A reappraisal of transcriptional regulation by NR5A1 and beta-catenin in adrenocortical carcinoma DOI Creative Commons
Enzo Lalli

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 8, 2023

Background Overexpression of the transcription factor NR5A1 and constitutive activation canonical Wnt signalling leading to nuclear translocation beta-catenin are hallmarks malignancy in adrenocortical carcinoma (ACC). Based on analysis genomic profiles H295R ACC cells, Mohan et al. ( Cancer Res . 2023; 83: 2123-2141) recently suggested that a major determinant driving proliferation differentiation malignant is interaction chromatin regulate gene expression. Methods I reanalyzed same set data generated by other published knockdown-validated target genes, Results Beta-catenin mainly found association T cell factor/lymphoid enhancer (TCF/LEF) motifs DNA. distinct sets cells. Conclusion Overall, my suggests model where overexpression principally act independently, rather than functionally interacting, drive malignancy.

Language: Английский

Proteomic analysis reveals immune-related proteins of coelomic fluid in Urechis unicinctus DOI

Sijie Wang,

Yuxin Wu,

Baiyu Li

et al.

Comparative Biochemistry and Physiology Part D Genomics and Proteomics, Journal Year: 2025, Volume and Issue: 54, P. 101427 - 101427

Published: Jan. 24, 2025

Language: Английский

Citations

0
Integrated multi-omics and experimental approaches identify fascin actin-bundling protein 1 as an unfavorable prognostic biomarker in adrenocortical carcinoma DOI Creative Commons
Ping He, Yi‐Hao Chen, Xi Ming

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
A Review on Mitotane: A Target Therapy in Adrenocortical Carcinoma DOI Open Access
Fabiano Flauto, Maria Cristina De Martino,

Chiara Vitiello

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(23), P. 4061 - 4061

Published: Dec. 4, 2024

Adrenocortical carcinomas (ACCs) are rare and aggressive malignancies of adrenal cortex, associated with largely unknown mechanisms biological development poor prognosis. Currently, mitotane is the sole approved drug for treating advanced adrenocortical being utilized more frequently as postoperative adjuvant therapy. Although it understood that targets cortex disrupts steroid production, its precise mechanism action requires further exploration. Additionally, affects cytochrome P450 enzymes, causes depolarization mitochondrial membranes, leads to an accumulation free cholesterol, ultimately resulting in cell death. Many patients treated develop disease progression over time, underlying need understand primary acquired resistance. In this manuscript, we provide overview on intracellular mitotane, exploring data regarding predictive factors response evidence resistance mechanisms. discussion, considered a real target

Language: Английский

Citations

2
Human and Murine Cell Lines for Adrenocortical Carcinoma and Pheochromocytoma DOI Creative Commons
Edlira Luca, Andrea Abate, Katharina Wang

et al.

Endocrines, Journal Year: 2024, Volume and Issue: 5(3), P. 261 - 276

Published: July 5, 2024

Adrenocortical carcinoma (ACC) and pheochromocytoma (PCC) are malignancies originating from distinct layers of the adrenal gland. ACCs arise cortex, often detected at advanced stages associated with poor prognosis. PCCs mostly benign, medulla have a variable prognosis, 10% resulting in metastasis. Genetic background strongly influences metastasis PCCs, no reliable biomarkers that predict metastatic behavior exist to date. Current therapeutic strategies for both overall limited. Thus, novel preclinical models drug screening approaches need be established aid identification more promising drugs treatment schemes. In this review, we summarize currently available human murine cell lines tumor entities.

Language: Английский

Citations

1
Fascin-1 expression is associated with neuroendocrine prostate cancer and directly suppressed by androgen receptor DOI Creative Commons
Anthony Turpin, Carine Delliaux, Pauline Parent

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(12), P. 1903 - 1914

Published: Oct. 24, 2023

Abstract Background Neuroendocrine prostate cancer (NEPC) is an aggressive form of cancer, arising from resistance to androgen-deprivation therapies. However, the molecular mechanisms associated with NEPC development and invasiveness are still poorly understood. Here we investigated expression functional significance Fascin-1 (FSCN1), a pro-metastasis actin-bundling protein poor prognosis several cancers, in neuroendocrine differentiation cancer. Methods Differential analyses using Genome Expression Omnibus (GEO) database, clinical samples cell lines were performed. Androgen or antagonist’s cellular treatments knockdown experiments used detect changes morphology, markers, migration properties vivo tumour growth. Chromatin immunoprecipitation-sequencing (ChIP-Seq) data ChIP assays analysed decipher androgen receptor (AR) binding. Results We demonstrated that FSCN1 upregulated during vitro, leading phenotypic marker expression. In human samples, restricted tumours. showed androgen-activated AR downregulates works as transcriptional repressor directly suppress antagonists alleviate this repression. addition, silencing further impairs Conclusion Collectively, our findings identify AR-repressed gene. Particularly, it involved aggressiveness. Our results provide rationale for future inhibitors patients.

Language: Английский

Citations

3
ACTH and prolactin synergistically and selectively regulate CYP17 expression and adrenal androgen production in human foetal adrenal organ cultures DOI
Grégoire Schneider, Carmen Ruggiero, Lucie Renault

et al.

