Altered RBP1 Gene Expression Impacts Epithelial Cell Retinoic Acid, Proliferation, and Microenvironment

Yu, Jianshi; Perri, Mariarita; Jones, Jace W.; Pierzchalski, Keely; Ceaicovscaia, Natalia; Cione, Erika; Kane, Maureen A.

doi:10.3390/cells11050792

Cited by 11 publications

(5 citation statements)

References 76 publications

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“…The chemokine CXCL1, vital in inflammatory diseases and tumors, shows that its increased presence in BC stroma is associated with higher tumor grade, disease recurrence, and lower patient survival 52 , 53 . RBP1, an intracellular carrier for retinol and retinaldehyde, is notably reduced in common cancers, including BC 54 . Interestingly, previous studies indicate that STC2 is involved in several malignant tumor processes and is upregulated in various cancers, leading to poorer outcomes 55 , 56 .…”

Section: Discussionmentioning

confidence: 99%

Identifying subtypes and developing prognostic models based on N6-methyladenosine and immune microenvironment related genes in breast cancer

Wang,

Li,

Mei

et al. 2024

Sci Rep

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Breast cancer (BC) is the most prevalent cancer in women globally. The tumor microenvironment (TME), comprising epithelial tumor cells and stromal elements, is vital for breast tumor development. N6-methyladenosine (m6A) modification plays a key role in RNA metabolism, influencing its various aspects such as stability and translation. There is a notable link between m6A methylation and immune cells in the TME, although this relationship is complex and not fully deciphered. In this research, BC expression and clinicopathological data from TCGA were scrutinized to assess expression profiles, mutations, and CNVs of 31 m6A genes and immune microenvironment-related genes, examining their correlations, functions, and prognostic impacts. Lasso and Cox regression identified prognostic genes for constructing a nomogram. Single-cell analyses mapped the distribution and patterns of these genes in BC cell development. We investigated associations between gene-derived risk scores and factors like immune infiltration, TME, checkpoints, TMB, CSC indices, and drug response. As a complement to computational analyses, in vitro experiments were conducted to confirm these expression patterns. We included 31 m6A regulatory genes and discovered a correlation between these genes and the extent of immune cell infiltration. Subsequently, a 7-gene risk score was generated, encompassing HSPA2, TAP1, ULBP2, CXCL1, RBP1, STC2, and FLT3. It was observed that the low-risk group exhibited better overall survival (OS) in BC, with higher immune scores but lower tumor mutational burden (TMB) and cancer stem cell (CSC) indices, as well as lower IC50 values for commonly used drugs. To enhance clinical applicability, age and stage were incorporated into the risk score, and a more comprehensive nomogram was constructed to predict OS. This nomogram was validated and demonstrated good predictive performance, with area under the curve (AUC) values for 1-year, 3-year, and 5-year OS being 0.848, 0.807, and 0.759, respectively. Our findings highlight the profound impact of prognostic-related genes on BC immune response and prognostic outcomes, suggesting that modulation of the m6A-immune pathway could offer new avenues for personalized BC treatment and potentially improve clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Identifying subtypes and developing prognostic models based on N6-methyladenosine and immune microenvironment related genes in breast cancer

Wang,

Li,

Mei

et al. 2024

Sci Rep

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“…RBP1 , an intracellular chaperone that binds retinol and retinal with high affinity, protects retinoids from non-specific oxidation and delivers retinoids to specific enzymes ( 49 ). Yu et al ( 50 ) found that altered RBP1 expression affects epithelial cell retinoic acid, proliferation, and microenvironment. However, its role in AF remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of key genes associated with atrial fibrillation in the elderly

