A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Increased fatty acid (FA) is often observed in highly proliferative tumors. FAs have been shown to modulate the secretion of proteins from tumor cells, contributing to tumor survival. However, the secreted factors affected by FA have not been systematically explored. Here, we found that treatment of oleate, a monounsaturated omega-9 FA, promoted the proliferation of HepG2 cells. To examine the secreted factors associated with oleate-induced cell proliferation, we performed a comprehensive secretome profiling of oleate-treated and untreated HepG2 cells. A comparison of the secretomes identified 349 differentially secreted proteins (DSPs; 145 upregulated and 192 downregulated) in oleate-treated samples, compared to untreated samples. The functional enrichment and network analyses of the DSPs revealed that the 145 upregulated secreted proteins by oleate treatment were mainly associated with cell proliferation-related processes, such as lipid metabolism, inflammatory response, and ER stress. Based on the network models of the DSPs, we selected six DSPs (MIF, THBS1, PDIA3, APOA1, FASN, and EEF2) that can represent such processes related to cell proliferation. Thus, our results provided a secretome profile indicative of an oleate-induced proliferation of HepG2 cell

Impacts of Visualizations on Decoy Effects

The decoy effect is a well-known, intriguing decision-making bias that is often exploited by marketing practitioners to steer consumers towards a desired purchase outcome. It demonstrates that an inclusion of an alternative in the choice set can alter one’s preference among the other choices. Although this decoy effect has been universally observed in the real world and also studied by many economists and psychologists, little is known about how to mitigate the decoy effect and help consumers make informed decisions. In this study, we conducted two experiments: a quantitative experiment with crowdsourcing and a qualitative interview study—first, the crowdsourcing experiment to see if visual interfaces can help alleviate this cognitive bias. Four types of visualizations, one-sided bar chart, two-sided bar charts, scatterplots, and parallel-coordinate plots, were evaluated with four different types of scenarios. The results demonstrated that the two types of bar charts were effective in decreasing the decoy effect. Second, we conducted a semi-structured interview to gain a deeper understanding of the decision-making strategies while making a choice. We believe that the results have an implication on showing how visualizations can have an impact on the decision-making process in our everyday life

Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data

Hyperactivated mTOR signaling in the developing brain has been implicated in multiple forms of pathology including tuberous sclerosis complex (TSC). To date, various phenotypic defects such as cortical lamination irregularity, subependymal nodule formation, dysmorphic astrocyte differentiation and dendritic malformation have been described for patients and animal models. However, downstream networks affected in the developing brain by hyperactivated mTOR signaling have yet to be characterized. Here, we present an integrated analysis of transcriptomes and proteomes generated from wild-type and Tsc1/Emx1-Cre forebrains. This led to comprehensive lists of genes and proteins whose expression levels were altered by hyperactivated mTOR signaling. Further incorporation of TSC patient data followed by functional enrichment and network analyses pointed to changes in molecular components and cellular processes associated with neuronal differentiation and morphogenesis as the key downstream events underlying developmental and morphological defects in TSC. Our results provide novel and fundamental molecular bases for understanding hyperactivated mTOR signaling-induced brain defects which can in turn facilitate identification of potential diagnostic markers and therapeutic targets for mTOR signaling-related neurological disorders. © The Author(s) 2017

Quantitative proteomic analysis of changes related to age and calorie restriction in rat liver tissue

Calorie restriction (CR) is the most frequently studied mechanism for increasing longevity, protecting against stress, and delaying age-associated diseases. Most studies have initiated CR in young animals to determine the protective effects against aging. Although aging phenomena are well-documented, the molecular mechanisms of aging and CR remain unclear. In this study, we observed changes in hepatic proteins upon age-related and dietrestricted changes in the rat liver using quantitative proteomics. Quantitative proteomes were measured using tandem mass tag (TMT) labeling followed by liquid chromatography-tandem mass spectrometry. We compared protein levels in livers from young (6-months-old) and old (25-months-old) rats with 40% calorie-restricted (YCR and OCR, respectively) or ad libitum diets. In total, 44,279 peptides and 3,134 proteins were identified and 260 differentially expressed proteins were found. Functional enrichment analysis showed that these proteins were mainly involved in glucose and fatty acid metabolism-related processes, consistent with the theory that energy metabolism regulation is dependent on age-related and calorierestricted changes in liver tissue. In addition, proteins mediating inflammation and gluconeogenesis were increased in OCR livers, but not YCR livers. These results showed that CR in old rats might not have anti-aging benefits because liver inflammation was increased. C 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis

Recent development of the chemical inhibitors specific to oncogenic KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog) mutants revives much interest to control KRAS-driven cancers. Here, we report that AIMP2-DX2, a variant of the tumor suppressor AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), acts as a cancer-specific regulator of KRAS stability, augmenting KRAS-driven tumorigenesis. AIMP2-DX2 specifically binds to the hypervariable region and G-domain of KRAS in the cytosol prior to farnesylation. Then, AIMP2-DX2 competitively blocks the access of Smurf2 (SMAD Ubiquitination Regulatory Factor 2) to KRAS, thus preventing ubiquitin-mediated degradation. Moreover, AIMP2-DX2 levels are positively correlated with KRAS levels in colon and lung cancer cell lines and tissues. We also identified a small molecule that specifically bound to the KRAS-binding region of AIMP2-DX2 and inhibited the interaction between these two factors. Treatment with this compound reduces the cellular levels of KRAS, leading to the suppression of KRAS-dependent cancer cell growth in vitro and in vivo. These results suggest the interface of AIMP2-DX2 and KRAS as a route to control KRAS-driven cancers