ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

Fan, Feifei; Yin, Ruxue; Wang, Liuya; Zhao, Shixin; Lv, Dan; Kangli, Yang; Geng, Shen; Yang, Ningning; Zhang, Xiao­hong; Wang, Hongmin

doi:10.7150/jca.58250

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…Our data, demonstrating higher levels of total and phospho-p53 along with lower DNA damage and apoptosis levels in the ALDH3A1/HCE-2 cells, are in agreement with this hypothesis. In accordance with our findings, Fan et al (2021) reported that ALDH3A1 was positively associated with the total p53 in tissues of lung adenocarcinoma and that a knockdown of ALDH3A1 in the lung adenocarcinoma cell line A549 resulted in lower protein levels of total p53 [ 40 ]. Similarly, Koppaka et al (2016), demonstrated that expression of ALDH3A1 in the corneal epithelium hTCEpi cell line was associated with increased cytosolic and nuclear p53 levels.…”

Section: Discussionsupporting

confidence: 92%

Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells

Voulgaridou

Theologidis

Venetikidou

et al. 2023

IJMS

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Aldehyde dehydrogenase 3A1 (ALDH3A1) oxidizes medium-chain aldehydes to their corresponding carboxylic acids. It is expressed at high rates in the human cornea, where it has been characterized as a multi-functional protein displaying various cytoprotective modes of action. Previous studies identified its association with the DNA damage response (DDR) pathway. Here, we utilized a stable transfected HCE-2 (human corneal epithelium) cell line expressing ALDH3A1, to investigate the molecular mechanisms underlying the cytoprotective role(s) of ALDH3A1. Our data revealed morphological differences among the ALDH3A1-expressing and the mock-transfected HCE-2 cells accompanied by differential expression of E-cadherin. Similarly, the ALDH3A1/HCE-2 cells demonstrated higher mobility, reduced proliferation, upregulation of ZEB1, and downregulation of CDK3, and p57. The expression of ALDH3A1 also affected cell cycle progression by inducing the sequestration of HCE-2 cells at the G2/M phase. Following 16 h cell treatments with either H2O2 or etoposide, a significantly lower percentage of ALDH3A1/HCE-2 cells were apoptotic compared to the respective treated mock/HCE-2 cells. Interestingly, the protective effect of ALDH3A1 expression under these oxidative and genotoxic conditions was accompanied by a reduced formation of γ-H2AX foci and higher levels of total and phospho (Ser15) p53. Finally, ALDH3A1 was found to be localized both in the cytoplasm and the nucleus of transfected HCE-2 cells. Its cellular compartmentalization was not affected by oxidant treatment, while the mechanism by which ALDH3A1 translocates to the nucleus remains unknown. In conclusion, ALDH3A1 protects cells from both apoptosis and DNA damage by interacting with key homeostatic mechanisms associated with cellular morphology, cell cycle, and DDR.

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Section: Discussionsupporting

confidence: 92%

Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells

Voulgaridou

Theologidis

Venetikidou

et al. 2023

IJMS

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“…Immune responses might target metabolic pathways in anticancer immunotherapy by metabolic reprogramming of immune or cancer cells [15]. ALDH3A1 had potential contribution to proliferation, cellular metabolism, and apoptosis suppression [16]. Clinical survival analysis also demonstrated that high ALDH3A1 expressions were associated with bad prognosis of lung cancer patients [17].…”

Section: Discussionmentioning

confidence: 99%

Identification of immune regulatory protein coding genes in the development of lung adenocarcinom a (LUAD)

Wen¹,

Tang²,

Wang³

et al. 2023

Trop. J. Pharm Res

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Purpose: To verify the differential expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) using RNA-seq data from eight LUAD patients Methods: TCGA database was used for extraction and analysis of RNA-seq profile in LUAD patients. Then RNA sequencing was performed using the tissue samples from eight LUAD patients for comparison. Weighted correlation network analysis (WGCNA) was applied to establish the co-expression modules and identify hub genes using RNA-seq data from the eight LUAD patients. Protein-protein interaction (PPI) analysis was used to reveal hub genes and GO analysis was performed for functional annotation including immune responses. Results: ALDH3A1, METTL7B, WFDC2 and CDH23 that had close correlation with the immune system were identified by TCGA and validated by RNA-seq from the eight LUAD patients. IL17REL was revealed as a potential oncogene in LUAD. Conclusion: This study highlighted potentially useful biomarkers associated with LUAD development and diagnosis.

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“…ALDH3A1, a member of the superfamily of NAD(P)+-dependent enzymes, can oxidize diverse aldehydes into carboxylic acids ( 72 ). ALDH3A1 shows depletion in kidney fibroblasts after TGF-β treatment ( 73 ).…”

Section: Discussionmentioning

confidence: 99%

Intimate intertwining of the pathogenesis of hypoxia and systemic sclerosis: A transcriptome integration analysis

Shi²,

Zeng³

et al. 2022

Front. Immunol.

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ObjectivesSystemic sclerosis (SSc) is an autoimmune disease caused by various pathogenic factors, including hypoxia. Hypoxia stimulates the production of the extracellular matrix to promote fibrosis. However, the integrated function and the underlying mechanism of hypoxia in SSc are unclear.MethodsIn the present study, we used Agilent SurePrint G3 Human Gene Expression v3 for the transcriptional sequencing of fibroblasts with and without hypoxia to detect differentially expressed genes (DEGs) in hypoxia. We analyzed the results with the transcriptome data of SSc lesions (GSE95065) to select the co-DEGs. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the basis of the co-DEGs using the R package ClusterProfiler, which showed that hypoxia and cross talk of hypoxia with other pathogenic factors are involved in the pathogenesis of SSc. Furthermore, we constructed a protein–protein interaction (PPI) network of co-DEGs and screened two significant functional expression modules.ResultsWe identified nine hub genes (ALDH1A1, EGF, NOX4, LYN, DNTT, PTGS2, TKT, ACAA2, and ALDH3A1). These genes affect the pentose phosphate pathway, oxidative stress, and lipolysis.ConclusionOur study provides insights into the mechanisms underlying the effects of hypoxia on SSc pathogenesis, which will help to better understand SSc pathogenesis and develop new therapeutic strategies for SSc.

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ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma

Cited by 8 publications

References 40 publications

Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells

Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells

Identification of immune regulatory protein coding genes in the development of lung adenocarcinom a (LUAD)

Intimate intertwining of the pathogenesis of hypoxia and systemic sclerosis: A transcriptome integration analysis

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