Critical Reviews in Eukaryotic Gene Expression最新文献

With the increasing aging population in China, the incidence rate of knee osteoarthritis is expected to rise annually. Therefore, we conducted a study to investigate the crucial role of LPCAT3 in osteoarthritis and its underlying mechanisms. We collected samples from normal volunteers (n = 12) and patients with osteoarthritis (n = 12) at our hospital. It was observed that LPCAT3 mRNA expression was reduced and positively correlated with IL-1β mRNA expression in patients with osteoarthritis. In a mouse model, LPCAT3 mRNA and protein expression were found to be suppressed. Furthermore, in an in vitro model, the enrichment level of LPCAT3 mRNA was inhibited by a specific m6A antibody through si-METTL3. Si-METTL3 also reduced the stability of LPCAT3 mRNA in the in vitro model. The inhibition of LPCAT3 was found to exacerbate osteoarthritis in the mouse model. Additionally, LPCAT3 was shown to reduce inflammation in the in vitro model. It was also observed that LPCAT3 reduced chondrocyte ferroptosis by inhibiting mitochondrial damage. LPCAT3 protein was found to interact with ACSL4 protein, and its up-regulation suppressed ACSL4 expression in the in vitro model. ACSL4 was identified as a target of LPCAT3 for suppressing mitochondrial damage in the in vitro model. In conclusion, this study demonstrates that LPCAT3 improves osteoarthritis by regulating ACSL4 to inhibit chondrocyte ferroptosis, thus providing a novel target for the treatment of osteoarthritis.

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.

Bladder cancer (BC) is the second most common genitourinary malignancy. Long noncoding RNA (lncRNA) is implicated in BC progression. This study delved into the underlying mechanism of lncRNA MEG3 in BC. Bioinformatics analysis predicted the expression of lncRNA MEG3, its association with the survival of BC patients, its subcellular localization, and its binding sites with miR-21-5p. Differentially expressed genes (DEGs) in the GSE13507 chip were analyzed using GEOexplorer, downstream targets of miR-21-5p were predicted from databases, and the overlapping genes were analyzed by the website Venny2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html); their impacts on patient survival were analyzed by the Starbase database. The expression of SPRY2 and TGFBI associated with patient survival was analyzed in TCGA. RT-qPCR and western blot were performed to detect levels of MEG3, miR-21-5p, and SPRY2 in BC/SV-HUC-1 cells. Malignant biological behaviors of BC cells were detected using CCK8, flow cytometry, and Transwell assays. RNA pull-down and dual-luciferase assays were employed to verify the binding relationship of miR-21-5p with MEG3 and SPRY2. MEG3 was found to be lowly expressed in BC cells and mainly distributed in the cytoplasm. Over-expression of MEG3 was found to inhibit BC cell activity, promote apoptosis, and reduce invasion and migration. miR-21-5p was found to be highly expressed in BC cells, and its down-regulation was found to inhibit the malignant behavior of BC cells. Over-expression of miR-21-5p was found to reverse the effect of pcDNA3.1-MEG3 on BC cells. MEG3 was found to competitively bind to miR-21-5p as a ceRNA to promote SPRY2 levels. LncRNA MEG3 promotes SPRY2 expression by competitively binding to miR-21-5p, thereby inhibiting proliferation and promoting apoptosis of BC cells.

H subunit of V-ATPase (ATP6V1H) is specifically expressed in osteoclasts and its deficiency lead to osteoporosis. Our group previously found four intronic SNPs of ATP6V1H related to reduced bone mineral density, but the mechanisms was not clear. In this study, we found that the above four SNPs were located at lncRNA lnc-TCEA1-3 by using bioinformatics analysis. We further detected the function of lnc-TCEA1-3 on regulating ATP6V1H and osteoclast function using Atp6v1h knockout mice, lentivirus transfection and qPCR analysis. Over expression of lnc-TCEA1-3 up regulated the expression of ATP6V1H in HEK293 cells, HOS cells and primarily cultured osteoclasts, and increased the number of primarily cultured osteoclasts. In addition, over expression of lnc-TCEA1-3 exerted distinct effect on two transcripts of ATP6V1H in HEK293, HOS and osteoclasts. This study will facilitate the in-depth analysis of the effects of ATP6V1H on bone diseases, and discover new therapeutic strategies.

Long non-coding RNA (lncRNA)-mediated control of gene expression contributes to regulation of biological processes that include proliferation and phenotype, as well as compromised expression of genes that are functionally linked to cancer initiation and tumor progression. lncRNAs have emerged as novel targets and biomarkers in breast cancer. We have shown that mitotically associated lncRNA MANCR is expressed in triple-negative breast cancer (TNBC) cells and that it serves a critical role in promoting genome stability and survival in aggressive breast cancer cells. Using an siRNA strategy, we selectively depleted BRD2, BRD3, and BRD4, singly and in combination, to establish which bromodomain proteins regulate MANCR expression in TNBC cells. Our findings were confirmed by using in situ hybridization combined with immunofluorescence analysis that revealed BRD4, either alone or with BRD2 and BRD3, can support MANCR regulation of TNBC cells. Here we provide evidence for MANCR-responsive epigenetic control of super enhancers by histone modifications that are required for gene transcription to support cell survival and expression of the epithelial tumor phenotype in triple negative breast cancer cells.

