Integrated analysis of the ubiquitination mechanism reveals the specific signatures of tissue and cancer.

BACKGROUND: Ubiquitination controls almost all cellular processes. The dysregulation of ubiquitination signals is closely associated with the initiation and progression of multiple diseases. However, there is little comprehensive research on the interaction and potential function of ubiquitination regulators (UBRs) in spermatogenesis and cancer. METHODS: We systematically characterized the mRNA and protein expression of UBRs across tissues and further evaluated their roles in testicular development and spermatogenesis. Subsequently, we explored the genetic alterations, expression perturbations, cancer hallmark-related pathways, and clinical relevance of UBRs in pan-cancer. RESULTS: This work reveals heterogeneity in the expression patterns of UBRs across tissues, and the expression pattern in testis is the most distinct. UBRs are dynamically expressed during testis development, which are critical for normal spermatogenesis. Furthermore, UBRs have widespread genetic alterations and expression perturbations in pan-cancer. The expression of 79 UBRs was identified to be closely correlated with the activity of 32 cancer hallmark-related pathways, and ten hub genes were screened for further clinical relevance analysis by a network-based method. More than 90% of UBRs can affect the survival of cancer patients, and hub genes have an excellent prognostic classification for specific cancer types. CONCLUSIONS: Our study provides a comprehensive analysis of UBRs in spermatogenesis and pan-cancer, which can build a foundation for understanding male infertility and developing cancer drugs in the aspect of ubiquitination.

Dynamic Expression of Palmitoylation Regulators across Human Organ Development and Cancers Based on Bioinformatics.

Protein palmitoylation is a reversible modification process that links palmitate to cysteine residues via a reversible thioester bond. Palmitoylation exerts an important role in human organ development and tumor progression. However, a comprehensive landscape regarding the dynamic expression of palmitoylation regulators in human organ development remains unclear. In this study, we analyzed the dynamic expression of palmitoylation regulators in seven organ development and eight cancer types based on bioinformatics. We found that the expression levels of most palmitoylation regulators were altered after birth. In particular, ZDHHC7/20/21 exhibited converse expression patterns in multiple cancer types. Survival analysis showed that the poor prognosis in patients with kidney renal clear carcinoma (KIRC) is related to low expression of ZDHHC7/20/21, and a high expression of ZDHHC7/20/21 is related to worse survival in patients with liver hepatocellular carcinoma (LIHC). Furthermore, we found that the expression of ZDHHC7 is associated with infiltration levels of some types of immune cells in the tumor microenvironment (TME), and we explored the relationship between ZDHHC7 expression and immune checkpoint (ICP) genes across 33 cancer types. In addition, gene set enrichment analysis (GSEA) results indicated that ZDHHC7 might regulate different genes to mediate the same pathway in different organs. In summary, the comprehensive analysis of palmitoylation regulators reveals their functions in human organ development and cancer, which may provide new insights for developing new tumor markers.

Single-cell transcriptome analysis of Bisphenol A exposure reveals the key roles of the testicular microenvironment in male reproduction.

Testicular development during juvenile is crucial for subsequent male reproductive function. However, it remains poorly understood about the contribution of the testis microenvironment to human germ cell maturation. Therefore, we systematically analyzed scRNA-seq transcriptome and found the dramatic changes in cell-type composition in human testis during puberty. Then we constructed cell-cell communication networks between germ cells and somatic cells in the juvenile testis, which may be achieved via immune-related pathways. Our results showed that maturation-promoting factors are the switches of the Sertoli cells that drive sperm maturation. Furthermore, we found that Bisphenol A(BPA) enhanced the maturation and growth of germ cells through the Sertoli cell's secretory protein. Finally, our results indicate Bisphenol A would lead to the dysregulation of secreted protein expression in Sertoli cells during spermatogenesis, which in turn has direct cytotoxicity to Sertoli cells. Bisphenol A is one of the underlying causes of non-obstructive azoospermia (NOA). In summary, our results reveal the reproductive toxicity and molecular mechanism of Bisphenol A in Sertoli cells and male reproduction. Provide a reference for the toxicity of Bisphenol A to human reproduction.

Genome-wide identification, evolution, and expression of the SNARE gene family in wheat resistance to powdery mildew.