Liu

Zeng

Wu³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and significantly increases the risk of stroke and heart failure (HF), contributing to a higher mortality rate. Increasing age is a major risk factor for AF; however, the mechanisms of how aging contributes to the occurrence and progression of AF remain unclear. This study conducted weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes and determine their potential associations with aging-related AF.Materials and methodsWGCNA was performed using the AF dataset GSE2240 obtained from the Gene Expression Omnibus, which contained data from atrial myocardium in cardiac patients with permanent AF or sinus rhythm (SR). Hub genes were identified in clinical samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed.ResultsGreen and pink were the most critical modules associated with AF, from which nine hub genes, PTGDS, COLQ, ASTN2, VASH1, RCAN1, AMIGO2, RBP1, MFAP4, and ALDH1A1, were hypothesized to play key roles in the AF pathophysiology in elderly and seven of them have high diagnostic value. Functional enrichment analysis demonstrated that the green module was associated with the calcium, cyclic adenosine monophosphate (cAMP), and peroxisome proliferator-activated receptors (PPAR) signaling pathways, and the pink module may be associated with the transforming growth factor beta (TGF-β) signaling pathway in myocardial fibrosis.ConclusionWe identified nine genes that may play crucial roles in the pathophysiological mechanism of aging-related AF, among which six genes were associated with AF for the first time. This study provided novel insights into the impact of aging on the occurrence and progression of AF, and identified biomarkers and potential therapeutic targets for AF.

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“…RPB1 binds to retinol and prevents retinoids from being non‐specifically oxidized. RPB1 then transports the retinoids for further synthesis into retinoic acid (Yu et al., 2022). In PAX6 −/− mice RBP1 was found to be expressed at low levels (Holm et al., 2007).…”

Section: Discussionmentioning

confidence: 99%

Protein profiling of conjunctival impression cytology samples of aniridia subjects

Stachon,

Fecher‐Trost,

Latta

et al. 2023

Acta Ophthalmologica

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PurposeCongenital aniridia is a rare disease, which is in most cases related to PAX6 haploinsufficiency. Aniridia associated keratopathy (AAK) also belongs to ocular signs of congenital aniridia. In AAK, there is corneal epithelial thinning, corneal inflammation, vascularization and scarring. In advanced stage AAK, typically, conjunctival epithelial cells slowly replace the corneal epithelium. Based on previous results we hypothesize that alterations of the conjunctival cells in congenital aniridia may also support the corneal conjunctivalization process. The aim of this study was to identify deregulated proteins in conjunctival impression cytology samples of congenital aniridia subjects.MethodsConjunctival impression cytology samples of eight patients with congenital aniridia [age 34.5 ± 9.9 (17–51) years, 50% female] and eight healthy subjects [age 34.1 ± 11.9 (15–54) years, 50% female] were collected and analysed using mass spectrometry. Proteomic profiles were analysed in terms of molecular functions, biological processes, cellular components and pathway enrichment using the protein annotation of the evolutionary relationship (PANTHER) classification system.ResultsIn total, 3323 proteins could be verified and there were 127 deregulated proteins (p < 0.01) in congenital aniridia. From the 127 deregulated proteins (DEPs), 82 altered biological processes, 63 deregulated cellular components, 27 significantly altered molecular functions and 31 enriched signalling pathways were identified. Pathological alteration of the biological processes and molecular functions of retinol binding and retinoic acid biosynthesis, as well as lipid metabolism and apoptosis related pathways could be demonstrated.ConclusionsProtein profile of conjunctival impression cytology samples of aniridia subjects identifies alterations of retinol binding, retinoic acid biosynthesis, lipid metabolism and apoptosis related pathways. Whether these changes are directly related to PAX6 haploinsufficiency, must be investigated in further studies. These new findings offer the possibility to identify potential new drug targets.

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Altered RBP1 Gene Expression Impacts Epithelial Cell Retinoic Acid, Proliferation, and Microenvironment

Cited by 11 publications

References 76 publications

Identifying subtypes and developing prognostic models based on N6-methyladenosine and immune microenvironment related genes in breast cancer

Identifying subtypes and developing prognostic models based on N6-methyladenosine and immune microenvironment related genes in breast cancer

Identification and validation of key genes associated with atrial fibrillation in the elderly

Protein profiling of conjunctival impression cytology samples of aniridia subjects

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