The enhanced uptake of glucose by cancer cells via aerobic glycolysis occurs when the lactic acid pathway is favored over the citric acid cycle. The lactic acid cycle in cancer cells influences the cytosolic concentration of metabolic fluorophores including NADH (the reduced form of nicotinamide adenine dinucleotide) and flavin adenine dinucleotide (FAD). In particular, the literature has shown that breast cancer influences the relative magnitude of fluorescence from NADH and FAD. A multispectral imaging system has been developed for rapid non-destructive imaging of intrinsic fluorescence in tissue. This paper compares in vivo data to fresh ex vivo data gathered as a function of time in mouse models. The data indicate that, if measured within 30 min of excision, a cancer diagnosis in fresh ex vivo tissue correlates with a cancer diagnosis in in vivo tissue. These results justify a plan to evaluate fresh ex vivo human tissue to quantify the sensitivity and specificity of the multispectral system.

Cervical cancer is a common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) are frequently involved in the pathogenesis of cervical cancer. Therefore, the present study aimed to investigate the potentials of lncRNA799 in cervical cancer. mRNA and protein expression were detected by reverse transcription-quantitative polymerase chain reaction and Western blot analysis, respectively. Cellular functions were assessed using CCK-8, wound healing and transwell analysis. The binding potential of zinc finger E-box-binding homeobox 1 (ZEB1) on the promoter of lncRNA799 was predicted utilizing the JASPAR database, and was then verified by luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, the gene interactions were assessed using RNA immunoprecipitation and co-immunoprecipitation assays. The results demonstrated that lncRNA799 was upregulated in cervical cancer cells. However, lncRNA799 deficiency suppressed the proliferation and epithelial-mesenchymal transition of cervical cancer cells. Furthermore, lncRNA799 could interact with eukaryotic translation initiation factor 4A3 to maintain the mRNA stability of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) and promote the interaction between ZEB1 and TBL1XR1. Additionally, the results showed that ZEB1 could transcriptionally activate lncRNA799. Taken together, the present study suggested that the lncRNA799/TBL1XR1/ZEB1 axis could form a positive feedback loop in cervical cancer and could be, therefore, considered as a potential therapeutic strategy for cervical cancer.

The objective of this study is to assess the prevalence of antibiotic-resistant genes (ARGs) in the intestines of infants and the factors affecting their distribution. Breast milk and infant stool samples were collected from nine full-term, healthy mother-infant pairs. The bacterial distribution and various types of ARGs present in the samples were analyzed using metagenomic next-generation sequencing. Over a period spanning from 2 to 240 d after birth, a total of 273 types of ARGs were identified in both infant feces and breast milk, exhibiting a trend of increasing prevalence over time. High concentrations of representative ARG populations were identified in the intestines of infants, especially at 12-15 d after birth. These populations included APH3-Ib, tetW/N/W, mphA, and Haemophilus influenzae PBP3, and multiple ARG Escherichia coli soxS that were resistant to common clinically used aminoglycoside, tetracycline, macrolide, and beta-lactam antibiotics. Gammaproteobacteria and Bacilli, especially Enterococcus, Staphylococcus, Acinetobacter, Streptococcus, and Escherichia were among the identified ARG carriers. Maternal age and body mass index (present and before pregnancy), infant sex, maternal consumption of probiotic yogurt during pregnancy, and lactation might be substantial factors influencing the occurrence of ARG-carrying bacteria and ARG distribution in the infant feces. These results indicate that environmental factors may influence the distribution of ARG-carrying bacteria and ARGs themselves in infants during early life. Providing appropriate recommendations regarding maternal age, body mass index during pregnancy, and use of probiotic products could potentially mitigate the transmission of antibiotic-resistant microbiota and ARGs, thereby diminishing the risk of antibiotic-resistant infections and safeguarding children's health.

Neuroblastoma is a malignant tumor of neuroblasts, immature nerve cells found in several areas of the body. It usually affects children under age of 5. As usual, the tumor has ability to grow rapidly and to expand vastly which ultimately leads to death. Mostly, management decisions can be drawn by the prediction of the stage of the disease as well as age at the time of its diagnosis. There are four main stages of neuroblastoma, and treatment is according to the low and high risk of the disease. Several cytotoxic agents along with other therapies (antibody therapy, gene therapy, and even immunological therapies, antiangiogenic therapy, etc.) are used. Immunotherapy also has an important treatment option used nowadays for neuroblastoma. The discovery of major neuroblastoma-predisposition gene anaplastic lymphoma kinase cause somatic transformation or gene strengthening in diagnosed neuroblastoma. Promising new antiangiogenic strategies have also been introduced for the treatment of neuroblastoma with multiple mylomas. To manage numerous myelomas and cancers, including neuroblastoma, bone marrow transplantation and peripheral blood stem cell transplantation may be used.

Gestational diabetes mellitus (GDM) complicated with preeclampsia can lead to polyhydramnios, ketosis. Herein, we explored that CPEB4 in cancer progression of preeclampsia and its underlying mechanism. All the serum samples were collected from patients with preeclampsia. These was the induction of CPEB4 in patients with preeclampsia. The serum of CPEB4 mRNA expression was positive correlation with Proteinuria, systolic blood pressure and diastolic blood pressure in patients. The serum of CPEB4 mRNA expression was also negative correlation with body weight of infant in patients. The serum of CPEB4 mRNA expression also was negative correlation with GPX4 level and GSH activity level in patients. The serum of CPEB4 mRNA expression was positive correlation with iron content in patients. CPEB4 gene inhibited trophoblast cell proliferation. CPEB4 gene promoted trophoblast cell ferroptosis by mitochondrial damage. CPEB4 gene induced PFKFB3 expression by the inhibition of PFKFB3 Ubiquitination. PFKFB3 inhibitor reduced the effects of CPEB4 on cell proliferation and ferroptosis of trophoblast cell. Taken together, the CPEB4 promoted trophoblast cell ferroptosis through mitochondrial damage by the induction of PFKFB3 expression, CPEB4 as an represents a potential therapeutic strategy for the treatment of preeclampsia or various types of GDM.