) in m6A demethylation of MZF1 and its regulation of DECR1, a key enzyme involved in fatty acid β-oxidation, in the context of MIRI. We investigated the molecular mechanisms by which FTO-mediated m6A modification of MZF1 regulates DECR1 expression, leading to enhanced fatty acid oxidation during reperfusion and its contribution to the exacerbation of MIRI. Our findings suggest that FTO-mediated demethylation of MZF1 promotes the expression of DECR1, thereby enhancing fatty acid oxidation. This process intensifies oxidative stress and worsens myocardial injury during ischemia/reperfusion. The FTO-mediated m6A modification of MZF1 represents a critical mechanism in the regulation of fatty acid oxidation and the exacerbation of MIRI. These insights offer potential therapeutic targets to mitigate the harmful effects of reperfusion injury in myocardial infarction.

Background: Lung cancer is a malignant tumor of the bronchial mucosa or gland, the morbidity and mortality increase rapidly, and it is a great threat to human health and life. Propofol is a short-acting intravenous anesthetic, and its effect on lung cancer has been studied, but the mechanism is not thorough.

Methods: The 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and transwell assays were applied to assess the viability, proliferation, apoptosis, and invasion, respectively. The glycolytic analysis was performed using the corresponding kits. The gene expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. The interaction between genes was obtained from the STRING database or ubiquitination analysis. The xenograft tumor mouse models were established to verify the effects of propofol in vivo, and IHC was adopted to detect the gene expression in vivo.

Results: In this study, we found that propofol impeded lung cancer progression and glycolysis. Additionally, propofol curbed the triosephosphate isomerase 1 (TPI1) protein and increased TPI1 ubiquitination modification, meanwhile, propofol exerted inhibitory functions in lung cancer through TPI1. Besides, the protein stability and ubiquitination modification of TPI1 were mediated by ubiquitin-specific peptidase 5 (USP5), and USP5 expedited the progression and glycolysis of lung cancer via TPI1. In the meantime, propofol modulated USP5-regulated functions in lung cancer. In vivo, propofol-inhibited tumor growth by regulating USP5-mediated TPI1.

Conclusion: This study presents propofol/USP5/TPI1 curbing glycolysis metabolism and tumor growth in lung cancer, indicating that propofol-mediated ubiquitination of the target gene may be a new therapeutic target for lung cancer.

We observed the expression of long non-coding RNA (lncRNA) MALAT1 and microRNA (miR)-17-5p in patients with diabetic lower extremity atherosclerosis (LEAD) and EA. hy926 human endothelial cells (EA. Hy926 cells). We further investigated whether knockdown of MALAT1 (sh-MALAT1) could protect endothelial cells and improve the occurrence of atherosclerosis through miR-17-5p, aiming to dissect the underlying mechanism. Patients with type 2 diabetes were stratified into two groups: those with lower extremity atherosclerotic lesions (LEAD group) and those without (T2DM group). For in vitro studies, EA. hy926 cell cultures were treated with high glucose concentrations and transfected. The mRNA expression levels of MALAT1 and miR-17-5p were accessed. The relationship between molecules was verified by double luciferase assay. Biological function was evaluated using lactate dehydrogenase (LDH) assay, Hoechst 33342/propidium iodide (PI) fluorescence staining, and Western blotting. MALAT1 was highly expressed and miR-17-5p was lowly expressed in both peripheral blood samples from LEAD patients and high glucose-cultured endothelial cells. Knockdown of MALAT1 (sh-MALAT1) or miR-17-5p mimic attenuated the release of LDH, the levels of pyroptosis-associated protein, and the number of PI-positive cells in high glucose-treated endothelial cells, while the miR-17-5p inhibitors had the opposite effect. The dual-luciferase assay determined that miR-17-5p is a downstream target of MALAT1. Finally, co-transfection with sh-MALAT1 and miR-17-5p inhibitors attenuated the protective effect of silenced MALAT1 on high glucose-mediated endothelial cell pyroptosis. MALAT1 may play an essential role in high glucose-induced endothelial cell pyroptosis by regulating miR-17-5p.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and neuronal loss. Ferroptosis, a form of regulated cell death driven by iron overload and lipid peroxidation, has been implicated in AD pathology. DiHuangYinZi (DHYZ), a traditional Chinese herbal remedy, has been suggested to ameliorate cognitive impairments and reduce ferroptosis in AD models. This study aimed to investigate the effects of DHYZ on learning, memory, ferroptosis markers, and neuronal integrity in APP/PS1 transgenic mice. Six-month-old APP/PS1 transgenic mice were treated with DHYZ or donepezil for four weeks. Learning and memory functions were evaluated using the Morris Water Maze (MWM) and open field test. Neuronal integrity was assessed through Hematoxylin and Eosin (H&E) and Nissl staining. Ferroptosis markers, including superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and the GSH/GSSG ratio, were measured in hippocampal tissues. Ferroptosis-related protein expressions, such as ferritin, DMT1, FPN1, Nrf2, and GPX4, were analyzed using Western blot. DHYZ treatment significantly improved learning and memory deficits in APP/PS1 mice, as evidenced by reduced escape latency and increased platform crossings in the MWM. DHYZ also reversed anxiety-like behavior in the open field test. Histological analysis showed that DHYZ treatment restored neuronal integrity, as indicated by better cellular arrangement and staining compared to untreated APP/PS1 mice. DHYZ inhibited ferroptosis by reducing iron overload, increasing SOD and GSH levels, and normalizing the GSH/GSSG ratio. Moreover, DHYZ modulated the expression of ferroptosis-related proteins, restoring FPN1 levels while reducing ferritin and DMT1 expressions. Nrf2 and GPX4 levels, which were reduced in APP/PS1 mice, were significantly increased after DHYZ treatment. DHYZ effectively improved cognitive deficits, inhibited ferroptosis, and restored neuronal integrity in APP/PS1 mice. These findings suggest that DHYZ may have therapeutic potential for AD by targeting ferroptosis and regulating iron metabolism.

