International Journal of Genomics最新文献

Background: Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers, accounting for around 80% of total lung cancer cases worldwide. Exploring the function and mechanism of circRNAs could provide insights into the diagnosis and treatment for NSCLC.

Methods: In this study, we collected tumor tissues and adjacent normal tissues from NSCLC patients to detect the expression level of circPTN and analyzed the association of its expression level with the clinicopathological parameter of NSCLC patients. Moreover, the functional engagement of circPTN in NSCLC cells was examined by cell counting kit-8 (CCK-8) cell proliferation assay, transwell migration and invasion assays, and tube formation assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) analysis were used to detect gene and protein expression, respectively. The molecular targets of cicrPTN were predicted using starBase online resources, which was validated by RNA immunoprecipitation (RIP) and dual-luciferase reporter assay.

Results: Compared with adjacent normal tissues, there was a remarkable increase of the circPTN levels in NSCLC tissues. A high level of circPTN expression was associated with more lymph node metastasis (LNM) and advanced TNM stages. Functionally, circPTN knockdown inhibited the proliferation, migration, and invasion and tube formation ability of NSCLC cells. We further demonstrated that circPTN regulated the malignant phenotype of NSCLC cells through targeting the miR-432-5p/E2F2 axis.

Conclusion: Together, our results suggest that circPTN, which is upregulated in NSCLC tissues, could serve as a prognostic marker for NSCLC patients. circPTN regulates the malignant progression of NSCLC cells through targeting the miR-432-5p/E2F2 axis, which may be employed as a potential strategy for the management of NSCLC.

Microbial genes and their product were diverse and beneficial for heavy metal bioremediation from the contaminated sites. Screening of genes and gene products plays a significant role in the detoxification of pollutants. Understanding of the promoter region and its regulatory elements is a vital implication of microbial genes. To the best of our knowledge, there is no in silico study reported so far on mer gene families used for heavy metal bioremediation. The motif distribution was observed densely upstream of the TSSs (transcription start sites) between +1 and -350 bp and sparsely distributed above -350 bp, according to the current study. MEME identified the best common candidate motifs of TFs (transcription factors) binding with the lowest e value (7.2e-033) and is the most statistically significant candidate motif. The EXPREG output of the 11 TFs with varying degrees of function such as activation, repression, transcription, and dual purposes was thoroughly examined. Data revealed that transcriptional gene regulation in terms of activation and repression was observed at 36.4% and 54.56%, respectively. This shows that most TFs are involved in transcription gene repression rather than activation. Likewise, EXPREG output revealed that transcriptional conformational modes, such as monomers, dimers, tetramers, and other factors, were also analyzed. The data indicated that most of the transcriptional conformation mode was dual, which accounts for 96%. CpG island analysis using online and offline tools revealed that the gene body had fewer CpG islands compared to the promoter regions. Understanding the common candidate motifs, transcriptional factors, and regulatory elements of the mer operon gene cluster using a machine learning approach could help us better understand gene expression patterns in heavy metal bioremediation.

More and more evidence suggests the oncogenic function of overexpressed CDC28 protein kinase regulatory subunit 2 (CKS2) in various human cancers. However, CKS2 has rarely been studied in cervical cancer. Herein, taking advantage of massive genetics data from multicenter RNA-seq and microarrays, we were the first group to perform tissue microarrays for CKS2 in cervical cancer. We were also the first to evaluate the clinical significance of CKS2 with large samples (980 cervical cancer cases and 422 noncancer cases). We further excavated the mechanism of the tumor-promoting activities of CKS2 in cervical cancer through analysis of genetic mutation profiles, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) significant enrichment of genes coexpressed with CKS2. According to the results, expression data from multilevels unanimously supported the overexpression of CKS2 in cervical cancer. Patients with cervical cancer in stage II from inhouse microarrays had significantly higher expression of CKS2, and CKS2 overexpression had an adverse impact on the disease-free survival status of cervical cancer patients in GSE44001. Both mutation types of mRNA high and mRNA low appeared in cervical cancer cases from the TCGA Firehose project. Gene coexpressed with CKS2 participated in pathways including the cell cycle, estrogen signaling pathway, and DNA replication. In summary, upregulated CKS2 is closely associated with the malignant clinical development of cervical cancer and might serve as a valuable therapeutic target in cervical cancer.

Somatic embryogenesis (SE), which occurs naturally in many plant species, serves as a model to elucidate cellular and molecular mechanisms of embryo patterning in plants. Decoding the regulatory landscape of SE is essential for its further application. Hence, the present study was aimed at employing Weighted Gene Correlation Network Analysis (WGCNA) to construct a gene coexpression network (GCN) for Arabidopsis SE and then identifying highly correlated gene modules to uncover the hub genes associated with SE that may serve as potential molecular targets. A total of 17,059 genes were filtered from a microarray dataset comprising four stages of SE, i.e., stage I (zygotic embryos), stage II (proliferating tissues at 7 days of induction), stage III (proliferating tissues at 14 days of induction), and stage IV (mature somatic embryos). This included 1,711 transcription factors and 445 EMBRYO DEFECTIVE genes. GCN analysis identified a total of 26 gene modules with the module size ranging from 35 to 3,418 genes using a dynamic cut tree algorithm. The module-trait analysis revealed that four, four, seven, and four modules were associated with stages I, II, III, and IV, respectively. Further, we identified a total of 260 hub genes based on the degree of intramodular connectivity. Validation of the hub genes using publicly available expression datasets demonstrated that at least 78 hub genes are potentially associated with embryogenesis; of these, many genes remain functionally uncharacterized thus far. In silico promoter analysis of these genes revealed the presence of cis-acting regulatory elements, "soybean embryo factor 4 (SEF4) binding site," and "E-box" of the napA storage-protein gene of Brassica napus; this suggests that these genes may play important roles in plant embryo development. The present study successfully applied WGCNA to construct a GCN for SE in Arabidopsis and identified hub genes involved in the development of somatic embryos. These hub genes could be used as molecular targets to further elucidate the molecular mechanisms underlying SE in plants.

