International Journal of Genomics最新文献

Aberrant patterns of 5-methylcytosine (m5C)-based ribonucleic acid (RNA) methylation have critical roles in various human diseases, but their importance in spinal cord injury (SCI) is largely unknown. We explore the expression patterns and potential roles of m5C-based regulators of RNA modification after SCI. We analyzed 16 m5C-based regulators of RNA modification in tissues with SCI and normal rats from the Gene Expression Omnibus database. We constructed a "gene signature" of m5C-based regulators of RNA modification to predict the prognosis of SCI using least absolute shrinkage and selection operator regression and random-forest strategy. We found that the m5C-related genes, deoxyribonucleic acid (DNA) methyltransferase1 (Dnmt1), methyl-CpG binding domain protein 2 (Mbd2), ubiquitin-like with PHD and ring finger domains 1 (Uhrf1), uracil-N-glycosylase (Ung), and zinc finger and BTB(brica-brac, tramtrack, and broad) domain containing 38 (Zbtb38) had high expression, and zinc finger and BTB domain containing 4 (Zbtb4) had low expression in SCI. Analysis of the correlation between the gene sets of m5C-based regulators of RNA modification and immune-cell infiltration and immune response revealed Dnmt1, DNA methyltransferases 3A (Dnmt3a), Mbd2, and Ung to be positive regulators of the immune microenvironment, and Zbtb4 may negatively regulate the immune environment. Then, two molecular subtypes were identified based on 16 m5C-regulated genes. Functional-enrichment analysis of differentially expressed genes between different patterns of m5C-based modification was undertaken. Through the creation of a protein-protein interaction network, we screened 11 hub genes. We demonstrated their importance between SCI group and sham group using real-time reverse transcription-quantitative polymerase chain reaction in rat model. Expression of hub genes did not correlate with mitophagy but was positively correlated with endoplasmic reticulum stress (ERS), which suggested that there may be differences in ERS between different patterns of m5C-based modification. This present study explored and discovered the close link between m5C regulators-related genes and SCI. We also hope our findings may contribute to further mechanistic and therapeutic research on the role of key m5C regulators after SCI.

The extensive morbidity of colorectal cancer (CRC) and the inferior prognosis of terminal CRC urgently call for reliable prognostic biomarkers. For this, we identified 704 differentially expressed genes (DEGs) by intersecting three datasets, GSE41328, GSE37364, and GSE15960 from Gene Expression Omnibus database, to maximize the accuracy of the results. Preliminary analysis of the DEGs was then performed using online gene analysis datasets, such as DAVID, UCSC Cancer Genome Browser, CBioPortal, STRING, and UCSC Cancer Genome Browser. Cytoscape was utilized to visualize the protein perception interaction network of DEGs, and the bubble map of GO and KEGG enrichment function was demonstrated using the R package. The Molecular Complex Detection (MCODE), Biological Network Gene Oncology (BiNGO) plug-in in Cytoscape, was applied to further screen the DEGs to obtain 15 seed genes, which were IL1RN, GALNT12, ADH6, SCN7A, CXCL1, FGF18, SOX9, ACACB, PRRX1, MZB1, SLC22A3, CNNM4, LY6E, IFITM2, and GDPD3. Among them, IL1RN, ADH6, SCN7A, ACACB, MZB1, and GDPD3 exhibited statistically significant survival differences, whereas limited studies were conducted in CRC. Based on the enrichment results of the "Gene Ontology"(GO) and "Kyoto Encyclopedia of Genes and genomes "(KEGG) as well as documented findings of key genes, we further emphasized the potential of IL1RN and PRRX1 as markers of immune infiltrates in CRC and confirmed our hypothesis by compiling data from the UALCAN, Tumor Immune Estimation Resource, and TISIDB databases for these two genes. The above-mentioned genes might offer a valuable insight into the diagnosis, immunotherapeutic targets, and prognosis of CRC.

Bacillus megaterium is well known as a plant growth-promoting rhizobacterium, but the relevant molecular mechanisms remain unclear. This study aimed to elucidate the effects of B. megaterium HT517 on the growth and development of and the control of disease in greenhouse tomato and its mechanism of action. A pot experiment was conducted to determine the effect of B. megaterium on tomato growth, and this experiment included the HT517 group (3.2 × 10⁸ cfu/pot) and the control group (inoculated with the same amount of sterilized suspension). An antagonistic experiment and a plate confrontation experiment were conducted to study the antagonistic effect of B. megaterium and Fusarium oxysporum f.sp. lycopersici. Liquid chromatography-mass spectrometry was used to determine the metabolite composition and metabolic pathway of HT517. PacBio+Illumina HiSeq sequencing was utilized for map sequencing of the samples. An in-depth analysis of the functional genes related to the secretion of these substances by functional bacteria was conducted. HT517 could secrete organic acids that solubilize phosphorus, promote root growth, secrete auxin, which that promotes early flowering and fruiting, and alkaloids, which control disease, and reduce the incidence of crown rot by 51.0%. The complete genome sequence indicated that the strain comprised one circular chromosome with a length of 5,510,339 bp (including four plasmids in the genome), and the GC content accounted for 37.95%. Seven genes (pyk, aceB, pyc, ackA, gltA, buk, and aroK) related to phosphate solubilization, five genes (trpA, trpB, trpS, TDO2, and idi) related to growth promotion, eight genes (hpaB, pheS, pheT, ileS, pepA, iucD, paaG, and kamA) related to disease control, and one gene cluster of synthetic surfactin were identified in this research. The identification of molecular biological mechanisms for extracellular secretion by the HT517 strain clarified that its organic acids solubilized phosphorus, that auxin promoted growth, and that alkaloids controlled tomato diseases.

