Comparative and Functional Genomics最新文献

Background. Neuroblastoma (NB) is the third most common malignant tumor in children. The inflammation is believed to be closely related to NB patients’ prognosis. However, there is no comprehensive research to study the role of inflammatory response-related gene (IRRG) in NB patients. Methods. We downloaded the gene expression profiles of NB patients from GEO and TARGET database, and the expression of 200 IRRGs was extracted. Then, we performed differentially analysis between INSS stage 4 and INSS stage 4S NB patients. The univariate and multivariate Cox regression analyses were performed to screen out the overall survival- (OS-) and event-free survival- (EFS-) related IRRGs in GSE49710, and two signatures were constructed; both signatures were evaluated by Kaplan-Meier (K-M) survival curve and receiver operating characteristic (ROC) curve. Finally, the TARGET cohort was used to validate IRRG signatures, and the independence of the prognostic IRRG signatures was evaluated by integrating clinical information. Results. We screened out 10 OS-related IRRGs and 11 EFS-related IRRGs. Then, we identified that OS- and EFS-related IRRG signatures and found that the OS and EFS of NB patients in the low-risk group were significantly superior than those in the high-risk group (both P value < 0.0001). The AUC values of 3-, 5-, and 7-year OS are 0.910, 0.933, and 0.921, respectively, and 3-, 5-, and 7-year EFS are 0.840, 0.835, and 0.837, respectively. In addition, we found that both IRRG signatures can be used as independent prognostic indicators for patients with NB. Both IRRG signatures still have good predictive ability in validation cohort. Conclusions. We constructed and validated two prognostic gene signatures based on IRRGs. Our study helped us to better understand the role of inflammation in NB and provided new insights for the prognosis assessment and treatment strategy for NB patients.

Background. Nei endonuclease VIII-like 3 (NEIL3) is widely involved in pathophysiological processes of the body; however, its role in lung cancer has not been conclusively determined. Objective. This study is aimed at exploring the role of NEIL3 in lung cancer. Methods. The public data used in this study were downloaded from The Cancer Genome Atlas (TCGA) database. “Limma” in R was used for the analysis of differentially expressed genes. Clinical correlations and prognostic analyses were performed using the survival package in R. The proliferative abilities of lung cancer cells were evaluated by the CCK8 and colony formation assays while their invasive and migration abilities were assessed by the transwell and wound healing assays. Quantitative real-time PCR (qRT-PCR) and western blot analyses were utilized to detect RNA and protein levels. Biological differences between groups were determined by gene set enrichment analysis (GSEA). Tumor Immune Dysfunction and Exclusion (TIDE) as well as Genomics of Drug Sensitivity in Cancer (GDSC) was used for immunotherapeutic and chemotherapeutic sensitivity analyses. Results. NEIL3 was upregulated in NSCLC tissues and cell lines, implying that it is involved in lung cancer initiation and progression. Clinical correlation and prognostic analyses showed that NEIL3 was associated with worse clinical features (stage and T and N classifications) and poor prognostic outcomes. In vitro, NEIL3 significantly enhanced NSCLC proliferation, invasion, and migration. GSEA indicated that NEIL3 might be involved in PI3K/AKT/mTOR, G2/M checkpoints, and E2F target pathways. Inhibition of NEIL3 suppressed cyclinD1 and p-AKT protein levels; however, it had no effects on AKT levels, indicating that NEIL3 can partially activate the PI3K/AKT/mTOR signaling pathway. The predicted result of TIDE indicated that immunotherapeutic nonresponders had elevated NEIL3 levels. Moreover, there was a positive correlation between NEIL3 levels and chemosensitivity to cisplatin and paclitaxel. Conclusion. In general, NEIL3 mediates NSCLC progression and affects sensitivity to immunotherapy and chemotherapy; therefore, it is a potential molecular target for treatment.

The susceptibility of crop plants towards abiotic stresses is highly threatening to assure global food security as it results in almost 50% annual yield loss. To address this issue, several strategies like plant breeding and genetic engineering have been used by researchers from time to time. However, these approaches are not sufficient to ensure stress resilience due to the complexity associated with the inheritance of abiotic stress adaptive traits. Thus, researchers were prompted to develop novel techniques with high precision that can address the challenges connected to the previous strategies. Genome editing is the latest approach that is in the limelight for improving the stress tolerance of plants. It has revolutionized crop research due to its versatility and precision. The present review is an update on the different genome editing tools used for crop improvement so far and the various challenges associated with them. It also highlights the emerging potential of genome editing for developing abiotic stress-resilient crops.

