Comparative and Functional Genomics最新文献

Aim. To investigate the specific expression profile, clinicopathological significance and mechanism of Zic family member 2 (ZIC2) in oral cancer were unclear. Patients and Methods. We explored the expression pattern and clinicopathological significance of ZIC2 in oral cancer through performing in-house tissue microarray and integrated analysis global RNA-seq and microarrays containing large samples. The molecular basis of ZIC2 in oral cancer was further investigated in the aspects of transcription network and immune correlations. We also performed in vitro experiments and calculated drug sensitivity of oral cancer with different ZIC2 expression levels in response to hundreds of compounds. Results. All data unanimously proved the significant overexpression of ZIC2 in oral cancer. The upregulation of ZIC2 was remarkably associated with the malignant clinical progression of oral cancer. ZIC2 was predicted to be targeted by miRNAs such as miR-3140, miR-4999, and miR-1322. The infiltration level of CD8+ T and central memory cells was positively related to the overexpression of ZIC2. Oral cancer patients with higher ZIC2 expression showed higher drug sensitivity to two compounds including AZD8186 and ERK_2240. Conclusions. We demonstrated the upregulation of ZIC2 in oral cancer and its promoting effect on the clinical advancement of oral cancer. The potential clinical value of ZIC2 in oral cancer deserves attention.

Water deficit is a key limiting factor for limiting yield in maize (Zea mays L.). It is crucial to elucidate the molecular regulatory networks of stress tolerance for genetic enhancement of drought tolerance. The mechanism of drought tolerance of maize was explored by comparing physiological and transcriptomic data under normal conditions and drought treatment at polyethylene glycol- (PEG-) induced drought stress (5%, 10%, 15%, and 20%) in the root during the seedling stage. The content of saccharide, SOD, CAT, and MDA showed an upward trend, proteins showed a downward trend, and the levels of POD first showed an upward trend and then decreased. Compared with the control group, a total of 597, 2748, 6588, and 5410 differentially expressed genes were found at 5%, 10%, 15%, and 20% PEG, respectively, and 354 common DEGs were identified in these comparisons. Some differentially expressed genes were remarkably enriched in the MAPK signaling pathway and plant hormone signal transduction. The 50 transcription factors (TFs) divided into 15 categories were screened from the 354 common DEGs during drought stress. Auxin response factor 10 (ARF10), auxin-responsive protein IAA9 (IAA9), auxin response factor 14 (ARF14), auxin-responsive protein IAA1 (IAA1), auxin-responsive protein IAA27 (IAA27), and 1 ethylene response sensor 2 (ERS2) were upregulated. The two TFs, including bHLH 35 and bHLH 96, involved in the MAPK signal pathway and plant hormones pathway, are significantly upregulated in 5%, 10%, 15%, and 20% PEG stress groups. The present study provides greater insight into the fundamental transcriptome reprogramming of grain crops under drought.

Molecular markers are increasingly being deployed to accelerate genetic gain in crop plants. The objective of this study was to assess the potential of a mid-density genotyping panel for molecular applications in cowpea breeding. A core set of 2,602 targeted diversity array technology (DArTag) single-nucleotide polymorphisms (SNPs) was designed from an existing 51,128 Cowpea iSelect Consortium Array. The panel’s usefulness was assessed using 376 genotypes from different populations of known genetic backgrounds. The panel was informative, with over 78% of SNPs exceeding a minor allele frequency of 0.20. The panel decoded three stratifications in the constituted population, as was expected. Linkage disequilibrium (LD) decay was correctly depicted as slower in a biparental subset than in other populations. A known flower and seed coat color gene region was located on chromosome Vu07, suggesting that the mid-density panel may be used to hypothesize genomic regions underlying target traits in cowpea. Unexpected heterozygosity was detected in some lines and highly among F₁ progenies, divulging the panel’s potential application in germplasm purity and hybridity verification. The study unveils the potential of an excellent genomic resource that can be tapped to enhance the development of improved cowpea cultivars.

