Dataset Information

Molecular mechanisms underlying the antitumoral effects of Angiotensin-(1-7) in the A549 cell line

ABSTRACT: Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system (RAS) with antitumoral effects reported in various tumoral cell lines, including the lung adenocarcinoma A549. While previous studies have shown that Ang-(1-7) modulates MAPK and PI3K-AKT signaling, the precise molecular mechanisms involved remain incompletely understood. To investigate the signaling events underlying the antitumoral effects of Ang-(1-7) in lung cancer-derived cells, we employed an integrated proteomic and phosphoproteomic approach in A549 cells. We analyzed early (minutes) and late (hours) molecular responses to Ang-(1-7) treatment. The treatment resulted in time-dependent modulation of multiple signaling pathways, including significant alterations in the MAPK, PI3K-AKT, and mTOR pathways at both the protein and phosphorylation levels. Notably, widespread early dephosphorylation events were observed similar to the effects seen with other RAS peptides with antitumoral effects. Additionally, Ang-(1-7) promoted nuclear accumulation of the transcription factor FOXO1 indicating its activation. FOXO1 is known to regulate genes involved in apoptosis, cell cycle arrest, and oxidative stress, suggesting a role in mediating the peptide’s antitumoral effects. The study provides new insights into the molecular basis of Ang-(1-7)’s antitumoral activity in A549 cells and reinforce its therapeutic potential in lung cancer.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Thiago Verano-Braga

LAB HEAD: Thiago Verano-Braga

PROVIDER: PXD066687 | Pride | 2026-01-26

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MQ_parameters_Phospho-hours.txt	Txt
	MQ_parameters_Phospho-minutes.txt	Txt
	MQ_parameters_TP-hours.txt	Txt
	MQ_parameters_TP-minutes.txt	Txt
	Obvb08748_TVB.raw	Raw

Items per page:

1 - 5 of 136

Publications

Time-resolved proteomic and phosphoproteomic profiling of Angiotensin-(1-7) signaling in A549 cells.

Melo-Braga Marcella N MN Magalhães Gabriela C GC Silva Filipe A FA Kjeldsen Frank F Larsen Martin R MR Santos Robson A S RAS Verano-Braga Thiago T

Journal of proteomics 20260120

Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system (RAS) with antitumoral effects reported in various tumoral cell lines, including the human lung adenocarcinoma A549 lineage. While previous studies have shown that Ang-(1-7) modulates MAPK and PI3K-AKT signaling, the precise molecular mechanisms involved remain incompletely understood. To investigate the signaling events of Ang-(1-7) in lung cancer-derived cells, we employed an integrated proteomic and phosphoproteom ...[more]

PMID: 41570893

Similar Datasets

Project description:Gliomas are aggressive primary brain tumors, presenting surgery limitations due to their highly infiltrative potential. The expression of Angiotensin II (Ang II) receptors in human astrocytomas was previously associated with a poor prognosis. Accordingly, this study was undertaken to reveal the molecular mechanisms underlying Ang II actions in gliomas through the transcriptomic analysis of glioma cells exposed to Ang II. C6 glioma cells were treated with Ang II and specific antagonists of AT1 and AT2. Total RNA was isolated at three and six hours intervals and submitted to oligonucleotide microarray protocol. The differentially expressed genes were obtained by paired t-tests with p<0.05 and interpreted using Venn diagrams, functional enrichment and protein interaction network analyses. Validation of microarray results was carried out through qPCR experiments of selected genes. We found a high number of significant genes with low fold changes in gene expression at the time intervals studied. These genes were regulated in a time dependent-manner, with most gene expression changes being exclusive to one of the time intervals evaluated. Our results indicated that blocking AT1 or AT2 changed the expression of genes involved in regulation of transcription, cell cycle, cell proliferation, differentiation, apoptosis, cell adhesion, cell migration, regulation of actin cytoskeleton, protein transport and protein ubiquitination. Additionally, the signaling pathways over-represented by the significant genes were ErbB, mTOR, MAPK, neurotrophin, insulin and Wnt. Finally, interactome analyses revealed hub genes associated with cell proliferation, survival, migration, transport, structural support, neurotrophin pathway, MAPK signaling and Wnt signaling. Taken together, our findings implicate Ang II-transcriptional regulation in glioma progression by means of the modulation of genes participating in protumoral functions. This transcriptome pattern is observed upon Ang II activation of either AT1 or AT2 receptors, thereby highlighting the relevance of both receptor subtypes in glioma progression. Interactome analyses disclosed hub genes regulated by Ang II which may present higher control over their networks. These genes participate in biological functions that could enhance the degree of malignancy in gliomas and thus should be further explored. C6 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum, 100 Units/ml penicillin and 100 M-BM-5g/ml streptomycin. Cells were seeded in cell culture dishes and incubated at 37M-BM-0C/ 5% CO2 until becoming confluent. Then, these cells were pre-treated (30 minutes) with either AT1 receptor antagonist (Losartan: 10-5M) or AT2 receptor antagonist (PD123319: 10-5M) followed by Ang II treatment (10-7 M) according to the treatment scheme: Group 1 M-bM-^@M-^S control; Group 2 M-bM-^@M-^S cells only treated with Ang II; Group 3 M-bM-^@M-^S cells pre-treated (30 minutes) with Losartan and then treated with Ang II; Group 4 M-bM-^@M-^S cells pre-treated (30 minutes) with PD123319 and then treated with Ang II. To identify which genes were significantly differentially expressed, paired t-tests (p<0.05) were performed in the following comparisons: Ang II x Control (3h); Ang II x Control (6h); Ang II +Los x Ang II (3h); Ang II +Los x Ang II (6h); Ang II +PD123319 x Ang II (3h); Ang II +PD123319 x Ang II (6h).