Hepatocellular carcinoma (HCC) represents a common malignancy, and mechanisms of acquired sorafenib resistance during the treatment of HCC patients remain elusive. The present study performed integrated bioinformatics analysis and explored the potential action of heme oxygenase 1 (HMOX1) in sorafenib-resistant HCC cells. Differentially expressed genes (DEGs) of the sorafenib-resistant group as compared to the sorafenib-sensitive group from GSE140202 and GSE143233 were extracted. Fifty common DEGs between GSE140202 and GSE143233 were extracted. Ten hub genes were identified from the protein-protein interaction network based on common DEGs. Experimental results revealed the upregulation of HMOX1 in sorafenib-resistant HCC cells. HMOX1 silence promoted the sensitivity to sorafenib in sorafenib-resistant HCC cells; overexpression of HMOX1 attenuated the sensitivity. In addition, HMOX1 silence downregulated the mRNA expression of ABC transporters in sorafenib-resistant HCC cells, while HMOX1 overexpression upregulated mRNA expression of ABC transporter expression in HCC cells. Further analysis also revealed that high expression of HMOX1 was associated with shorter OS and DSS in HCC patients. In conclusion, our analysis identified ten hub genes associated with sorafenib resistance in HCC. Further validation studies demonstrated that HMOX1 promoted sorafenib resistance of HCC cells via modulating ABC transporter expression.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with a high mortality rate. The tumor microenvironment (TME) is composed of numerous noncancerous cells that contribute to tumorigenesis and prediction of therapeutic effects. In this study, we aimed to develop a cell component-related prognostic model based on TME. We screened cell component enrichments from samples in The Cancer Genome Atlas (TCGA) HNSCC cohort using the xCell algorithm. Univariate Cox and multivariate Cox regression analyses were performed to establish an optimal independent risk model. The prognostic value of the model was further validated using Gene Expression Omnibus datasets. We found that patients in the low-risk group had a better outcome and activated immunity and may benefit more from the immune checkpoint inhibitor therapy. We also explored microRNAs (miRNAs) that may regulate these identified cell components, and 11 miRNA expression levels influenced the overall survival time. Moreover, their target mRNAs were differentially expressed in TCGA cohort and enriched in pathways of cell cycle pathways, extracellular matrix receptor interaction, human papillomavirus infection, and cancer. In summary, our cell component-related signature was a promising prognostic biomarker that provides new insights into the predictive value of nontumor components in the TME.

Plants being sessile are always exposed to various environmental stresses, and to overcome these stresses, modifications at the epigenetic level can prove vital for their long-term survival. Epigenomics refers to the large-scale study of epigenetic marks on the genome, which include covalent modifications of histone tails (acetylation, methylation, phosphorylation, ubiquitination, and the small RNA machinery). Studies based on epigenetics have evolved over the years especially in understanding the mechanisms at transcriptional and posttranscriptional levels in plants against various environmental stimuli. Epigenomic changes in plants through induced methylation of specific genes that lead to changes in their expression can help to overcome various stress conditions. Recent studies suggested that epigenomics has a significant potential for crop improvement in plants. By the induction and modulation of various cellular processes like DNA methylation, histone modification, and biogenesis of noncoding RNAs, the plant genome can be activated which can help in achieving a quicker response against various plant stresses. Epigenetic modifications in plants allow them to adjust under varied environmental stresses by modulating their phenotypic plasticity and at the same time ensure the quality and yield of crops. The plasticity of the epigenome helps to adapt the plants during pre- and postdevelopmental processes. The variation in DNA methylation in different organisms exhibits variable phenotypic responses. The epigenetic changes also occur sequentially in the genome. Various studies indicated that environmentally stimulated epimutations produce variable responses especially in differentially methylated regions (DMR) that play a major role in the management of stress conditions in plants. Besides, it has been observed that environmental stresses cause specific changes in the epigenome that are closely associated with phenotypic modifications. However, the relationship between epigenetic modifications and phenotypic plasticity is still debatable. In this review, we will be discussing the role of various factors that allow epigenetic changes to modulate phenotypic plasticity against various abiotic stress in plants.

Gastric cancer (GC) is a common digestive tumor which ranks the fourth most common malignancy worldwide. Immunotherapy is a promising treatment for GC, especially for advanced gastric cancer (AGC). However, in clinical practice, not all patients are sensitive to immunotherapy. Recent studies showed that tumor mutation burden (TMB) is closely correlated with the response of immunotherapy. The current study identified a TMB-related genes' signature to predict the prognosis and immune feature of GC patients. Firstly, we acquired the TMB data and expression data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) GEO databases. Then, we extracted TMB-related genes from the expression data of TCGA and two GEO cohorts. By using univariate Cox analysis, we identified that the 429 genes were correlated to GC patients' overall survival. Subsequently, an immune prognostic signature was constructed by using the least absolute shrinkage and selection operator analysis (LASSO) and multivariate Cox regression analysis. The signature could be utilized to predict the prognosis of GC patients. In addition, the signature showed a closed correlation with immune feature of GC patients. In conclusion, our risk signature could offer hints for the prognosis of GC patients and might provide insights to formulate new immunotherapy strategies for GC patients.