Hepatocellular carcinoma (HCC) is a common human malignancy with high mortality and dismal prognosis. A growing number of novel targets underlying HCC pathophysiology have been detected using microarray high throughput screening platforms. This study carried out bioinformatics analysis to explore underlying biomarkers in HCC and assessed the potential action of the miR-193b-3p/CDK1 signaling pathway in HCC progression. A total of 241 common differentially expressed genes (DEGs) were screened from GSE33294, GSE104310, and GSE144269. Functional analysis results implicated that DEGs are significantly associated with "cell cycle," "cell division," and "proliferation." The protein-protein interaction network analysis extracted ten hub genes from common DEGs. Ten hub genes were significantly overexpression in HCC tissues. Kaplan-Meier survival analysis revealed that 10 hub genes were linked with a poorer prognosis in HCC patients. Functional assays showed that CDK1 knockdown repressed HCC cell proliferation and migration. Luciferase reporter assay showed that miR-193b-3p could target CDK1 3' untranslated region, and miR-193b-3p negatively modulated CDK1. Enforced CDK1 expression attenuated miR-193b-3p-modulated suppressive actions on HCC cell proliferation and migration. To summarize, we performed a comprehensive bioinformatics analysis and identified 10 hub genes linked to the prognosis in HCC patients. Functional analysis revealed that CDK1, negatively regulated by miR-193b-3p, may act as an oncogene to promote HCC cell proliferation and migration and may predict poor prognosis of HCC patients. However, the role of CDK1/miR-193b-3p may still require further investigation.

Objective: Spinal cord ischemia-reperfusion injury (SCIRI) can cause a pathological state of irreversible delayed death of neurons in the spinal cord tissue and a range of complications, such as spinal cord dysfunction and motor function impairment. This study aimed to determine whether the long-stranded non-coding ribonucleic acid (lncRNA), myocardial infarction-associated transcript (MIAT), could upregulate neuronal growth regulator 1 (NEGR1) by competing for miR-150-5p as a competitive endogenous RNA in a rat SCIRI model.

Methods: The MIAT knockdown vector or the corresponding blank vector was injected into the spinal cord of healthy sprague Dawley (SD) rats. Administration of the MIAT knockdown vector led to the establishment of the SCIRI rat model. Basso, Beattie & Bresnahan locomotor rating scale (BBB) assessment of hind limb motion. Pathological changes in the spinal cord were observed via hematoxylin and eosin staining and eosin staining. Quantitative polymerase chain reaction was performed to determine the expression levels of the candidate microRNAs and predicted candidate genes, and the relationship between them. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining was used to detect apoptosis in the spinal cord tissue of rats in each group. Western blotting was performed to determine the expression of the apoptosis-related proteins, caspase-9, caspase-3, and BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2). The luciferase reporter gene was used to assess the interaction among the lncRNA, MIAT, and miR-150-5, and the interaction between miR-150-5 and NEGR1.

Results: The sh-lncRNA, MIAT, improved exercise status, and pathological changes in the spinal cord of SCIRI rats, inhibited apoptosis, increased the expression of miR-150-5p, and reduced the expression of NEGR1. Compared with mimics-NC, the transfection of miR-150-5p significantly decreased the relative fluorescence activity ratio of MIAT 3'-untranslated region (3'-UTR) wild-type Human embryonic kidney cells 293 (HEK-293 cells). Compared with mimics-negative control (NC), the transfection of miR-150-5p significantly decreased the relative fluorescence activity ratio of NEGR1 3'-UTR wild-type HEK-293 cells.

Conclusion: MIAT can affect the symptoms of SCIRI in rats. Furthermore, as a competitive endogenous RNA, MIAT upregulates NEGR1 by competing with miR-150-5p in SCIRI rats.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC.

Methods: A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis.

Results: After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793-0.994) and 0.812 (95% CI, 0.675-0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC (AUC = 0.953).

Conclusion: The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.