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Biomolecules & Biomedicine Jun 2024Colorectal cancer (CRC) is one of the most common non-cutaneous malignancies, causing significant mortality and a substantial burden. This study aims to explore the role...
Colorectal cancer (CRC) is one of the most common non-cutaneous malignancies, causing significant mortality and a substantial burden. This study aims to explore the role of KIAA1429 (also known as vir-like m6A methyltransferase associated [VIRMA]) protein in the radioresistance of CRC. CRC cells and a radioresistant cell line were cultured, and KIAA1429 expression was detected. After the down-regulation of KIAA1429, its effect on the radioresistance and ferroptosis of cancer cells was analyzed. The role of ferroptosis in radioresistance was verified. The binding relationship among long non-coding RNA endogenous Bornavirus-like nucleoprotein 3, pseudogene (lncRNA EBLN3P), microRNA (miR)-153-3p, and KIAA1429 was analyzed. KIAA1429 and lncRNA EBLN3P were highly expressed in CRC, while miR-153-3p was poorly expressed. KIAA1429 and lncRNA EBLN3P were further increased/decreased in the radioresistant cells. KIAA1429 knockdown decreased the survival rate of the radioresistant cell line after X-ray irradiation and increased gamma H2A histone family member X (γ-H2AX), ferroptosis, and oxidative stress. A ferroptosis inhibitor alleviated the inhibitory effect of KIAA1429 knockdown on radioresistance. KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P, and lncRNA EBLN3P increased KIAA1429 by competitively binding to miR-153-3p. miR-153-3p silencing or lncRNA EBLN3P overexpression attenuated the promotion of ferroptosis and the inhibition of radioresistance induced by KIAA1429 knockdown. Overall, KIAA1429-mediated m6A modification up-regulated lncRNA EBLN3P expression, and lncRNA EBLN3P increased KIAA1429 expression by competitively binding to miR-153-3p, thus reducing ferroptosis and increasing the radioresistance of CRC.
PubMed: 38843497
DOI: 10.17305/bb.2024.10313 -
American Journal of Physiology.... Jun 2024Na/Cl cotransporter 2 (Ncc2 or Slc12a10), is a membrane transport protein that belongs to the electroneutral cation-chloride cotransporter family. The Slc12a10 gene ()...
Na/Cl cotransporter 2 (Ncc2 or Slc12a10), is a membrane transport protein that belongs to the electroneutral cation-chloride cotransporter family. The Slc12a10 gene () is widely present in bony vertebrates but is deleted or pseudogenized in birds, some bony fishes, and most mammals. Slc12a10 is highly homologous to Ncc (Slc12a3 or Ncc1); however, there are only a few reports measuring the activity of Slc12a10. In this study, we focused on zebrafish Slc12a10.1 (zSlc12a10.1) and analyzed its activity using oocyte electrophysiology. Analysis using Na-selective microelectrodes showed that intracellular sodium activity (Na) in zSlc12a10.1 oocytes was significantly decreased in Na- or Cl-free medium and recovered when Na or Cl was readded to the medium. Similar analysis using a Cl-selective microelectrode showed that intracellular chloride activity (Cl) in zSlc12a10.1 oocytes significantly decreased in Na- or Cl-free medium and recovered when Na or Cl was readded to the medium. When a similar experiment was performed with a voltage clamp, the membrane current did not change when Na of zSlc12a10.1 oocytes were decreased in Na-free medium. Molecular phylogenetic and synteny analyses suggest that gene duplication between and in zebrafish, is a relatively recent event, whereas gene duplication between and the ancestral gene of / occurred at least about 2 million years ago. deficiency was observed in species belonging to Ictaluridae, Salmoniformes, Osmeriformes, Batrachoididae, Syngnathiformes, Gobiesociformes, Labriformes, and Tetraodontiformes. These results indicate that zebrafish Slc12a10.1 is an electroneutral Na/Clcotransporter and establish its evolutionary position among various teleost paralogs.
PubMed: 38842519
DOI: 10.1152/ajpregu.00096.2024 -
Cell Cycle (Georgetown, Tex.) Jun 2024Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with...