The chloroplast (cp) genome of the tree fern Cyathea delgadii Pohl ex Sternb. was assembled and annotated to investigate its structure and evolution within the Cyatheales order. The genome, sequenced using Oxford Nanopore Technologies, has a total size of 165,248 bp, comprising a large single-copy (LSC) region of 94,738 bp, a small single-copy (SSC) region of 22,012 bp, and two inverted repeat (IR) regions of 24,251 bp each. It contains 89 protein-coding genes, eight rRNAs, and 33 tRNAs. Comparative phylogenomic analyses involving 19 species of Cyatheales have revealed that the cp genome of C. delgadii shares similarities in gene content with other ferns of the Cyatheaceae family; however, it demonstrates variations in both genome size and GC content. Variations in cp genome size were observed across the Cyatheales species, ranging from 154,046 bp in Gymnosphaera denticulata (Baker) Copel to 168,244 bp in Dicksonia squarrosa (G.Forst) SW. Gene content analysis showed that most species have a conserved number of protein-coding genes, rRNAs, and tRNAs, suggesting structural stability. However, Cibotium spp. has a reduced number of protein-coding genes (87), possibly due to gene loss or transfer to the nuclear genome. Phylogenetic analyses using both whole genome and SNP data showed comparable clustering among Alsophila and Gymnosphaera species, while C. delgadii occupied a basal to intermediate position. The overall guanine-cytosine (GC) content of C. delgadii was calculated to be 40.95%, with a significantly higher content of 44.03% observed in the intragenic regions. An analysis of codon usage bias indicated a preference for codons ending with adenine or thymine, which aligns with the genome's adenine-thymine (AT) richness. This study provides valuable genomic resources and insights into the evolution of Cyatheales cp genomes, emphasizing both conserved features and specific adaptations within this group of ferns.

