Down-regulation of <i>RBP4</i> indicates a poor prognosis and correlates with immune cell infiltration in hepatocellular carcinoma

Li, Mingxing; Wang, Zhihui; Zhu, Lixu; Shui, Yifang; Zhang, Shuijun; Guo, Wenzhi

doi:10.1042/bsr20210328

Cited by 20 publications

(19 citation statements)

References 41 publications

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“…TTR was regarded as an independent prognostic factor for HCC patients, and the low serum TTR levels were associated with poor prognosis ( 49 ). RBP4 was considered a novel biomarker for predicting HCC prognosis, and decreased expression of RBP4 indicated a worse prognosis and correlated with immune infiltration in HCC ( 50 ). MB, TLR4 and ALB are involved in coronavirus biology, and are associated with COVID-19 prognosis ( 51 – 53 ).…”

Section: Discussionmentioning

confidence: 99%

Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19

et al. 2022

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Coronavirus disease 2019 (COVID‐19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.

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Section: Discussionmentioning

confidence: 99%

Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19

et al. 2022

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“…Recent data have shown an association between RBP4 and bone and joint pathology ( 81 – 84 ). RBP4 levels are significantly elevated in patients with psoriatic arthritis and psoriasis ( 80 ).…”

Section: Rbp4 In Cancer and Obesity-associated Diseasementioning

confidence: 99%

“…RBP4 is associated with the incidence of numerous types of cancer ( 84 – 89 ). RBP4 mRNA and protein expression is decreased in hepatocellular carcinoma (HCC) but high in normal tissue.…”

Section: Rbp4 In Cancer and Obesity-associated Diseasementioning

confidence: 99%

“…RBP4 mRNA and protein expression is decreased in hepatocellular carcinoma (HCC) but high in normal tissue. Higher RBP4 expression is associated with improved overall survival time in patients with HCC ( 84 ). RBP4 is associated with complement and coagulation cascades, metabolic pathways, biosynthesis of antibiotics and peroxisome proliferator-activated receptor signaling and pyruvate metabolism pathways ( 84 ).…”

Section: Rbp4 In Cancer and Obesity-associated Diseasementioning

confidence: 99%

“…Higher RBP4 expression is associated with improved overall survival time in patients with HCC ( 84 ). RBP4 is associated with complement and coagulation cascades, metabolic pathways, biosynthesis of antibiotics and peroxisome proliferator-activated receptor signaling and pyruvate metabolism pathways ( 84 ). Elevated levels of RBP4 in plasma, tumor tissue, liver and abdominal fat are associated with greater blood flow impairment and metastatic potential in patients with breast cancer ( 85 ); conversely, another study found that gene expression levels of RBP4 are significantly decreased and associated with unfavorable prognosis and pathogenesis of breast cancer ( 86 ).…”

Section: Rbp4 In Cancer and Obesity-associated Diseasementioning

confidence: 99%

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Interplay of retinol binding protein 4 with obesity and associated chronic alterations (Review)

et al. 2022

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Obesity is a multifactorial disease, defined as excessive fat deposition in adipose tissue. Adipose tissue is responsible for the production and secretion of numerous adipokines that induce metabolic disorders. Retinol-binding protein 4 (RBP4) is an adipokine that transports vitamin A or retinol in the blood. High levels of RBP4 are associated with development of metabolic disease, including obesity, insulin resistance (IR), metabolic syndrome, and type 2 diabetes (T2D). The present review summarizes the role of RBP4 in obesity and associated chronic alterations. Excessive synthesis of RBP4 contributes to inflammatory characteristic of obesity by activation of immune cells and release of proinflammatory cytokines, such as TNFα and ILs, via the Toll-like receptor/JNK pathway. The retinol-RBP4 complex inhibits insulin signaling directly in adipocytes by activating Janus kinase 2 (JAK2)/STAT5/suppressor of cytokine signaling 3 signaling. This mechanism is retinol-dependent and requires vitamin A receptor stimulation by retinoic acid 6 (STRA6). In muscle, RBP4 is associated with increased serine 307 phosphorylation of insulin receptor substrate-1, which decreases its affinity to PI3K and promotes IR. In the liver, RBP4 increases hepatic expression of phosphoenolpyruvate carboxykinase, which increases production of glucose. Elevated serum RBP4 levels are associated with β-cell dysfunction in T2D via the STRA6/JAK2/STAT1/insulin gene enhancer protein 1 pathway. By contrast, RBP4 induces endothelial inflammation via the NF-κB/nicotinamide adenine dinucleotide phosphate oxidase pathway independently of retinol and STRA6, which stimulates expression of proinflammatory molecules, such as vascular cell adhesion molecule 1, E-selectin, intercellular adhesion molecule 1, monocyte chemoattractant protein 1 and TNFα. RBP4 promotes oxidative stress by decreasing endothelial mitochondrial function; overall, it may serve as a useful biomarker in the diagnosis of obesity and prognosis of associated disease, as well as a potential therapeutic target for treatment of these diseases.

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Inhibition of STRA6 suppresses NSCLC growth via blocking STAT3/SREBP-1c axis-mediated lipogenesis

Zhou,

Wang

et al. 2024

Mol Cell Biochem

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Down-regulation of RBP4 indicates a poor prognosis and correlates with immune cell infiltration in hepatocellular carcinoma

Cited by 20 publications

References 41 publications

Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19

Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19

Interplay of retinol binding protein 4 with obesity and associated chronic alterations (Review)

Inhibition of STRA6 suppresses NSCLC growth via blocking STAT3/SREBP-1c axis-mediated lipogenesis

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