Background. Gastric cancer (GC) is the second most frequent cause of cancer-related death worldwide and the fourth most common malignancy. Despite significant improvements in patient survival over the past few decades, the prognosis for patients with GC remains dismal because of the high recurrence rate. In this comprehensive system biology and experimental investigation, we aimed to find new novel diagnostic biomarkers of GC through a regulatory RNA interaction network. Methods. Gene expression, coexpression, and survival analyses were performed using microarray and RNAseq datasets (analyzed by RStudio, GEPIA2, and ENCORI). RNA interaction analysis was performed using miRWalk and ENCORI online databases. Gene set enrichment analysis (GSEA) was performed to find related signaling pathways of up- and downregulated genes in the microarray dataset. Gene ontology and pathway enrichment analysis were performed by the enrichr database. Protein interaction analysis was performed by STRING online database. Validation of expression and coexpression analyses was performed using a qRT-PCR experiment. Results. Based on bioinformatics analyses, THBS2 (FC: 7.14, FDR < 0.0001) has a significantly high expression in GC samples. lncRNAs BAIAP2-AS1, TSIX, and LINC01215 have RNA interaction with THBS2. BAIAP2-AS1 (FC: 1.44, FDR: 0.018), TSIX (FC: 1.34, FDR: 0.038), and LINC01215 (FC: 1.19, FDR: 0.046) have significant upregulation in GC samples. THBS2 has a significant role in the regulation of the ECM-receptor signaling pathway. miR-4677-5p has a significant RNA interaction with THBS2. The expression level of THBS2, BAIAP2-AS1, TSIX, and LINC01215 has a nonsignificant negative correlation with the survival rate of GC patients (HR: 0.28, logrank p: 0.28). qRT-PCR experiment validates mentioned bioinformatics expression analyses. BAIAP2-AS1 (AUC: 0.7136, p value: 0.0096), TSIX (AUC: 0.7456, p value: 0.0029), and LINC01215 (AUC: 0.7872, p value: 0.0005) could be acceptable diagnostic biomarkers of GC. Conclusion. BAIAP2-AS1, lncRNA LINC01215, lncRNA TSIX, and miR-4677-5p might modulate the ECM-receptor signaling pathway via regulation of THBS2 expression level, as the high-expressed noncoding RNAs in GC. Furthermore, mentioned lncRNAs could be considered potential diagnostic biomarkers of GC.

Background. Ubiquitin-related proteins have garnered increasing attention for their roles in tumorigenesis. Transmembrane and ubiquitin-like domain-containing 1 (TMUB1) is a recently discovered protein in the ubiquitin-like domain family, yet its involvement in glioma remains poorly understood. This study is aimed at investigating the functional significance and clinical relevance of TMUB1 in glioma. Methods. We conducted a comprehensive analysis using two cohorts: a retrospective glioma cohort from our hospital and The Cancer Genome Atlas (TCGA) cohort. The mRNA levels of TMUB1 were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical associations of TMUB1 in these cohorts were evaluated using correlation tests, chi-square tests, and survival analyses. Additionally, we performed TMUB1 knockdown in U87 and LN-229 human glioma cell lines, and cellular growth was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results. Our results revealed that TMUB1 expression was elevated in glioma tissues compared to normal brain tissues. Notably, lower TMUB1 expression correlated with favorable characteristics such as lower World Health Organization (WHO) grade and 1p/19q codeletion. Moreover, patients with higher TMUB1 levels in glioma tissues exhibited worse prognosis in both TCGA cohort and our retrospective cohort, underscoring its prognostic significance in gliomas. Cellular experiments demonstrated that TMUB1 silencing suppressed the growth of glioma cells. Conclusions. TMUB1 emerges as a novel and clinically relevant prognostic biomarker for gliomas. Targeting TMUB1 holds promise as a potential strategy for glioma treatment. This study contributes valuable insights into the multifaceted role of TMUB1 in glioma pathogenesis and its potential as a diagnostic and therapeutic target.

Breast cancer (BC) has emerged as an extremely destructive malignancy, causing significant harm to female patients and society at large. Proteomic research holds great promise for early diagnosis and treatment of diseases, and the integration of proteomics with genomics can offer valuable assistance in the early diagnosis, treatment, and improved prognosis of BC patients. In this study, we downloaded breast cancer protein expression data from The Cancer Genome Atlas (TCGA) and combined proteomics with genomics to construct a proteomic-based prognostic model for BC. This model consists of nine proteins (HEREGULIN, IDO, PEA15, MERIT40_pS29, CIITA, AKT2, CD171 DVL3, and CABL9). The accuracy of the model in predicting the survival prognosis of BC patients was further validated through risk curve analysis, survival curve analysis, and independent prognostic analysis. We further confirmed the impact of differential expression of these nine key proteins on overall survival in BC patients, and the differential expression of the key proteins and their encoding genes was validated using immunohistochemical staining. Enrichment analysis revealed functional associations primarily related to PPAR signaling pathway, steroid hormone metabolism, chemokine signaling pathway, DNA conformation changes, immunoglobulin production, and immunoglobulin complex in the high- and low-risk groups. Immune infiltration analysis revealed differential expression of immune cells between the high- and low-risk groups, providing a theoretical basis for subsequent immunotherapy. The model constructed in this study can predict the survival of BC patients, and the identified key proteins may serve as biomarkers to aid in the early diagnosis of BC. Enrichment analysis and immune infiltration analysis provide a necessary theoretical basis for further exploration of the molecular mechanisms and subsequent immunotherapy.

Colon adenocarcinoma, a highly prevalent and aggressive form of colorectal cancer, necessitates a comprehensive understanding of its molecular mechanisms to identify potential therapeutic targets. The Krüppel-like factor 7 (KLF7), a transcription factor, has been associated with various malignancies, yet its specific role in colon adenocarcinoma remains largely unexplored. Here, we aimed to determine the expression and functional significance of KLF7 in colon adenocarcinoma. Our findings revealed a significant upregulation of KLF7 expression in colon adenocarcinoma tissues compared to adjacent normal tissues. Moreover, elevated KLF7 expression correlated with advanced tumor stage, lymph node metastasis, and poor overall survival in colon adenocarcinoma patients. Functional assays demonstrated that silencing KLF7 resulted in reduced cell proliferation, migration, and invasion, indicating its involvement in promoting tumor growth and metastasis. Additionally, we identified potential downstream targets of KLF7, including genes associated with cell cycle regulation and epithelial-mesenchymal transition. These results underscore the tumor-promoting role of KLF7 in colon adenocarcinoma, positioning it as a potential prognostic biomarker and therapeutic target for this aggressive disease.

