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Cancer Science Sep 2023Pancreatic neuroendocrine neoplasms (pNENs) are among the most frequently occurring neuroendocrine neoplasms (NENs) and require targeted therapy. High levels of fatty...
Pancreatic neuroendocrine neoplasms (pNENs) are among the most frequently occurring neuroendocrine neoplasms (NENs) and require targeted therapy. High levels of fatty acid binding protein 5 (FABP5) are involved in tumor progression, but its role in pNENs remains unclear. We investigated the mRNA and protein levels of FABP5 in pNEN tissues and cell lines and found them to be upregulated. We evaluated changes in cell proliferation using CCK-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays and examined the effects on cell migration and invasion using transwell assays. We found that knockdown of FABP5 suppressed the proliferation, migration, and invasion of pNEN cell lines, while overexpression of FABP5 had the opposite effect. Co-immunoprecipitation experiments were performed to clarify the interaction between FABP5 and fatty acid synthase (FASN). We further showed that FABP5 regulates the expression of FASN via the ubiquitin proteasome pathway and both proteins facilitate the progression of pNENs. Our study demonstrated that FABP5 acts as an oncogene by promoting lipid droplet deposition and activating the WNT/β-catenin signaling pathway. Moreover, the carcinogenic effects of FABP5 can be reversed by orlistat, providing a novel therapeutic intervention option.
Topics: Humans; Wnt Signaling Pathway; Cell Line, Tumor; Lipid Metabolism; beta Catenin; Pancreatic Neoplasms; Neuroendocrine Tumors; Fatty Acid Synthases; Cell Proliferation; Cell Movement; Gene Expression Regulation, Neoplastic; Fatty Acid-Binding Proteins; Fatty Acid Synthase, Type I
PubMed: 37302809
DOI: 10.1111/cas.15883 -
Reproductive Sciences (Thousand Oaks,... Aug 2023Atherogenic dyslipidemia-before or during pregnancy-may contribute to preeclampsia and subsequent cardiovascular disease risk. We performed a nested case-control study... (Randomized Controlled Trial)
Randomized Controlled Trial
Atherogenic dyslipidemia-before or during pregnancy-may contribute to preeclampsia and subsequent cardiovascular disease risk. We performed a nested case-control study to further understand dyslipidemia associated with preeclampsia. The cohort consisted of participants in the randomized clinical trial "Improving Reproductive Fitness Through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility" (FIT-PLESE). FIT-PLESE was designed to study the effect of a pre-fertility treatment 16-week randomized lifestyle intervention program (Nutrisystem diet + exercise + orlistat vs. training alone) on improvement in live birth rate among obese women with unexplained infertility. Of the 279 patients in FIT-PLESE, 80 delivered a viable infant. Maternal serum was analyzed across five visits: before and after lifestyle interventions and also at three pregnancy visits (16, 24, and 32 weeks gestation). Apolipoprotein lipids were measured in a blinded fashion using ion mobility. Cases were those who developed preeclampsia. Controls also had a live birth but did not develop preeclampsia. Generalized linear and mixed models with repeated measures were used to compare the mean lipoprotein lipid levels of the two groups across all visits. Complete data were available for 75 pregnancies, and preeclampsia developed in 14.5% of the pregnancies. Cholesterol/high-density lipoprotein (HDL) ratios (p < 0.003), triglycerides (p = 0.012), and triglyceride/HDL ratios, all adjusted for BMI, were worse in patients with preeclampsia (p < 0.001). Subclasses a, b, and c of highly atherogenic, very small, low-density lipoprotein (LDL) particles were higher during pregnancy for the preeclamptic women (p < 0.05). Very small LDL particle subclass d levels were significantly greater only at 24 weeks (p = 0.012). The role of highly atherogenic, very small LDL particle excess in the pathophysiology of preeclampsia awaits further investigation.
Topics: Pregnancy; Humans; Female; Pre-Eclampsia; Case-Control Studies; Atherosclerosis; Obesity; Triglycerides; Infertility; Dyslipidemias
PubMed: 36813973
DOI: 10.1007/s43032-023-01197-w