Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Янв. 24, 2023

Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one the limited therapies available. However, only subgroup uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode vascularization specific histopathological growth patterns (HGPs), which have proven prognostic predictive significance. Nevertheless, molecular mechanisms poorly understood.We evaluated CRCLM from 225 patients regarding HGP clinical data. Moreover, we performed spatial (21,804 spots) single-cell (22,419 cells) RNA sequencing analyses explore differences in detail, further validated vitro immunohistochemical analysis patient-derived organoid cultures.We detected metabolic alterations signature WNT signalling activation metastatic cells related VCO phenotype. Importantly, corresponding healthy displaying angiogenesis, identified predominantly expressed capillary subtype endothelial cells, could be explored as possible predictor for relying angiogenesis.These findings may prove novel therapeutic targets treatment CRCLM, special ones VCO.

Язык: Английский

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Whole transcriptome analysis to identify non-coding RNA regulators and hub genes in sperm of non-obstructive azoospermia by microarray, single-cell RNA sequencing, weighted gene co-expression network analysis, and mRNA-miRNA-lncRNA interaction analysis

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Июнь 11, 2024

Abstract Background The issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation non-coding RNA (ncRNA), crucial for sperm development, are significant factors. This gene can affect motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in differentiation development vital. knowledge could lead more effective treatments interventions infertility. Materials methods Our research aim identify new key genes ncRNA involved non-obstructive azoospermia (NOA), improving diagnosis offering accurate estimates successful extraction based on an individual’s genotype. Results We analyzed transcript three NOA patients who tested negative issues, employing comprehensive genome-wide analysis approximately 50,000 sequences using microarray technology. compared profiles between normal sperm. found differences: 150 were up-regulated, 78 down-regulated, along with 24 ncRNAs up-regulated 13 down-regulated conditions. By cross-referencing our results a single-cell genomics database, we identified overexpressed biological process terms differentially expressed genes, such as “protein localization endosomes” “xenobiotic transport.” Overrepresented molecular function included “voltage-gated calcium channel activity,” “growth hormone-releasing hormone receptor “sialic acid transmembrane transporter activity.” Analysis revealed nine hub associated sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1 , VPS36 . Conclusions These their interacting proteins may role pathophysiology germ cell abnormalities

Язык: Английский

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Whole Exome Sequencing and In Silico Analysis of Human Sertoli in Patients with Non-Obstructive Azoospermia

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(20), С. 12570 - 12570

Опубликована: Окт. 20, 2022

Non-obstructive azoospermia (NOA) is a serious cause of male infertility. The Sertoli cell responds to androgens and takes on roles supporting spermatogenesis, which may This work aims enhance the genetic diagnosis NOA via discovery new hub genes implicated in human better assess odds successful sperm extraction according individual's genotype. Whole exome sequencing (WES) was done three patients find key involved NOA. We evaluated genome-wide transcripts (about 50,000 transcripts) by microarray between non-obstructive normal cells. analysis cases with different revealed that 32 were upregulated, expressions 113 downregulated versus case. For this purpose, Enrich Shiny GO, STRING, Cytoscape online evaluations applied predict functional molecular interactions proteins then recognize master pathways. enrichment demonstrated biological process (BP) terms "inositol lipid-mediated signaling", "positive regulation transcription RNA polymerase II", DNA-templated transcription" significantly changed upregulated differentially expressed (DEGs). BP investigation DEGs highlighted "mitotic cytokinesis", "regulation protein-containing complex assembly", "cytoskeleton-dependent "peptide metabolic process". Overrepresented function (MF) included "ubiquitin-specific protease binding", "protease "phosphatidylinositol trisphosphate phosphatase activity", "clathrin light chain binding". Interestingly, MF overexpression "ATPase inhibitor "glutathione transferase regulator activity". Our findings suggest these their interacting could help determine pathophysiologies germ abnormalities