Background. Common genetic risk variants for prostate cancer (PCa) have been identified at approximately 170 loci using genome-wide association studies (GWAS), most of which were identified in European populations. Recently, GWAS were applied to a large Japanese cohort and identified 12 novel susceptibility loci associated with PCa risk. In this study, we aim to investigate PCa susceptibility loci in the Chinese population. The study data will be used to promote PCa risk control in China. Methods. A total of 235 PCa patients and 252 control subjects (all unrelated) were enrolled in this case-control PCa study. Nine single nucleotide polymorphisms (SNPs) were genotyped in GATA2 (rs73862213, rs2335052, and rs10934857), ZMIZ1 (rs704017, rs77911174, and rs3740259), and SUN2 (rs78397383, rs5750680, and rs138705) genes. The associations between the candidate SNPs and PCa were analyzed using multiple-factor logistic regression and haplotype analysis. Results. The allele frequency distributions of rs73862213 and rs2335052 in the GATA2 gene and rs704017 and rs77911174 in the ZMIZ1 gene were found to be significantly different between PCa cases and controls. Haplotype analysis revealed that the G-C-A haplotype of the GATA2 gene (order of SNPs: rs73862213-rs2335052-rs10934857) and the G-G-G haplotype of the ZMIZ1 gene (order of SNPs: rs704017-rs77911174-rs3740259) were associated with increased PCa risk. None of the SUN2 haplotypes were associated with PCa. Conclusions. Our study data indicates that the minor alleles of rs73862213 and rs2335052 in the GATA2 gene and rs704017 and rs77911174 in the ZMIZ1 gene were associated with increased PCa risk. These findings greatly extended our knowledge of the etiology of PCa.

Objective. To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA. Methods. The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot. Results. YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated. Conclusion. YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.

Non-small-cell lung cancer (NSCLC) is one of the most serious cancers. The circular RNA_0078767 (circ_0078767) expression was decreased in NSCLC tissues. However, the molecular mechanism of circ_0078767 remains unknown. The expression of circ_0078767, microRNA-665 (miR-665), and glutathione peroxidase 3 (GPX3) was detected by quantitative real-time fluorescence polymerase chain reaction (qRT-PCR). Cell proliferation, migration, and invasion were detected by colony formation assay and transwell assay, respectively. The lactate production and glucose consumption were tested by glycolysis. Western blot examined the protein levels of hexokinase-2 (HK2), matrix metalloproteinase-9 (MMP9), and GPX3 cells. Circinteractome predicted the relationship between miR-665 and circ_0078767 or GPX3 and was verified by dual luciferase reporter assays. The xenotransplantation model was established to study the role of circ_0078767 in vivo. The expression of circ_0078767 and GPX3 was decreased in NSCLC tissues, while the expression of miR-665 was increased. Circ_0078767 can sponge miR-665, and GPX3 is the target of miR-665. In vitro complement experiments showed that knockdown of circ_0078767 significantly promoted malignant behavior of NSCLC, while cotransfection of miR-665 inhibitor partially reduced this change. In addition, the GPX3 overexpression decreased the promoting effects of miR-665 upregulation on proliferation, migration, and invasion of NSCLC cells. Mechanically, circ_0078767 regulates the GPX3 expression in NSCLC cells by spongy miR-665. In addition, in vivo studies have shown that downregulation of circ_0078767 promotes tumor growth. Circ_0078767 silencing promotes proliferation, migration, invasion, and glycolysis of NSCLC cells by regulating the miR-665/GPX3 axis, suggesting that circ_0078767/miR-665/GPX3 axis may be a potential regulatory mechanism for the treatment of NSCLC.