Glioblastoma is the most aggressive and malignant tumor of the central nervous system. Current treatment options, including surgical excision, radiotherapy, and chemotherapy, have Limited efficacy, with a median survival rate of approximately 15 months. To develop novel therapeutics, it is crucial to understand the underlying molecular mechanisms driving glioblastoma. However, obtaining healthy tissue counterparts for comparison is often challenging due to the critical nature of the tissues and the tumor's location. This study aimed to compare the transcriptomic profiles of glioblastoma tissues with those of adjacent healthy tissues, to elucidate key pathways and identify upstream regulators involved in glioblastoma pathogenesis. Twenty-six pairs of glioblastoma tissues and their adjacent healthy tissues were obtained during surgery. The tumor and healthy origins were confirmed through histopathological examination. Twelve pairs were analyzed via transcriptome analysis by using the Ion GeneStudio S5 system. Ingenuity pathway analysis was performed to identify the associated pathways and upstream regulators. Selected 51 upstream regulators were analyzed using qRT-PCR. Three pairs were excluded from the RNA-sequencing (RNA-seq) analysis due to similarities between normal and tumor tissues. The dysregulated pathways were primarily associated with neuronal connections and neurotransmitter pathways. The expression patterns of upstream regulators were consistent with RNA-seq results. Molecular changes linked to the initiation of tumors can begin at an early stage, potentially preceding the appearance of clinical symptoms. The dysregulated pathways were particularly associated with specific brain tissue types. The expression of upstream regulators was consistent across both methods; however, their functional roles need further investigation.

To evaluate the expression of hsa_circ_0077007 in the serum of colorectal cancer (CRC) patients and offer a foundational theory for the prognosis of CRC. The present study focuses on investigating the biological function and therapeutic target of hsa_circ_0077007 in colorectal cancer CRC. Retrieve the GEO database and use the GEO2R tool to analyze the GSE dataset (GSE223001 and GSE159669) to obtain aberrantly expressed circRNAs. Serum hsa_circ_0077007 expression was measured by qRT-PCR in 107 CRC patients. Kaplan-Meier curve was used to analyze the repercussions of hsa_circ_0077007 expression on overall survival and prognosis. After the knockout of hsa_circ_0077007, the biological cellular functions of CRC were characterized. Finally, the downstream molecular expression mechanism of hsa_circ_0077007 was further explored. Hsa_circ_0077007 was among the abnormal circRNAs in GSE223001 and GSE159669. Compared to normal controls, CRC patients exhibited elevated levels of hsa_circ_0077007 expression in their serum. Additionally, the expression levels of hsa_circ_0077007 were significantly increased across four distinct CRC cellular lines, especially SW620 and LoVo cellular lines. Furthermore, high levels of hsa_circ_0077007 expression were associated with a reduced overall survival rate. In vitro, loss-of-function assays for hsa_circ_0077007 resulted in a marked reduction in cell proliferation, invasion, and migration, accompanied by a boost in cell apoptosis. Hsa_circ_0077007 can sponge miR-383-5p, and then inhibit the expression of miR-383-5p. High expression of hsa_circ_0077007 is indicative of shorter survival rates among CRC patients. The hsa_circ_0077007 has been demonstrated to enhance cellular proliferation, invasion, and migration, while concurrently inhibiting apoptosis.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths globally. Enhancer of zeste homolog 2 (EZH2), a methyl-transferase and master transcriptional regulator frequently overexpresses in a variety of malignancies. Long non-coding RNAs (lncRNAs) play a significant role in regulating gene expression and are intricately involved in the EZH2 oncogenic regulatory network. We aimed in this study to investigate the expression of EZH2-associated lncRNAs and their probable regulatory role in GC progression. RNA-seq and miRNA-seq data from 375 tumor and 32 normal samples were retrieved from the TCGA database. Differential expression and correlation analyses were performed to identify EZH2-associated lncRNAs. A competing endogenous RNA (ceRNA) network comprising lncRNAs, miRNAs, and mRNAs was constructed and visualized. Functional genomics analysis including EZH2 knockdown and induced overexpression experiments were carried out in AGS and MKN-45 GC cell lines to validate the expression of selected lncRNAs using RT-qPCR. EZH2-correlated analysis revealed 16 upregulated and 8 downregulated lncRNAs with significant associations. EZH2 expression modulation studies confirmed that expression levels of lncRNAs including PVT1, MNX1-AS1, AC103702.2, PCAT7, LINC01235, LINC02086, MIR99AHG, and MAGI2-AS3 were regulated by EZH2 in GC cells. EZH2 modulates the expression of several key lncRNAs associated with gastric cancer progression, suggesting that the EZH2/lncRNA axis could serve as a potential therapeutic target. Targeting this axis may open new avenues for influencing critical molecular pathways involved in GC development.