Glutathione metabolism is conserved in response to excessive copper exposure between mice liver and Aurelia coerulea polyps.

BACKGROUND: Copper (Cu) is a trace element that is engaged in various routine physiological processes. Excessive copper exposure can cause damage to organisms; however, it is unknown if the mechanisms underlying the response to Cu2+ among different species are conserved. METHODS: Aurelia coerulea polyps and mice models were exposed to Cu2+ to assess its effects on survival status and organ damage. Transcriptomic sequencing, BLAST, structural analysis, and real-time quantitative PCR were carried out to analyze the similarities and differences in the molecular composition and response mechanisms between two species when exposed to Cu2+. RESULTS: Excessive Cu2+ exposure led to toxic effects on both A. coerulea polyps and mice. The polyps were injured at a Cu2+ concentration of 3.0 mg L-1. In the mice, increasing Cu2+ concentrations were correlated with, the degree of liver damage, which manifested as hepatocyte apoptosis. In the 300 mg L-1 Cu2+ group of mice, livers cell death was primarily triggered by the phagosome and Toll-like signaling pathways. We found the glutathione metabolism was significantly altered in response to copper stress in both A. coerulea polyps and mice. Moreover, the similarity of gene sequences enriched at the two same sites in this pathway was as high as 41.05 %-49.82 % and 43.61 %-45.99 % respectively. Among them, there was a conservative region in the structure of A. coerulea polyps GSTK1 and mice Gsta2, but the overall difference is large. CONCLUSION: Glutathione metabolism is a conserved copper response mechanism in evolutionary distant organisms such as A. coerulea polyps and mice, although mammals have a more complex regulatory network when it comes to copper-induced cell death.

Complete mitochondrial genome of Mastigias papua (Scyphozoa: Rhizostomeae: Mastigiidae) based on next-generation sequencing and phylogenetic analysis.

We assembled the complete mitochondrial genome (mitogenome) of Mastigias papua (Scyphozoa: Rhizostomeae: Mastigiidae) by the data generated from the next-generation sequencing platform. The complete mitogenome of M. papua was 16,560 bp in length, containing 14 protein-coding genes, two transfer RNA genes, and two ribosomal RNA genes. The base compositions were A 30.65%, C 15.16%, G 16.34%, and T 37.86%, with a gene arrangement similar to the mitogenomes derived from other representatives of Scyphozoa. Based on the 13 common protein-coding genes of 16 species within Scyphozoa, we constructed the phylogenetic tree and found that M. papua has a close relationship with Cassiopea andromeda and Cassiopea xamachana. All these species belong to an order of jellyfish Rhizostomeae, which have similar morphological characteristics. This is agreement with the conclusion we got by the phylogenetic relationship analysis using molecular data. This research has practical implications for advancing understanding of the phylogenetic relationships, taxonomic classifications, and phylogeography within Scyphozoa.

Integrated gene co-expression network analysis reveals unique developmental processes of Aurelia aurita.

The typical life cycle of the moon jellyfish (Aurelia aurita) includes the planula, polyp, strobila, ephyra, and medusa developmental stages. These stages exhibit huge differences in both external morphology and internal physiological functions. However, the gene co-expression network involved in these post-embryonic developmental processes has not been studied yet. Here, based on 15 RNA sequencing samples covering all five stages of the A. aurita life cycle, we systematically analyzed the gene co-expression network and obtained 35 relevant modules. Furthermore, we identified the highly correlated modules and hub genes for each stage. These hub genes are implicated to play important roles in the developmental processes of A. aurita, which should help improve our understanding of the jellyfish life cycle.

Next-generation sequencing yields the complete mitochondrial genome of Pterygoplichthys pardalis (Loricariidae; Siluriformes).

In this study, we report the complete mitochondrial genome of Pterygoplichthys pardalis has derived by next-generation sequencing. The complete mitochondrial genome of P. pardalis contains 16,425 bp encompassing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region (D-loop). The base composition is A 31.79%, C 26.89%, G 14.63%, and T 26.69%, and its gene arrangement is consistent with mitochondrial genomes derived from other representatives of Loricariidae. A phylogenetic tree of 24 Loricariidae species constructed based on the 13 coding genes shows that P. pardalis is clustered with other Pterygoplichthys genus. It suggests that the molecular classification results confirm its external morphological characteristics. These results have reference value for the further study of phylogenetic relationship, taxonomic classification, and phylogeography of Loricariidae.

A pair of long intergenic non-coding RNA LINC00887 variants act antagonistically to control Carbonic Anhydrase IX transcription upon hypoxia in tongue squamous carcinoma progression.

