Cellular landscape of adrenocortical carcinoma at single-nuclei resolution DOI Open Access
David S. Tourigny, Barbara Altieri, Kerim Secener

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 11, 2023

Abstract Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with molecular pathology that remain incompletely understood. To gain novel insights into cellular landscape ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC samples and analysed these alongside previously published snRNA-seq set normal glands (NAGs). We find microenvironment to be relatively devoid immune cells compared NAG tissues, consistent known high purity values for as an immunologically “cold” tumour. Our analysis identifies three separate groups are characterised by different relative compositions adrenocortical cell types, including two populations (ACC 1 2) specifically enriched in most aggressive tumours display hallmarks epithelial mesenchymal transition (EMT) dysregulated steroidogenesis, respectively. In addition types associated hypoxic metabolic signatures 3 4) prevalent among less-aggressive tumours, also identified validated population mitotically active M) strongly overexpressing genes POLQ DIAPH3 possibly supports expansion malignant lineages. The smallest specific type, 5, displays characteristics increased proliferation growth factor signalling, therefore potential progenitor-like or cell-of-origin candidate lineages involved carcinogenesis. Intriguingly, linage tracing suggests fate adopted upon differentiation appears at least partly copy number allelic balance state imprinted DLK1 / MEG3 genomic locus, which verified assessing DNA methylation status defined their type compositions. results provide new heterogeneity indicating genetic perturbations hierarchical mechanism underlying healthy renewal zonation may explain basis disease pathogenesis.

Language: Английский

Cellular landscape of adrenocortical carcinoma at single-nuclei resolution DOI Creative Commons
David S. Tourigny, Barbara Altieri, Kerim Secener

et al.

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 590, P. 112272 - 112272

Published: May 15, 2024

Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with molecular pathology that remains incompletely understood. To gain novel insights into cellular landscape ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC samples and analysed these alongside snRNA-seq normal glands (NAGs). We find microenvironment to be relatively devoid immune cells compared NAG tissues, consistent known high purity values for as an immunologically "cold" tumour. Our analysis identifies three separate groups are characterised by different relative compositions adrenocortical cell types. These include populations specifically enriched in most clinically aggressive hormonally active tumours, displaying hallmarks reorganised mechanobiology dysregulated steroidogenesis, respectively. also identified validated population mitotically strongly overexpress genes POLQ, DIAPH3 EZH2 support expansion LGR4+ progenitor-like or cell-of-origin candidate carcinogenesis. Trajectory inference suggests fate adopted malignant upon differentiation associated copy number allelic balance state imprinted DLK1/MEG3 genomic locus, which verified assessing bulk DNA methylation status. In conclusion, our results therefore provide new clinical heterogeneity revealing how genetic perturbations healthy renewal zonation basis disease pathogenesis.

Language: Английский

Citations

4
CircDIAPH1 Promotes Liver Metastasis and Development of Colorectal Cancer by Initiation of CEACAM6 Expression DOI Open Access
Wei Wang, Xu Li, Hantao Wang

et al.

Molecular Carcinogenesis, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

ABSTRACT Liver metastasis is a critical factor influencing the 5‐year survival rate in colorectal cancer (CRC). However, biological function of most circRNAs liver CRC still unknown. In this study, we identified differentially expressed associated with (LM‐DE‐circRNAs). A total 247 LM‐DE‐circRNAs were identified, and crucial signaling pathways, including regulation actin cytoskeleton, significantly enriched, featuring six LM‐DE‐circRNAs. Notably, circDIAPH1 (hsa_circ_0074323), highest AUC value, emerged as potential biomarker for (CRLM). Functional assays following knockdown demonstrated induced apoptosis, suppressed proliferation, reduced metastasis, invasion cell lines vitro. The attenuated tumor growth cell‐derived xenograft model. Furthermore, lessened metastasis. Transcriptome profiling revealed that CEACAM6 was downregulated gene while knocked down, possesses high expression value CRC. Most importantly, found recruited transcription FOXA1 to bind promoter region initiated expression. Additionally, study BRD4 regulator conclusion, reveals recruits initiate expression, promoting development

Language: Английский

Citations

0
DIAPH3 in Cancer: Role and Mechanism DOI Creative Commons
Jiangling Xiong, Lanxin Hu,

Jinwei Zhu

et al.

Published: Feb. 25, 2025

Diaphanous-related formin 3 (DIAPH3) is a pivotal member of the family and serves as crucial regulator actin filament assembly. As such, DIAPH3 plays an integral role in variety cellular processes including cytokinesis, cell migration, intracellular transport. Given its fundamental importance maintaining cytoskeletal dynamics, functionally associated with numerous physiological pathological conditions, particularly cancer. In this review, we explore structural functional characteristics investigate mutational transcriptional landscape human cancers. By focusing on DIAPH3's controlling metastasis tumor microenvironment, aim to provide new insights into how contributes development progression. Altogether, believe that enhanced understanding signalosome will facilitate more precise clinical decision-making novel therapeutics against aggressive

Language: Английский

Citations

0
Analysis of extracellular vesicles of frequently used colorectal cancer cell lines DOI Creative Commons

Marie Boudná,

Nicolas Blavet, Т. В. Самойленко

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 27, 2025

Colorectal cancer (CRC) ranks as the second most prevalent malignancy globally, highlighting urgent need for more effective diagnostic and therapeutic strategies, well a deeper understanding of its molecular basis. Extensive research has demonstrated that cells actively secrete extracellular vesicles (EVs) to mediate intercellular communication at both proximal distal sites. In this study, we conducted comprehensive analysis RNA content small (sEVs) secreted into culture media five frequently utilised CRC cell lines (RKO, HCT116, HCT15, HT29, DLD1). sequencing data revealed significant insights profiles these sEVs, identifying nine protein-coding genes fourteen long non-coding (lncRNA) consistently ranked among top 30 abundant across all lines. Notably, found in sEVs were highly similar lines, indicating conserved signature. Several have been previously documented context biology, while others represent novel discoveries. These findings provide valuable cargo CRC, potentially unveiling biomarkers targets.