Shaker-type K⁺ channels are critical for plant K⁺ acquisition and translocation that play key roles during plant growth and development. However, molecular mechanisms towards K⁺ channels are extremely rare in fruit trees, especially in peach. In this study, we identified 7 putative shaker-type K⁺ channel genes from peach, which were unevenly distributed on 5 chromosomes. The peach shaker K⁺ channel proteins were classified into 5 subfamilies, I-V, and were tightly clustered with pear homologs in the phylogenetic tree. Various cis-acting regulatory elements were detected in the promoter region of the shaker-type K⁺ channel genes, including phytohormone-responsive, abiotic stress-responsive, and development regulatory elements. The peach shaker K⁺ channel genes were expressed differentially in distinct tissues, and PpSPIK was specifically expressed in the full-bloom flowers; PpKAT1 and PpGORK were predominantly expressed in the leaves, while PpAKT1, PpKC1, and PpSKOR were majorly expressed in the roots. The peach shaker K⁺ channel genes were differentially regulated by abiotic stresses in that K⁺ deficiency, and ABA treatment mainly increased the shaker K⁺ channel gene expression throughout the whole seedling, whereas NaCl and PEG treatment reduced the shaker K⁺ channel gene expression, especially in the roots. Moreover, electrophysiological analysis demonstrated that PpSKOR is a typical voltage-dependent outwardly rectifying K⁺ channel in peach. This study lays a molecular basis for further functional studies of the shaker-type K⁺ channel genes in peach and provides a theoretical foundation for K⁺ nutrition and balance research in fruit trees.

The availability of comprehensive genomic datasets across patient populations enables the application of novel methods for reconstructing tumor evolution within individual patients. To this end, we propose studying autosomal broad copy number alterations (CNAs) as a framework to better understand early tumor evolution. We compared the broad CNAs and somatic mutations of patients with 1 to 10 autosomal broad CNAs against the full set of patients, using data from The Cancer Genome Atlas breast cancer project. We reveal here that the frequency of a chromosome arm obtaining a broad CNA and a genome acquiring somatic mutations changes as autosomal broad CNAs accumulate. Therefore, we propose that the number of autosomal broad CNAs is an important characteristic of breast tumors that needs to be taken into consideration when studying breast tumors. To investigate this idea more in-depth, we next studied the frequency that specific chromosome arms acquire broad CNAs in patients with 1 to 10 broad CNAs. With this process, we identified the broad CNAs that exhibit the fastest rates of accumulation across all patients. This finding suggests a likely order of occurrence of these alterations in patients, which is apparent when we consider a subset of patients with few broad CNAs. Here, we lay the foundation for future studies to build upon our findings and use autosomal broad CNAs as a method to monitor breast tumor progression in vivo to further our understanding of how early tumor evolution unfolds.

The fruiting bodies or mycelia of Hericium coralloides (H. coralloides) contain many physiologically active compounds that are used to treat various diseases, including cardiovascular disorders and cancers. However, the genome of H. coralloides has not been sequenced, which hinders further investigations into aspects, such as bioactivity or evolutionary events. The present study is aimed at (i) performing de novo sequencing of the assembled genome; (ii) mapping the reads from PE400 DNA into the assembled genome; (iii) identifying the full length of all the repeated sequences; and (iv) annotating protein-coding genes using GO, eggNOG, and KEGG databases. The assembled genome comprised 5,59,05,675 bp, including 307 contigs. The mapping rate of reads obtained from PE400 DNA in the assembled genome was 92.46%. We identified 2,525 repeated sequences of 14,23,274 bp length. We predicted ncRNAs of 48,895 bp and 11,736 genes encoding proteins that were annotated in the GO, eggNOG, and KEGG databases. We are the first to sequence the entire H. coralloides genome (NCBI; Assembly: ASM367540v1), which will serve as a reference for studying the evolutionary diversification of edible and medicinal mushrooms and facilitate the application of bioactivity in H. coralloides.

Phenomics and chlorophyll fluorescence can help us to understand the various stresses a plant may undergo. In this research work, we observe the image-based morphological changes in the wheat canopy. These changes are monitored by capturing the maximum area of wheat canopy image that has maximum photosynthetic activity (chlorophyll fluorescence signals). The proposed algorithm presented here has three stages: (i) first, derivation of dynamic threshold value by curve fitting of data to eliminate the pixels of low-intensity value, (ii) second, extraction and segmentation of thresholded region by application of histogram-based K-means algorithm iteratively (this scheme of the algorithm is referred to as the curve fit K-means (CfitK-means) algorithm); and (iii) third, computation of 23 grey level cooccurrence matrix (GLCM) texture features (traits) from the wheat images has been done. These features help to do statistical analysis and infer agronomical insights. The analysis consists of correlation, factor, and agglomerative clustering to identify water stress indicators. A public repository of wheat canopy images was used that had normal and water stress response chlorophyll fluorescence images. The analysis of the feature dataset shows that all 23 features are proved fruitful in studying the changes in the shape and structure of wheat canopy due to water stress. The best segmentation algorithm was confirmed by doing exhaustive comparisons of seven segmentation algorithms. The comparisons showed that the best algorithm is CfitK-means as it has a maximum IoU score value of 95.75.