Язык: Английский

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Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer

iScience, Год журнала: 2023, Номер 26(11), С. 108218 - 108218

Опубликована: Окт. 17, 2023

Triple-negative breast cancer (TNBC) poses a considerable challenge due to its aggressive nature. Notably, metal ion-induced cell death, such as ferroptosis, has garnered significant attention and demonstrated potential implications for cancer. Recently, cuproptosis, potent death pathway reliant on copper, been identified. However, whether cuproptosis can be targeted treatment remains uncertain. Here, we screened the US Food Drug Administration (FDA)-approved drug library identified zinc pyrithione (ZnPT) compound that significantly inhibited TNBC progression. RNA sequencing revealed ZnPT disrupted copper homeostasis. Furthermore, facilitated oligomerization of dihydrolipoamide S-acetyltransferase, landmark molecule cuproptosis. Clinically, high expression levels cuproptosis-related proteins were correlated with poor prognosis in patients. Collectively, these findings indicate induce by targeting disrupting homeostasis, providing experimental foundation exploring target discovery

Язык: Английский

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OCT4 protein and gene expression analysis in the differentiation of spermatogonia stem cells into neurons by immunohistochemistry, immunocytochemistry, and bioinformatics analysis

Stem Cell Reviews and Reports, Год журнала: 2023, Номер 19(6), С. 1828 - 1844

Опубликована: Апрель 29, 2023

Язык: Английский

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Microarray and in silico analysis of DNA repair genes between human testis of patients with nonobstructive azoospermia and normal cells

Cell Biochemistry and Function, Год журнала: 2022, Номер 40(8), С. 865 - 879

Опубликована: Сен. 19, 2022

Abstract DNA repair processes are critical to maintaining genomic integrity. As a result, dysregulation of genes is likely be linked with health implications, such as an increased prevalence infertility and accelerated rate aging. We evaluated all the (322 genes) by microarray. This study has provided insight into connection between genes, including RAD23B, OBFC2A, PMS1, UBE2V1, ERCC5, SMUG1, RFC4, PMS2L5, MMS19, SHFM1, INO80, PMS2L1, CHEK2, TRIP13 , POLD4 . The microarray analysis six human cases different nonobstructive azoospermia revealed that SHFM1 INO80 were upregulated, expression was downregulated versus normal case. For this purpose, Enrich Shiny GO, STRING, Cytoscape online evaluation applied predict proteins’ functional molecular interactions then performed recognize master pathways. Functional enrichment biological process (BP) terms “base‐excision repair, AP site formation,” “nucleotide‐excision gap filling,” preincision complex assembly” significantly overexpressed in upregulated differentially expressed (DEGs). BP DEGs highlighted “histone phosphorylation,” “DNA damage response, detection response,” “mitotic cell cycle checkpoint signaling,“ “double‐strand break repair.” Overrepresented function (MF) included “Oxidized base lesion N ‐glycosylase activity,” “uracil “bubble binding” clamp loader activity.” Interestingly, MF investigation showed overexpression “heterotrimeric G‐protein complex,” “5′‐deoxyribose‐5‐phosphate lyase “minor groove adenine‐thymine‐rich binding,” kinase Our findings suggest these their interacting hub proteins could help determine pathophysiology germ abnormalities infertility.

Язык: Английский

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Altered G-Protein Transduction Protein Gene Expression in the Testis of Infertile Patients with Nonobstructive Azoospermia

