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      • KCI등재

        Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia

        Yeom Eunbyul,Yu Kweon 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Cancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.

      • Prominin-like regulates longevity through insulin signaling in Drosophila

        ( Tae Hoon Ryu ),( Eunbyul Yeom ),( Kyu-sun Lee ),( Kweon Yu ) 한국장기요양학회 2018 한국장기요양학회 추계학술대회자료집 Vol.2018 No.-

        CD133, also called Prominin-1, is a penta-span transmembrane protein which is known as a biomarker for human hematopoietic stem cells and mouse neuroepithelial cells. Recent studies show that CD133 is also involved in cell growth, development and tumor biology. However, the function of CD133 at the organism level is not yet investigated. Here, we found that prominin-like, a Drosophila homolog of CD133, regulates longevity and metabolism by controlling insulin signaling. prominin-like mutant flies showed extended life span and metabolic defects such as increased glucose, triglycerides levels and starvation resistance. The mRNA expression level of Drosophila insulin-like peptides (Dilps) were reduced in prominin-like mutants. Consistently, the phosphorylated AKT level, the downstream component of insulin signaling, was also decreased in prominin-like mutants. Importantly, prominin-like protein is predominantly expressed in the pars intercerebralis region with insulin producing cells of the adult brain. These results indicate that the prominin-like gene regulates longevity and glucose metabolism by controlling insulin signaling in Drosophila.

      • KCI등재

        Profiling of RNA-binding Proteins Interacting With Glucagon and Adipokinetic Hormone mRNAs

        Delaney Joe R.,Yeom Eunbyul,Chun Yoo Lim,Mun Hyejin,Howard-McGuire Marina,Millison Nathan T.,Jung Junyang,Lee Kwang-Pyo,Lee Changhan,Lee Kyu-Sun,Ko Seungbeom,Yoon Je-Hyun 한국지질동맥경화학회 2022 지질·동맥경화학회지 Vol.11 No.1

        Objective Glucagon in mammals and its homolog (adipokinetic hormone [AKH] in Drosophila melanogaster) are peptide hormones which regulate lipid metabolism by breaking down triglycerides. Although regulatory mechanisms of glucagon and AKH expression have been widely studied, post-transcriptional gene expression of glucagon has not been investigated thoroughly. In this study, we aimed to profile proteins binding with Gcg messenger RNA (mRNA) in mouse and Akh mRNA in Drosophila. Methods Drosophila Schneider 2 (S2) and mouse 3T3-L1 cell lysates were utilized for affinity pull down of Akh and Gcg mRNA respectively using biotinylated anti-sense DNA oligoes against target mRNAs. Mass spectrometry and computational network analysis revealed mRNA-interacting proteins residing in functional proximity. Results We observed that 1) 91 proteins interact with Akh mRNA from S2 cell lysates, 2) 34 proteins interact with Gcg mRNA from 3T3-L1 cell lysates. 3) Akh mRNA interactome revealed clusters of ribosomes and known RNA-binding proteins (RBPs). 4) Gcg mRNA interactome revealed mRNA-binding proteins including Plekha7, zinc finger protein, carboxylase, lipase, histone proteins and a cytochrome, Cyp2c44. 5) Levels of Gcg mRNA and its interacting proteins are elevated in skeletal muscles isolated from old mice compared to ones from young mice. Conclusion Akh mRNA in S2 cells are under active translation in a complex of RBPs and ribosomes. Gcg mRNA in mouse precursor adipocyte is in a condition distinct from Akh mRNA due to biochemical interactions with a subset of RBPs and histones. We anticipate that our study contributes to investigating regulatory mechanisms of Gcg and Akh mRNA decay, translation, and localization.

      • KCI등재SCOPUSSCIE

        Methionyl-tRNA Synthetase Regulates Lifespan in Drosophila

        Suh, Yoon Seok,Yeom, Eunbyul,Nam, Jong-Woo,Min, Kyung-Jin,Lee, Jeongsoo,Yu, Kweon Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.3

        Methionyl-tRNA synthetase (MRS) is essential for translation. MRS mutants reduce global translation, which usually increases lifespan in various genetic models. However, we found that MRS inhibited Drosophila reduced lifespan despite of the reduced protein synthesis. Microarray analysis with MRS inhibited Drosophila revealed significant changes in inflammatory and immune response genes. Especially, the expression of anti-microbial peptides (AMPs) genes was reduced. When we measured the expression levels of AMP genes during aging, those were getting increased in the control flies but reduced in MRS inhibition flies age-dependently. Interestingly, in the germ-free condition, the maximum lifespan was increased in MRS inhibition flies compared with that of the conventional condition. These findings suggest that the lifespan of MRS inhibition flies is reduced due to the down-regulated AMPs expression in Drosophila.

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