BACKGROUND: Long noncoding RNAs (lncRNAs) are important regulators in tumor progression. However, their biological functions and underlying mechanisms in hypoxia adaptation remain largely unclear. RESULTS: Here, we established a correlation between a Chr3q29-derived lncRNA gene and tongue squamous carcinoma (TSCC) by genome-wide analyses. Using RACE, we determined that two novel variants of this lncRNA gene are generated in TSCC, namely LINC00887_TSCC_short (887S) and LINC00887_TSCC_long (887L). RNA-sequencing in 887S or 887L loss-of-function cells identified their common downstream target as Carbonic Anhydrase IX (CA9), a gene known to be upregulated by hypoxia during tumor progression. Mechanistically, our results showed that the hypoxia-augmented 887S and constitutively expressed 887L functioned in opposite directions on tumor progression through the common target CA9. Upon normoxia, 887S and 887L interacted. Upon hypoxia, the two variants were separated. Each RNA recognized and bound to their responsive DNA cis-acting elements on CA9 promoter: 887L activated CA9's transcription through recruiting HIF1α, while 887S suppressed CA9 through DNMT1-mediated DNA methylation. CONCLUSIONS: We provided hypoxia-permitted functions of two antagonistic lncRNA variants to fine control the hypoxia adaptation through CA9.

Complete mitogenomes document substantial genetic contribution from the Eurasian Steppe into northern Pakistani Indo-Iranian speakers.

To elucidate whether Bronze Age population dispersals from the Eurasian Steppe to South Asia contributed to the gene pool of Indo-Iranian-speaking groups, we analyzed 19,568 mitochondrial DNA (mtDNA) sequences from northern Pakistani and surrounding populations, including 213 newly generated mitochondrial genomes (mitogenomes) from Iranian and Dardic groups, both speakers from the ancient Indo-Iranian branch in northern Pakistan. Our results showed that 23% of mtDNA lineages with west Eurasian origin arose in situ in northern Pakistan since ~5000 years ago (kya), a time depth very close to the documented Indo-European dispersals into South Asia during the Bronze Age. Together with ancient mitogenomes from western Eurasia since the Neolithic, we identified five haplogroups (~8.4% of maternal gene pool) with roots in the Steppe region and subbranches arising (age ~5-2 kya old) in northern Pakistan as genetic legacies of Indo-Iranian speakers. Some of these haplogroups, such as W3a1b that have been found in the ancient samples from the late Bronze Age to the Iron Age period individuals of Swat Valley northern Pakistan, even have sub-lineages (age ~4 kya old) in the southern subcontinent, consistent with the southward spread of Indo-Iranian languages. By showing that substantial genetic components of Indo-Iranian speakers in northern Pakistan can be traced to Bronze Age in the Steppe region, our study suggests a demographic link with the spread of Indo-Iranian languages, and further highlights the corridor role of northern Pakistan in the southward dispersal of Indo-Iranian-speaking groups.

High-continuity genome assembly of the jellyfish Chrysaora quinquecirrha.

The Atlantic sea nettle ( Chrysaora quinquecirrha) has an important evolutionary position due to its high ecological value. However, due to limited sequencing technologies and complex jellyfish genomic sequences, the current C. quinquecirrha genome assembly is highly fragmented. Here, we used the most advanced high-throughput chromosome conformation capture (Hi-C) technology to obtain high-coverage sequencing data of the C. quinquecirrha genome. We then anchored these data to the previously published contig-level assembly to improve the genome. Finally, a high-continuity genome sequence of C. quinquecirrha was successfully assembled, which contained 1 882 scaffolds with a N50 length of 3.83 Mb. The N50 length of the genome assembly was 5.23 times longer than the previously released one, and additional analysis revealed that it had a high degree of genomic continuity and accuracy. Acquisition of the high-continuity genome sequence of C. quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

High-Quality Genome Assembly of Chrysaora quinquecirrha Provides Insights Into the Adaptive Evolution of Jellyfish.

Jellyfish, such as Chrysaora quinquecirrha, hold an important evolutionary position and have great ecological value. However, limited genomic resources are currently available for studying their basic genetic and development processes. Here, we de novo assembled the first high-quality reference genome of C. quinquecirrha, and successfully annotated 21,606 protein-coding genes. Codon usage analysis identified the frequent use of low-GC-content codons during protein-coding gene translation. Analysis of the relative evolution rate indicated that jellyfish had a faster evolution rate than sea anemones but slower rate than the species in Hydra. Phylogenetic analysis with two other species of jellyfish indicated that Aurelia aurita and Nemopilema nomurai have a closer relationship with each other than with C. quinquecirrha, with divergence from their common ancestor occurring ≈475.7 million years ago. Our study not only showed the genomic characteristics and molecular adaptive evolution of C. quinquecirrha, but also provides valuable genomic resources for further study on complex developmental processes and environmental adaptations.