DNA and Cell Biology, Год журнала: 2023, Номер 42(10), С. 617 - 637

Опубликована: Авг. 23, 2023

Recent studies have shown that several members of the G-protein-coupled receptors (GPCR) superfamily play crucial roles in maintenance ion-water homeostasis sperm and Sertoli cells, development germ formation blood barrier, maturation sperm. The GPCR, guanyl-nucleotide exchange factor, membrane traffic protein, small GTPase genes were analyzed by microarray bioinformatics (3513 cell genes). In analyses three human cases with different nonobstructive azoospermia sperm, expression GOLGA8IP, OR2AT4, PHKA1, A2M, OR56A1, SEMA3G, LRRC17, APP, ARHGAP33, RABGEF1, NPY2R, GHRHR, LTB4R2, GRIK5, OR6K6, NAPG, OR6C65, VPS35, FPR3, ARL4A was upregulated, while MARS, SIRPG, OGFR, GPR150, LRRK1, NGEF downregulated. There an increase GBP3, TNF, TGFB3, CLTC cells NOA, whereas PAQR4, RRAGD, RAC2, SERPINB8, IRPB1, MRGPRF, RASA2, RGS2, RAP2A, RAB2B, ARL17, SERINC4, XIAP, DENND4C, ANKRA2, CSTA, STX18, SNAP23 A combined analysis Enrich Shiny Gene Ontology (GO), STRING, Cytoscape used to predict proteins' molecular interactions then recognize master pathways. Functional enrichment showed biological process (BP), regulation protein metabolic process, GTPase-mediated signal transduction significantly expressed up-/downregulated differentially (DEGs) function (MF) experiments DEGs up-/downregulated, it found GPCR activity, guanyl ribonucleotide binding, activity nucleoside-triphosphatase overexpressed. An GO findings BP MF be common DEGs. When these gene mutations been validated, they can create new antagonists or agonists are receptor-selective.

Язык: Английский

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Differential expression of ion channel coding genes in the endometrium of women experiencing recurrent implantation failures

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 27, 2024

Our study probed the differences in ion channel gene expression endometrium of women with Recurrent Implantation Failure (RIF) compared to fertile women. We analyzed relative genes coding for T-type Ca2+, ENaC, CFTR, and KCNQ1 channels endometrial samples from 20 RIF-affected 10 control women, aged 22-35, via microarray analysis quantitative real-time PCR. Additionally, we examined DNA methylation regulatory region using ChIP The bioinformatics component our research included Gene Ontology analysis, protein-protein interaction networks, signaling pathway mapping identify key biological processes pathways implicated RIF. This led discovery significant alterations RIF women's endometrium, most notably an overexpression CFTR reduced SCNN1A, SCNN1B, SCNN1G, CACNA1H, KCNQ1. A higher level KCNQ1's was also observed patients. Gene-set enrichment highlighted a presence involved transport membrane potential regulation, particularly sodium calcium complexes, which are vital cation movement across cell membranes. Genes were enriched broader transmembrane transporter underscoring their extensive role cellular homeostasis signaling. These findings suggest involvement pathology implantation failure, offering new insights into mechanisms behind possible therapeutic targets.

Язык: Английский

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The Role of Vimentin in Human Corneal Fibroblast Spreading and Myofibroblast Transformation

Cells, Год журнала: 2024, Номер 13(13), С. 1094 - 1094

Опубликована: Июнь 25, 2024

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, cell-matrix adhesion, and fibrotic transformation. Here, we assess how vimentin impacts morphology, myofibroblast transformation of human corneal fibroblasts. Overall, although knockout (KO) did not dramatically impact fibroblast spreading mechanical activity (traction force), elongation response PDGF was reduced KO cells compared controls. Blocking polymerization using Withaferin had even more pronounced effects on also inhibited cell-induced matrix contraction. Furthermore, absence completely block TGFβ-induced transformation, the degree amount αSMA protein expression reduced. Proteomics showed that cultured TGFβ a similar pattern One exception included periostin, an ECM associated with wound healing fibrosis other types, which highly expressed only Vim cells. We demonstrate for first time LRRC15, previously cancer-associated fibroblasts, is by myofibroblasts. Interestingly, proteins LRRC15 collagen, fibronectin, β1 integrin α11 integrin, were upregulated. our data show both identified novel may regulate presence and/or vimentin.

Язык: Английский

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Research Progress of Vimentin in Viral Infections

Antiviral Research, Год журнала: 2025, Номер unknown, С. 106121 - 106121

Опубликована: Фев. 1, 2025

Язык: Английский

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