cAMP-Dependent Signaling and Ovarian Cancer

Kilanowska, Agnieszka; Ziółkowska, Agnieszka; Stasiak, Piotr; Gibas-Dorna, Magdalena

doi:10.3390/cells11233835

Cited by 14 publications

(13 citation statements)

References 171 publications

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“…IPA’s upstream analysis revealed that ADRA2A-high conditions inhibited various regulators, including TGF-β, HIF-1A, protein kinase C (PKC), and the mitogen-activated protein kinase (MAPK) pathways (Table S1). These findings align with earlier observations regarding the basal-like/squamous subtype (3) and ADRA2A (30–33). To further investigate ADRA2A’s role, we conducted additional in vitro experiments using these ADRA2A-overexpressing PDAC cells.…”

Section: Resultssupporting

confidence: 92%

“…This downregulation of MYC may be attributed to the reduction in MAPK and PKC pathway activity. However, our study is constrained by the absence of mechanistic analyses exploring the downstream pathways of ADRA2A, including the MAPK and PKC pathways (30–33). While our research demonstrated upregulation of ADRA2A resulted in reduced amino acid metabolism, reduced cellular activity, downregulation of MYC signaling, induction of the classical/progenitor subtype, and extended patient survival in PDAC, our plan is to address the limitation through comprehensive analysis in future studies.…”

Section: Discussionmentioning

confidence: 99%

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ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer

Moreno,

Ohara,

Craig

et al. 2024

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) manifests diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, with the latter known for its aggressiveness. We employed integrative transcriptome and metabolome analyses to identify potential genes contributing to the molecular subtype differentiation and its metabolic features. Transcriptome analysis in PDAC patient cohorts revealed downregulation of adrenoceptor alpha 2A (ADRA2A) in the basal-like/squamous subtype, suggesting its potential role as a candidate suppressor of this subtype. Reduced ADRA2A expression was significantly associated with a high frequency of lymph node metastasis, higher pathological grade, advanced disease stage, and decreased survival among PDAC patients.In vitroexperiments demonstrated thatADRA2Atransgene expression and ADRA2A agonist inhibited PDAC cell invasion. Additionally, ADRA2A-high condition downregulated the basal-like/squamous gene expression signature, while upregulating the classical/progenitor gene expression signature in our PDAC patient cohort and PDAC cell lines. Metabolome analysis conducted on the PDAC cohort and cell lines revealed that elevated ADRA2A levels were associated with suppressed amino acid and carnitine/acylcarnitine metabolism, which are characteristic metabolic profiles of the classical/progenitor subtype. Collectively, our findings suggest that heightened ADRA2A expression induces transcriptome and metabolome characteristics indicative of classical/progenitor subtype with decreased disease aggressiveness in PDAC patients. These observations introduce ADRA2A as a candidate for diagnostic and therapeutic targeting in PDAC.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer

Moreno,

Ohara,

Craig

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Besides, the presence of cAMP is essential for the control and regulation of gene expression, growth, cell differentiation as well as proliferation and apoptosis ( 29 ). The versatility of cAMP-related effects depends on the expression of many factors such as adenylyl cyclase isoform, phosphodiesterase and A kinase-anchoring proteins (AKAP) ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Expression characteristics of circular RNA in human traumatic brain injury

et al. 2023

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Traumatic brain injury (TBI) causes high rates of worldwide mortality and morbidity due to the complex secondary injury cascade. Recently, circular ribonucleic acids (circRNAs) have attracted significant attention in a variety of diseases. However, their expression characteristics in human TBI are still unclear. In this study, we examined brain injury tissues from six severe TBI patients in Jinling Hospital. The TBI tissues and adjacent brain contusion tissues were used to analyze differential expression signatures of circRNAs through full-length transcriptome sequencing, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and ceRNA network construction. Our results found that there were 126 differently expressed circRNAs in TBI. Among them, 64 circRNAs were up-regulated and 62 circRNAs were down-regulated. Moreover, GO and KEGG analyses revealed that the aberrantly expressed circRNAs participated in many pathophysiological processes of TBI, especially regarding microglial cell activation, protein transport, protein processing and inflammation. Furthermore, the ceRNA (circRNA-miRNA-mRNA) network predicted that there existed strong relationship among circRNA, miRNA and mRNA. Taken together, our results indicated for the first time that the expression profiles of circRNAs were different after human TBI. In addition, we found the signaling pathways that were related to circRNAs and predicted a ceRNA network, which provided new insight of circRNAs in human TBI.

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“…Previous studies had revealed that protein kinase A (PKA) is involved in cancer transformation [ 27 ]. The occurrence and development of LIHC, OV, GBM, and ESCC are closely related to PKA [ 28 – 31 ], which reflects the potential association between ACBD3 and various tumors.…”

Section: Discussionmentioning

confidence: 99%

Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study

Ma,

Huang,

Shi

et al. 2023

Eur J Med Res

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Background Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. Methods Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. Results When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. Conclusion According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.

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cAMP-Dependent Signaling and Ovarian Cancer

Cited by 14 publications

References 171 publications

ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer

ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer

Expression characteristics of circular RNA in human traumatic brain injury

Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study

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