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fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

World Journal of Clinical Oncology 2024年第1期15卷 130-144页

作者： Yan Li William Lee Zhen-Gang Zhao Yi Liu Hao Cui Hao-Yu Wang Department of Gastroenterology Tianjin Third Central HospitalTianjin 300170China Biomedical Engineering Texas A&M UniversityCollege StationTX 77843United States

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality *** lipid metabolism plays crucial roles in HCC cancer cell survival,growth,and *** evidence suggests the importance of fatty acid binding proteins(FABPs)in contribution to cancer progression and metastasis;however,how these FABPs are dysregulated in cancer cells,especially in HCC,and the roles of FABPs in cancer progression have not been well *** To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer *** We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma(LIHC)as well as patient cohorts with other cancer types in this *** investigated genetic alterations of FABPs in various cancer *** expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome,enriched cancer hallmarks and oncogenes previously reported for patients with *** determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC *** We discovered that a gene cluster including five FABP family members(FABP4,FABP5,FABP8,FABP9 and FABP12)is frequently co-amplified in ***,in fact,is the most common genetic alteration for FABPs,leading to overexpression of ***5 showed the greatest differential mRNA expression comparing tumor with non-tumor *** FABP5 expression correlates well with worse patient outcomes(P<0.05).FABP5 expression highly correlates with enrichment of G2M checkpoint(r=0.33,P=1.1e-10),TP53 signaling pathway(r=0.22,P=1.7e-5)and many genes in the gene sets such as CDK1(r=0.56,P=0),CDK4(r=0.49,P=0),and TP53(r=0

关键词： Hepatocellular carcinoma fatty acid binding protein Novel target Amplification Correlated expression

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Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

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World Journal of Gastroenterology 2007年第25期13卷 3493-3499页

作者： Yoon Shin Park Yoosik Yoon Hong Seok Ahn Division of Intractable Diseases Center for Biomedical Sciences National Institute of Health 194 Tongillo Eunpyeong-gu Seoul 122-701 South Korea College of Medicine Chung Ang University 221 Heukseok-dong Dongjak-gu Seoul 156-756 South Korea Sungshin Women's University Department Food and Nutrition 5 Dongsun-Dong Sungbuk-Gu Seoul 136-742 South Korea

AIM: To investigate the effect of Platycodon grandi- florum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats. METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis. RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE signifi cantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue. CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat *** these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.

关键词： Obesity High fat diet Platycodon grandiflorum extract fatty acid binding protein Subcutaneousadipose tissue

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Specific protein-urea interactions

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Magnetic Resonance Letters 2022年第3期2卷 131-138页

作者： Zhi Wei Wong Daiwen Yang Department of Biological Sciences National University of Singapore14 Science Drive 4Singapore117543Singapore

The mechanism of urea's action in protein denaturation remains largely *** provide an experimental basis for molecular dynamics(MD)simulations on urea-protein interactions,we investigated the effect of urea on human intestinal fatty acid binding protein(hIFABP)by nuclear magnetic resonance(NMR).Hydrogen-deuterium exchange(HDX)rates at2 M urea indicate that urea affects hIFABP in a residue-specific manner via direct urea-protein interactions and preferentially weakens hydrogen bonds between highly protected ***-specific effects of urea on NMR peak intensities and chemical shifts further support the presence of direct urea-protein ***(2D)water-rotating frame Overhauser enhancement(ROE)data shows one protein-bound water molecule in contact with Val66 and Trp82,one putative bound water molecule in interaction with Thr76 and E-F loop,and that urea at low concentrations cannot displace these protein-bound water *** urea-nuclear Overhauser effect(NOE)experiments using 15N-urea further show no tightly protein-bound urea *** results thus suggest specific,but weak or transient,urea-protein interactions,supporting the direct interaction model of urea denaturation.

关键词： protein denaturation protein-folding fatty acid binding protein Hydrogen-deuterium exchange

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