Bladder cancer (BC) is one of the most common malignant neoplasms worldwide. Competing endogenous RNA (ceRNA) networks may identify potential biomarkers associated with the progression and prognosis of BC. The OCT4-pg5/miR-145-5p/OCT4B ceRNA network was found to be related to the progression and prognosis of BC. OCT4-pg5 expression was significantly higher in BC cell lines than in normal bladder cells, with OCT4-pg5 expression correlating with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, whereas miR-145-5p suppressed these activities. The 3' untranslated region (3'UTR) of OCT4-pg5 competed for miR-145-5p, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted epithelial-mesenchymal transition (EMT) by activating the Wnt/β-catenin pathway and upregulating the expression of matrix metalloproteinases (MMPs) 2 and 9 as well as the transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. The OCT4-pg5/miR-145-5p/OCT4B axis promotes the progression of BC by inducing EMT via the Wnt/β-catenin pathway and enhances cisplatin resistance. This axis may represent a therapeutic target in patients with BC.
PubMed: 38842275
DOI: 10.1080/15384101.2024.2353554 -
Nature Genetics Jun 2024Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis of pathogen evolution....
Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis of pathogen evolution. Although the genomes of numerous Salmonella isolates with broad variations in host range and human disease manifestations have been sequenced, the functional links between genetic and phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput functional genomics on both generalist (Typhimurium) and human-restricted (Typhi and Paratyphi A) Salmonella at unprecedented scale in the study of this enteric pathogen. Using a comprehensive systems biology approach, we identify gene networks with serovar-specific fitness effects across 25 host-associated stresses encountered at key stages of human infection. By experimentally perturbing these networks, we characterize previously undescribed pseudogenes in human-adapted Salmonella. Overall, this work highlights specific vulnerabilities encoded within human-restricted Salmonella that are linked to the degradation of their genomes, shedding light into the evolution of this enteric pathogen.
Topics: Humans; Salmonella Infections; Genetic Fitness; Genome, Bacterial; Stress, Physiological; Gene Regulatory Networks; Salmonella; Pseudogenes; Host-Pathogen Interactions
PubMed: 38831009
DOI: 10.1038/s41588-024-01779-7 -
Physiological Reports Jun 2024Solute carrier family 26 (Slc26) is a family of anion exchangers with 11 members in mammals (named Slc26a1-a11). Here, we identified a novel member of the slc26 family,...
Solute carrier family 26 (Slc26) is a family of anion exchangers with 11 members in mammals (named Slc26a1-a11). Here, we identified a novel member of the slc26 family, slc26a12, located in tandem with slc26a2 in the genomes of several vertebrate lineages. BLAST and synteny analyses of various jawed vertebrate genome databases revealed that slc26a12 is present in coelacanths, amphibians, reptiles, and birds but not in cartilaginous fishes, lungfish, mammals, or ray-finned fishes. In some avian and reptilian lineages such as owls, penguins, egrets, and ducks, and most turtles examined, slc26a12 was lost or pseudogenized. Phylogenetic analysis showed that Slc26a12 formed an independent branch with the other Slc26 members and Slc26a12, Slc26a1 and Slc26a2 formed a single branch, suggesting that these three members formed a subfamily in Slc26. In jawless fish, hagfish have two genes homologous to slc26a2 and slc26a12, whereas lamprey has a single gene homologous to slc26a2. African clawed frogs express slc26a12 in larval gills, skin, and fins. These results show that slc26a12 was present at least before the separation of lobe-finned fish and tetrapods; the name slc26a12 is appropriate because the gene duplication occurred in the distant past.
Topics: Animals; Phylogeny; Reptiles; Sulfate Transporters; Amphibians; Birds; Evolution, Molecular
PubMed: 38828713
DOI: 10.14814/phy2.16089 -
The Biological Bulletin Aug 2023AbstractWe describe the cloning and expression of a nonreceptor tyrosine kinase, (), a () gene, identified in a subtractive screen for maternal ascidian cDNAs in , an...