SNARE proteins mediate eukaryotic cell membrane/transport vesicle fusion and act in plant resistance to fungi. Herein, 173 SNARE proteins were identified in wheat and divided into 5 subfamilies and 21 classes. The number of the SYP1 class type was largest in TaSNAREs. Phylogenetic tree analysis revealed that most of the SNAREs were distributed in 21 classes. Analysis of the genetic structure revealed large differences among the 21 classes, and the structures in the same group were similar, except across individual genes. Excluding the first homoeologous group, the number in the other homoeologous groups was similar. The 2,000 bp promoter region of the TaSNARE genes were analyzed, and many W-box, MYB and disease-related cis-acting elements were identified. The qRT-PCR-based analysis of the SNARE genes revealed similar expression patterns of the same subfamily in one wheat variety. The expression patterns of the same gene in resistant/sensitive varieties largely differed at 6 h after infection, suggesting that SNARE proteins play an important role in early pathogen infection. Here, the identification and expression analysis of SNARE proteins provide a theoretical basis for studies of SNARE protein function and wheat resistance to powdery mildew.

FifBase: a comprehensive fertility-associated indicators factor database for domestic animals.

Fertility refers to the ability of animals to maintain reproductive function and give birth to offspring, which is an important indicator to measure the productivity of animals. Fertility is affected by many factors, among which environmental factors may also play key roles. During the past years, substantial research studies have been conducted to detect the factors related to fecundity, including genetic factors and environmental factors. However, the identified genes associated with fertility from countless previous studies are randomly dispersed in the literature, whereas some other novel fertility-related genes are needed to detect from omics-based datasets. Here, we constructed a fertility index factor database FifBase based on manually curated published literature and RNA-Seq datasets. During the construction of the literature group, we obtained 3301 articles related to fecundity for 13 species from PubMed, involving 2823 genes, which are related to 75 fecundity indicators or 47 environmental factors. Eventually, 1558 genes associated with fertility were filtered in 10 species, of which 1088 and 470 were from RNA-Seq datasets and text mining data, respectively, involving 2910 fertility-gene pairs and 58 fertility-environmental factors. All these data were cataloged into FifBase (http://www.nwsuaflmz.com/FifBase/), where the fertility-related factor information, including gene annotation and environmental factors, can be browsed, retrieved and downloaded with the user-friendly interface.

Characterization and Evaluation of Resistance to Powdery Mildew of Wheat-Aegilops geniculata Roth 7Mg (7A) Alien Disomic Substitution Line W16998.

Aegilops geniculata Roth has been used as a donor of disease-resistance genes, to enrich the gene pool for wheat (Triticum aestivum) improvement through distant hybridization. In this study, the wheat-Ae. geniculata alien disomic substitution line W16998 was obtained from the BC1F8 progeny of a cross between the common wheat 'Chinese Spring' (CS) and Ae. geniculata Roth (serial number: SY159//CS). This line was identified using cytogenetic techniques, analysis of genomic in situ hybridization (GISH), functional molecular markers (Expressed sequence tag-sequence-tagged site (EST-STS) and PCR-based landmark unique gene (PLUG), fluorescence in situ hybridization (FISH), sequential fluorescence in situ hybridization-genomic in situ hybridization (sequential FISH-GISH), and assessment of agronomic traits and powdery mildew resistance. During the anaphase of meiosis, these were evenly distributed on both sides of the equatorial plate, and they exhibited high cytological stability during the meiotic metaphase and anaphase. GISH analysis indicated that W16998 contained a pair of Ae. geniculata alien chromosomes and 40 common wheat chromosomes. One EST-STS marker and seven PLUG marker results showed that the introduced chromosomes of Ae. geniculata belonged to homoeologous group 7. Nullisomic-tetrasomic analyses suggested that the common wheat chromosome, 7A, was absent in W16998. FISH and sequential FISH-GISH analyses confirmed that the introduced Ae. geniculata chromosome was 7Mg. Therefore, W16998 was a wheat-Ae. geniculata 7Mg (7A) alien disomic substitution line. Inoculation of isolate E09 (Blumeria graminis f. sp. tritici) in the seedling stage showed that SY159 and W16998 were resistant to powdery mildew, indeed nearly immune, whereas CS was highly susceptible. Compared to CS, W16998 exhibited increased grain weight and more spikelets, and a greater number of superior agronomic traits. Consequently, W16998 was potentially useful. Germplasms transfer new disease-resistance genes and prominent agronomic traits into common wheat, giving the latter some fine properties for breeding.