European Journal of Endocrinology, Journal Year: 2023, Volume and Issue: 189(3), P. 327 - 335

Published: Aug. 25, 2023

The essential role of ACTH on the growth and function human foetal adrenal (HFA) has long been recognized. In addition, many studies have suggested a pituitary hormone prolactin (PRL) in regulation HFA, but effects this steroidogenesis gene expression are still unknown. Our objective was to investigate effect PRL steroidogenic capacities HFA.In vitro/ex vivo experimental study.We used hanging drop vitro organ culture system. First trimester HFA samples were cultured for 14 days basal conditions or treated with ACTH, PRL, combination 2 (3 11 replicates depending experiment). Steroids measured by liquid chromatography/tandem mass spectrometry immunoassay, RT-qPCR, protein immunoblot.ACTH significantly increased corticosterone, cortisol, cortisone production, both itself when together PRL. stimulation had no effect. Combined + synergistically selectively androgen (DHEAS Δ4-androstenedione) production CYP17A1 while treatment each single significant those steroids.These results important implications our understanding hormonal cues regulating during first physiological pathological warrant further characterize molecular mechanisms converging signalling regulate expression.

Language: Английский

Citations

2
N6‐methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16‐infected cervical squamous cell carcinoma DOI
Qingqing Tian,

Juqing Huang,

Qin Zhang

et al.

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2024, Volume and Issue: 51(6)

Published: April 28, 2024

Abstract Human papillomavirus (HPV) infection has been reported to be associated with N6‐methyladenosine (m6A) modification in cancers. However, the underlying mechanism by which m6A methylation participates HPV‐related cervical squamous cell carcinoma (CSCC) remains largely unclear. In this study, we observed that regulators methyltransferase like protein (METTL14) and insulin growth factor 2 mRNA binding 3 (IGF2BP3) were upregulated HPV‐positive CSCC tissues lines, their high expression predicted poor prognosis for HPV‐infected patients. Cellular functional experiments verified HPV16 oncogenes E6/E7 of METTL14 IGF2BP3 promote proliferation epithelial mesenchymal transition cells. Next, found stabilized fascin actin‐bundling 1 (FSCN1) elevated FSCN1 cells through upregulating METTL14/IGF2BP3‐mediated modification, was also validated positively worse outcomes Finally, HPV16‐positive lines SiHa CaSki transfected knockdown vector or METTL14/IGF2BP3 overexpressing FSCN1, verification performed using MTT assay, flow cytometry, wound healing assay tumour formation assay. Results indicated suppressed proliferation, migration tumorigenesis, accelerated apoptosis Their tumour‐suppressive effects abolished FSCN1. Overall, HPV advanced development modification.

Language: Английский

Citations

0
Roles and mechanisms of circular RNA in respiratory system cancers DOI Creative Commons
Nan Yang,

Meng-Wen Jiao,

Yuewen Zhang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: July 15, 2024

Circular RNAs (circRNAs) constitute a class of endogenous non-coding (ncRNAs) that lack 5'-ended cap and 3'-ended poly (A) tail form closed ring structure with covalent bonds. Due to its special structure, circRNA is resistant Exonuclease R (RNaseR), making distribution in the cytoplasm quite rich. Advanced high-throughput sequencing bioinformatics methods have revealed highly conserved, stable, disease- tissue-specific. Furthermore, increasing research has confirmed circRNA, as driver or suppressor, regulates cancer onset progression by modulating series pathophysiological mechanisms. As result, emerged clinical biomarker therapeutic intervention target. This article reviews biological functions regulatory mechanisms context respiratory progression.

Language: Английский

Citations

0
Preclinic and Translational Research in Adrenal Malignancies DOI Creative Commons
Elena Rapizzi, Andrea Abate, Mariangela Tamburello

et al.

Updates in surgery/Updates in surgery series, Journal Year: 2024, Volume and Issue: unknown, P. 167 - 176

Published: July 24, 2024

The heterogeneity of the adrenocortical carcinoma (ACC), pheochromocytoma and paraganglioma cell phenotypes requires different experimental preclinical models to reproduce peculiarity these adrenal malignancies. Different have been generated, either in vitro or vivo, as lines growing both two-dimensional three-dimensional settings; however, particular for pheochromocytoma/paraganglioma (PPGL), new are urgently needed. As vivo models, ACC cells tumor tissue xenografts subcutaneously administered immunocompromised mice localized propagation growth. For PPGL, multiple transgenic mouse now available, obtained by genetic modifications which may recapitulate human disease. Interestingly, given physiological relevance functional interaction occurring between steroidogenic-cortical chromaffin-medullary components gland, it is likely that adrenal/medulla crosstalk also affect pathogenesis progression tumors. peculiar organization mammalian adrenals with a portal system connecting cortex medulla strongly supports evolutionary importance inside same gland.

Language: Английский

Citations

0
A reappraisal of transcriptional regulation by NR5A1 and beta-catenin in adrenocortical carcinoma DOI Creative Commons
Enzo Lalli

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 8, 2023

Background Overexpression of the transcription factor NR5A1 and constitutive activation canonical Wnt signalling leading to nuclear translocation beta-catenin are hallmarks malignancy in adrenocortical carcinoma (ACC). Based on analysis genomic profiles H295R ACC cells, Mohan et al. ( Cancer Res . 2023; 83: 2123-2141) recently suggested that a major determinant driving proliferation differentiation malignant is interaction chromatin regulate gene expression. Methods I reanalyzed same set data generated by other published knockdown-validated target genes, Results Beta-catenin mainly found association T cell factor/lymphoid enhancer (TCF/LEF) motifs DNA. distinct sets cells. Conclusion Overall, my suggests model where overexpression principally act independently, rather than functionally interacting, drive malignancy.

Language: Английский

Citations

0