AbstractWe describe the cloning and expression of a nonreceptor tyrosine kinase, (), a () gene, identified in a subtractive screen for maternal ascidian cDNAs in , an ascidian species with a tadpole larva. The gene encodes a 4-kb mRNA expressed in gonads, eggs, and embryos in the tailed but is not detected in eggs or embryos of the closely related tailless species . There is a large insertion in in the genome, as shown by transcriptome and genome analyses, resulting in it becoming a pseudogene. The amino acid sequence encodes a nonreceptor tyrosine kinase with an N-terminal region containing two SH2 domains and five ankyrin repeats, similar to the gene found in other ascidians. Thus, the ascidian genes are members of the SHARK (Src-homology ankyrin-repeat containing tyrosine kinase) family of nonreceptor tyrosine kinases, which are found throughout invertebrates and missing from vertebrates. We show that is lacking the tyrosine kinase domain in the tailless , although the truncated mRNA is still expressed in transcriptome data. This maternal and zygotic tyrosine kinase is another described pseudogene from and appears not to be necessary for adult development.
Topics: Animals; Urochordata; Protein-Tyrosine Kinases; Amino Acid Sequence; Zygote; Pseudogenes; Phylogeny
PubMed: 38820291
DOI: 10.1086/730536 -
BMC Genomic Data May 2024Oreomecon nudicaulis, commonly known as mountain poppy, is a significant perennial herb. In 2022, the species O. nudicaulis, which was previously classified under the...
Oreomecon nudicaulis, commonly known as mountain poppy, is a significant perennial herb. In 2022, the species O. nudicaulis, which was previously classified under the genus Papaver, was reclassified within the genus Oreomecon. Nevertheless, the phylogenetic status and chloroplast genome within the genus Oreomecon have not yet been reported. This study elucidates the chloroplast genome sequence and structural features of O. nudicaulis and explores its evolutionary relationships within Papaveraceae. Using Illumina sequencing technology, the chloroplast genome of O. nudicaulis was sequenced, assembled, and annotated. The results indicate that the chloroplast genome of O. nudicaulis exhibits a typical circular quadripartite structure. The chloroplast genome is 153,903 bp in length, with a GC content of 38.87%, containing 84 protein-coding genes, 8 rRNA genes, 38 tRNA genes, and 2 pseudogenes. The genome encodes 25,815 codons, with leucine (Leu) being the most abundant codon, and the most frequently used codon is AUU. Additionally, 129 microsatellite markers were identified, with mononucleotide repeats being the most abundant (53.49%). Our phylogenetic analysis revealed that O. nudicaulis has a relatively close relationship with the genus Meconopsis within the Papaveraceae family. The phylogenetic analysis supported the taxonomic status of O. nudicaulis, as it did not form a clade with other Papaver species, consistent with the revised taxonomy of Papaveraceae. This is the first report of a phylogenomic study of the complete chloroplast genome in the genus Oreomecon, which is a significant genus worldwide. This analysis of the O. nudicaulis chloroplast genome provides a theoretical basis for research on genetic diversity, molecular marker development, and species identification, enriching genetic information and supporting the evolutionary relationships among Papaveraceae.
Topics: Phylogeny; Genome, Chloroplast; Genomics; Papaveraceae; Microsatellite Repeats; Chloroplasts; Base Composition; Evolution, Molecular; RNA, Transfer
PubMed: 38816818
DOI: 10.1186/s12863-024-01236-8 -
Turkish Journal of Medical Sciences 2024Chemical biological radiological nuclear threats are at an important point in the agenda of world health today, as they can cause mass deaths. attracts attention as a...
BACKGROUND/AIM
Chemical biological radiological nuclear threats are at an important point in the agenda of world health today, as they can cause mass deaths. attracts attention as a potential biological warfare agent due to its features such as multidrug resistance, a rapid transmission mechanism via aerosol, the absence of a complete treatment protocol for the infection it causes, and the absence of an approved vaccine for protection against the bacteria. suspect samples must be studied by experienced personnel in biosafety level III laboratories. is a difficult and troublesome pathogen to diagnose and many unknowns about today. Therefore, the aim of the study was to determine the molecular differences and potential resistance genes of strains.
MATERIALS AND METHODS
Determination of the molecular differences and potential resistance genes of strains with new bioinformatics approaches by comparatively examining the data of 29 B mallei strains, 10 of which were isolated from Türkiye, on the genome list of the National Biotechnology Information Center (NCBI).