Pancreatic adenocarcinoma (PAAD) is a malignancy with the highest mortality rate worldwide. There is a pressing need for novel biomarkers that can facilitate early detection and serve as targets for therapeutic interventions beyond the commonly utilized CA199 marker. This study utilized microarray datasets (GSE15471, GSE62165, and GSE28735) from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) and construct a protein-protein interaction network using STRING and Cytoscape. Hub genes were selected using BiNGO. Expression profiles and clinical data from the Cancer Genome Atlas (TCGA) were then used to compare the expression levels of CTSK and PLAU in pancreatic cancer and healthy pancreatic tissues via the Wilcoxon rank-sum test, with further validation using qPCR. Functional enrichment analysis was conducted to explore potential signaling pathways and biological functions. Prognostic values were assessed by the Kaplan-Meier and Cox regression analyses, and an overall survival (OS) nomogram was created to predict 1-, 2-, and 3-year survival after cancer diagnosis. The infiltration of immune cells was evaluated by single-sample gene set enrichment analysis. The methylation status of both genes was analyzed using the UALCAN and MethSurv databases. The results demonstrated that CTSK and PLAU were overexpressed in pancreatic cancer and that the hypomethylation status of both genes was associated with a poor prognosis. The overexpression of both genes was positively correlated with various immune cells, and functional enrichment analysis revealed that they were associated with immune cell infiltration. Besides, the effects of PLAU on the migration and invasion of pancreatic cancer cells were also verified by scratch and transwell experiments. Consequently, CTSK and PLAU have potential as prognostic biomarkers for pancreatic cancer.

Background. Currently, the role of oncostatin M (OSM) in clear cell renal cell carcinoma (ccRCC) has not been investigated. This study will explore the impact of OSM on ccRCC expression, prognosis, and cell function. Materials and Methods. In this study, we used The Cancer Genome Atlas (TCGA) database to evaluate OSM expression characteristics, pathogenic factor distribution, and prognostic aspects in ccRCC. We also combined this analysis with qRT-PCR to verify OSM mRNA expression levels at the tissue level. Then, the effects of OSM on the proliferation, invasion, and migration abilities of ccRCC cells were explored through CCK8, Transwell, Western blotting, and immunofluorescence experiments. Finally, the oncogenic mechanisms associated with OSM in ccRCC were explored through signaling pathway enrichment and single-cell analysis. Results. The results demonstrated that OSM was significantly more expressed in ccRCC than in normal tissues. According to the survival analysis, OSM in ccRCC was considerably worse in the group with high expression than in the group with low expression. Also, the univariate and multivariate Cox analyses of clinical characteristics show that OSM in ccRCC may be able to predict a poor prognosis on its own as a biomarker. In vitro cellular experiments demonstrated that high OSM expression had no discernible impact on ccRCC cell proliferation compared to the control group, but it did promote tumor cell invasion and migration. Signaling pathways and single-cell analysis revealed that OSM might promote ccRCC invasion and migration through M2 macrophages. Conclusion. In conclusion, OSM may serve as an independent poor prognostic biomarker in ccRCC and promote tumor cell invasion and migration. This discovery is expected to provide a new therapeutic target for patients with recurrent and metastatic ccRCC.

Background. Kynureninase (KYNU) is a potential prognostic marker for various tumor types. However, no reports on the biological effects and prognostic value of KYNU in gastric cancer (GC) exist. Methods. GC-associated single-cell RNA sequencing and bulk RNA sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of KYNU between GC and normal gastric tissues was first analyzed based on the bulk-seq data, followed by an exploration of the relationship between KYNU and various clinicopathological features. The Kaplan–Meier survival and Cox regression analyses were performed to determine the prognostic value of KYNU. The relationship between KYNU expression and immune cell infiltration and immune checkpoints was also explored. The biological function of KYNU was further examined at the single-cell level, and in vitro experiments were performed to examine the effect of KYNU on GC cell proliferation and invasion. Results. KYNU expression was significantly elevated in GC samples. Clinical features and survival analysis indicated that high KYNU expression was associated with poor clinical phenotypes and prognosis, whereas Cox analysis showed that KYNU was an independent risk factor for patients with GC. Notably, high expression of KYNU induced a poor immune microenvironment and contributed to the upregulation of immune checkpoints. KYNU-overexpressing macrophages drove GC progression through unique ligand-receptor pairs and transcription factors and were associated with adverse clinical phenotypes in GC. KYNU was overexpressed in GC cells in vitro, and KYNU knockout significantly inhibited GC cell proliferation and invasion. Conclusion. High KYNU expression promotes an adverse immune microenvironment and low survival rates in GC. KYNU and KYNU-related macrophages may serve as novel molecular targets in the treatment of GC.