Glycerophosphodiester phosphodiesterase 1 (GDE1) acts as a potential tumor suppressor and is a novel therapeutic target for non-mucin-producing colon adenocarcinoma.

Colon adenocarcinoma (COAD) represents a major public health issue due to its high incidence and mortality. As different histological subtypes of COAD are related to various survival outcomes and different therapies, finding specific targets and treatments for different subtypes is one of the major demands of individual disease therapy. Interestingly, as these different subtypes show distinct metabolic profiles, it may be possible to find specific targets related to histological typing by targeting COAD metabolism. In this study, the differential expression patterns of metabolism-related genes between COAD (n = 289) and adjacent normal tissue (n = 41) were analyzed by one-way ANOVA. We then used weighted gene co-expression network analysis (WGCNA) to further identify metabolism-related gene connections. To determine the critical genes related to COAD metabolism, we obtained 2,114 significantly differentially expressed genes (DEGs) and 12 modules. Among them, we found the hub module to be significantly associated with histological typing, including non-mucin-producing colon adenocarcinoma and mucin-producing colon adenocarcinoma. Combining survival analysis, we identified glycerophosphodiester phosphodiesterase 1 (GDE1) as the most significant gene associated with histological typing and prognosis. This gene displayed significantly lower expression in COAD compared with normal tissues and was significantly correlated with the prognosis of non-mucin-producing colon adenocarcinoma (p = 0.0017). Taken together, our study showed that GDE1 exhibits considerable potential as a novel therapeutic target for non-mucin-producing colon adenocarcinoma.

Weighted Gene Co-Expression Network Analysis Reveals Six Hub Genes Involved in and Tight Junction Function in Pancreatic Adenocarcinoma and their Potential Use in Prognosis.

Background: Pancreatic adenocarcinoma (PAAD) is an aggressive and invasive tumor with poor prognosis. Identifying prognostic biomarkers of PAAD will provide crucial information for developing treatment plans. Methods: In this analysis, a gene-expression dataset, containing RNA-sequencing data recalculated into transcripts per million, was obtained from the UCSC Xena platform. Three thousand nine hundred and seventy six differentially expressed genes were obtained with analysis of variance. Using these data a co-expression network was constructed using weighted gene co-expression network analysis, from which we obtained eight modules. Results: The blue module included 497 genes and demonstrated significant negative correlation with overall survival. Furthermore, pathway analyses demonstrated the involvement of many of these genes in the tight junction pathway, which plays a critical role in PAAD. In addition, we identified six genes in common (i.e., ANXA2 [annexin A2], EPHA2 [erythropoietin-producing hepatocellular class A2], ITGB4 [integrin beta 4], KRT19 [keratin type I cytoskeletal 19], LGALS3 [galectin-3], and S100A14 [S100 calcium binding protein A14]) between the protein-protein interaction and gene co-expression networks that may have critical functions in PAAD. These hub genes were not only highly expressed at the RNA level but also exhibited high expression in the immunohistological data in the Human Protein Atlas Database. Conclusion: Thus, this research clarified the framework of co-expressed gene modules in PAAD and highlighted potential prognostic biomarkers for the clinical diagnosis of PAAD.

Identification of four hub genes associated with adrenocortical carcinoma progression by WGCNA.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignant cancer in the adrenal cortex with poor prognosis. Though previous research has attempted to elucidate the progression of ACC, its molecular mechanism remains poorly understood. METHODS: Gene transcripts per million (TPM) data were downloaded from the UCSC Xena database, which included ACC (The Cancer Genome Atlas, n = 77) and normal samples (Genotype Tissue Expression, n = 128). We used weighted gene co-expression network analysis to identify gene connections. Overall survival (OS) was determined using the univariate Cox model. A protein-protein interaction (PPI) network was constructed by the search tool for the retrieval of interacting genes. RESULTS: To determine the critical genes involved in ACC progression, we obtained 2,953 significantly differentially expressed genes and nine modules. Among them, the blue module demonstrated significant correlation with the "Stage" of ACC. Enrichment analysis revealed that genes in the blue module were mainly enriched in cell division, cell cycle, and DNA replication. Combined with the PPI and co-expression networks, we identified four hub genes (i.e., TOP2A, TTK, CHEK1, and CENPA) that were highly expressed in ACC and negatively correlated with OS. Thus, these identified genes may play important roles in the progression of ACC and serve as potential biomarkers for future diagnosis.