RESULTS
According to the genome annotations of the origins, the origin containing the highest number of CDS which is 5172 was found as the 11th strain obtained in Türkiye in 1949. The origin with the highest number of pseudogenes was determined as 23,344 (China 7) origin. Two hundred and eighty-five pseudogenes found in this strain were obtained from a knee effusion in Myanmar. According to chromosome 2 data, strain was determined as the most similar strain to ATCC 23344, line 11 with NCTC 10229 strain, and SAVP1 strain was determined as the least similar strain. When the antimicrobial resistance gene markers of the isolates included in the study were examined, , were found to be carrying.
CONCLUSION
In terms of public health, it was thought that the data obtained as a result of our study about , which is defined as a biological weapon, is very valuable for creating treatment protocols to be applied to possible epidemics in the future. In addition, the available genetic epidemiological data of these strains belonging to a category that is dangerous to work with in a laboratory environment were reviewed.
Topics: Burkholderia mallei; Humans; Drug Resistance, Bacterial; Turkey
PubMed: 38812620
DOI: 10.55730/1300-0144.5761 -
NPJ Genomic Medicine May 2024Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal dysplasia that primarily affects females. The only known causative gene is IKBKG, and the most...
Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal dysplasia that primarily affects females. The only known causative gene is IKBKG, and the most common genetic cause is the recurrent IKBKG deletion resulting from recombination between two MER67B repeats. Detection of variants in IKBKG is challenging due to the presence of a highly homologous non-pathogenic pseudogene IKBKGP1. In this study, we successfully identified four pathogenic variants in four IP patients using a strategy based on single-tube long fragment read (stLFR) sequencing with a specialized analysis pipeline. Three frameshift variants (c.519-3_519dupCAGG, c.1167dupC, and c.700dupT) were identified and subsequently validated by Sanger sequencing. Notably, c.519-3_519dupCAGG was found in both IKBKG and IKBKGP1, whereas the other two variants were only detected in the functional gene. The IKBKG deletion was identified and confirmed in one patient. These results demonstrate that the proposed strategy can identify potential pathogenic variants and distinguish whether they are derived from IKBKG or its pseudogene. Thus, this strategy can be an efficient genetic testing method for IKBKG. By providing a comprehensive understanding of the whole genome, it may also enable the exploration of other genes potentially associated with IP. Furthermore, the strategy may also provide insights into other diseases with detection challenges due to pseudogenes.
PubMed: 38811629
DOI: 10.1038/s41525-024-00421-z -
Proceedings of the National Academy of... Jun 2024In many mammals, recombination events are concentrated in hotspots directed by a sequence-specific DNA-binding protein named PRDM9. Intriguingly, PRDM9 has been lost...
In many mammals, recombination events are concentrated in hotspots directed by a sequence-specific DNA-binding protein named PRDM9. Intriguingly, PRDM9 has been lost several times in vertebrates, and notably among mammals, it has been pseudogenized in the ancestor of canids. In the absence of PRDM9, recombination hotspots tend to occur in promoter-like features such as CpG islands. It has thus been proposed that one role of PRDM9 could be to direct recombination away from PRDM9-independent hotspots. However, the ability of PRDM9 to direct recombination hotspots has been assessed in only a handful of species, and a clear picture of how much recombination occurs outside of PRDM9-directed hotspots in mammals is still lacking. In this study, we derived an estimator of past recombination activity based on signatures of GC-biased gene conversion in substitution patterns. We quantified recombination activity in PRDM9-independent hotspots in 52 species of boreoeutherian mammals. We observe a wide range of recombination rates at these loci: several species (such as mice, humans, some felids, or cetaceans) show a deficit of recombination, while a majority of mammals display a clear peak of recombination. Our results demonstrate that PRDM9-directed and PRDM9-independent hotspots can coexist in mammals and that their coexistence appears to be the rule rather than the exception. Additionally, we show that the location of PRDM9-independent hotspots is relatively more stable than that of PRDM9-directed hotspots, but that PRDM9-independent hotspots nevertheless evolve slowly in concert with DNA hypomethylation.
Topics: Animals; Histone-Lysine N-Methyltransferase; Recombination, Genetic; Humans; Mammals; CpG Islands; Eutheria; Mice; Female; Gene Conversion; Evolution, Molecular
PubMed: 38809707
DOI: 10.1073/pnas.2401973121