Language: Английский

Citations

0
Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence DOI Creative Commons
Abd Al-Rahman Mohammad Foda,

Amira Kamal El-Hawary,

Khaled Elnaghi

et al.

Tumor Biology, Journal Year: 2024, Volume and Issue: 46(1), P. 1 - 11

Published: May 7, 2024

BACKGROUND: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling activated by different extracellular signals involving “mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)”, and this induces expression of genes involved proliferation cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts potential metastasis regulator inhibiting transition to amoeboid behavior cancer types. OBJECTIVE: aim study was investigate pattern immunohistochemical MEK1 DIAPH3 adenoma (CRA) corresponding carcinoma (CRC) specimens. METHODS: examined 43 cases CRC their associated using tissue microarray technique. RESULTS: overexpressed 23 (53.5%) 20 CRA (46.5%). 11 (about 29%) which were significantly lower than (22 cases; 58%) ( P = 0.011). Both overexpression correlated 0.009) 0.002). Tumors with had higher tumor grade 0.050) perineural invasion 0.017). CONCLUSIONS: are across ACS strong correlation between them. This co- suggests possible synergistic effect DIAPH-3 ACS. Further large-scale studies required functional aspects involvement initiation metastatic process.

Language: Английский

Citations

2
DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation DOI Creative Commons
Renli Huang,

Cheng Wu,

Jialing Wen

et al.

Cancer Medicine, Journal Year: 2022, Volume and Issue: 11(23), P. 4688 - 4702

Published: May 11, 2022

Actin cytoskeleton is connected with the processes of cell proliferation and migration in colorectal cancer (CRC). However, it unknown how to accomplish these adjustments CRC by actin genes (ACGs) here we investigated role hub prognosis-related ACGs-Diaphanous-related formin 3 (DIAPH3) CRC, as a potential, novel target.The ACGs gene set from Kyoto Encyclopedia Genes Genomes (KEGG) was used group patients select univariate multivariate Cox regression for constructing prognostic model. Next, tested ACGs- DIAPH3 expression clarified shRNA constructs KM12 SW480. Activation EGFR analyzed western blot immunofluorescence.The results showed that function significant factor related clinicopathological characteristics such T stage lymph node metastasis. A model constructed four has moderate intensity 1-year Survival (AUC = 0.71). And downregulated CRC. Knockdown could promote capacity In addition, DIAPH3-silenced cells increase phosphorylation inhibiting transportation lysosome.ACGs play tumor invasion have potential predict prognosis Prognosis-related might be new biomarker inhibit progression through maintaining degradation.

Language: Английский

Citations

9
Cellular Landscape of Adrenocortical Carcinoma at Single-Nuclei Resolution DOI
David S. Tourigny, Barbara Altieri,

Ali Kerim Secener

et al.

Published: Jan. 1, 2024

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

Language: Английский

Citations

0
Nuclear TMEM199 Promotes Immune Escapes by Up-regulating PD-L1 DOI Creative Commons

Wulin You,

Hue H. Luu, Meili Li

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(12), P. 111485 - 111485

Published: Nov. 28, 2024

Language: Английский

Citations

0
Cellular landscape of adrenocortical carcinoma at single-nuclei resolution DOI Open Access
David S. Tourigny, Barbara Altieri, Kerim Secener

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 11, 2023

Abstract Adrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with molecular pathology that remain incompletely understood. To gain novel insights into cellular landscape ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC samples and analysed these alongside previously published snRNA-seq set normal glands (NAGs). We find microenvironment to be relatively devoid immune cells compared NAG tissues, consistent known high purity values for as an immunologically “cold” tumour. Our analysis identifies three separate groups are characterised by different relative compositions adrenocortical cell types, including two populations (ACC 1 2) specifically enriched in most aggressive tumours display hallmarks epithelial mesenchymal transition (EMT) dysregulated steroidogenesis, respectively. In addition types associated hypoxic metabolic signatures 3 4) prevalent among less-aggressive tumours, also identified validated population mitotically active M) strongly overexpressing genes POLQ DIAPH3 possibly supports expansion malignant lineages. The smallest specific type, 5, displays characteristics increased proliferation growth factor signalling, therefore potential progenitor-like or cell-of-origin candidate lineages involved carcinogenesis. Intriguingly, linage tracing suggests fate adopted upon differentiation appears at least partly copy number allelic balance state imprinted DLK1 / MEG3 genomic locus, which verified assessing DNA methylation status defined their type compositions. results provide new heterogeneity indicating genetic perturbations hierarchical mechanism underlying healthy renewal zonation may explain basis disease pathogenesis.

Language: Английский

Citations

0