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https://www.readbyqxmd.com/read/28924380/intracellular-insulin-and-impaired-autophagy-in-a-zebrafish-model-and-a-cell-model-of-type-2-diabetes
#1
Xiang-Hui Meng, Bo Chen, Jing-Pu Zhang
Type 2 diabetes mellitus is characterized by insulin resistance. However, the complete molecular mechanism remains unclear. In this study, zebrafish were fed a long-term high-fat diet to induce type 2 diabetes, which resulted in a higher body weight, body mass index, more lipid vacuoles in liver, increased insulin transcription level in liver, brain and muscle, and high fasting blood glucose in the high-fat diet zebrafish. Oppositely, the transcription levels of insulin substrate-2 and glucose transporter 2 were significantly decreased, indicating insulin signaling pathway and glucose transport impaired in the insulin-targeting tissues...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28905195/experimental-evidences-for-mir-30b-as-a-negative-regulator-of-foxo3-upregulated-by-kynurenine
#2
Zhi-Qing Duan, Yan Li, Lu Li
Molecular constituents regulated by the microenvironment components profoundly influence the propensity of cancer metastasis, a key event of estimating therapeutic actions of anticancer drugs. On one hand, kynurenine (Kyn), one of the microenvironment components, plays key roles in the metastasis of cancer cells in vivo; on the other hand, forkhead box O3 (FOXO3) can serve as a therapeutic target of various anticancer drugs. However, the effect of Kyn on FOXO3 is still not clear. The current study demonstrated that the selected dose of Kyn significantly upregulated the FOXO3 protein rather than FOXO3 messenger RNA (mRNA) in the lung cancer 95D cells...
September 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28894507/foxo-transcriptional-factors-and-long-term-living
#3
REVIEW
Ghulam Murtaza, Abida Kalsoom Khan, Rehana Rashid, Saiqa Muneer, Syed Muhammad Farid Hasan, Jianxin Chen
Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28891332/subretinal-delivery-of-erythropoietin-alleviates-the-n-methyl-n-nitrosourea-induced-photoreceptor-degeneration-and-visual-functional-impairments-an-in-vivo-and-ex-vivo-study
#4
Ye Tao, Yue Wang, Zhao Ma, Liqiang Wang, Limin Qin, Lu Wang, Yi Fei Huang, Shizhong Zhang
Retinitis pigmentosa (RP) is a heterogeneous group hereditary retinal disease that is characterized by photoreceptor degeneration. The present study sought to explore the therapeutic effects of erythropoietin (EPO) on the N-methyl-N-nitrosourea (MNU)-induced photoreceptor degeneration. The MNU-administered mouse or normal control received a subretinal injection of EPO (at the dose of 10U). Twenty-four hours after EPO injection, the retinal EPO levels of experimental animals were quantified. Subsequently, the experimental animals were subjected to optokinetic tests, ERG examination, SD-OCT examination, histology assessment, and immunohistochemistry evaluation...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28881594/the-mir-106a-363-xpcl1-mirna-cluster-induces-murine-t-cell-lymphoma-despite-transcriptional-activation-of-the-p27-kip1-cell-cycle-inhibitor
#5
Daniel A Kuppers, Thomas M Schmitt, Harry C Hwang, Lavanya Samraj, Bruce E Clurman, Matthew L Fero
The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities in vitro that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions in vivo. Mature miR-106a~363 (Mirc2) miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or Kis2), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881481/oxaliplatin-induces-muscle-loss-and-muscle-specific-molecular-changes-in-mice
#6
Claire E Feather, Justin G Lees, Preet G S Makker, David Goldstein, John B Kwok, Gila Moalem-Taylor, Patsie Polly
INTRODUCTION: Muscle wasting is a frequent, debilitating complication of cancer. The impact of colorectal cancer chemotherapeutic oxaliplatin on the development of muscle loss and associated molecular changes is of clinical importance. METHODS: C57BL/6J male mice were treated with oxaliplatin. Total body weights were measured and behavioral studies performed. Hindlimb muscle weights (gastrocnemius and soleus) were recorded in conjunction with gene and protein expression analysis...
September 7, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28869600/foxo3-mediated-chemo-protection-in-high-stage-neuroblastoma-depends-on-wild-type-tp53-and-sesn3
#7
M Rupp, J Hagenbuchner, B Rass, H Fiegl, U Kiechl-Kohlendorfer, P Obexer, M J Ausserlechner
Forkhead box O class transcription factors are homeostasis regulators that control cell death, longevity and therapy-resistance. In neuroblastoma (NB), nuclear FOXO3 correlates with stage M disease and poor prognosis. To analyze whether FOXO3 contributes to drug-resistance in this childhood cancer, we investigated how different high-stage-derived NB cells respond to the activation of an ectopic FOXO3 allele. We found endogenous FOXO3 mostly localized to the nucleus-upon activation of an ectopic, 4OHT-activated FOXO3(A3)ER fusion protein two of the cell lines underwent apoptosis, whereas in the others FOXO3-activation even increased survival during drug-treatment...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28866851/systematic-transcriptome-wide-analysis-of-mrna-mirna-interactions-reveals-the-involvement-of-mir-142-5p-and-its-target-foxo3-in-skeletal-muscle-growth-in-chickens
#8
Zhenhui Li, Bahareldin Ali Abdalla, Ming Zheng, Xiaomei He, Bolin Cai, Peigong Han, Hongjia Ouyang, Biao Chen, Qinghua Nie, Xiquan Zhang
The goal of this study was to perform a systematic transcriptome-wide analysis of mRNA-miRNA interactions and to identify candidates involved in the interplay between miRNAs and mRNAs that regulate chicken muscle growth. We used our previously published mRNA (GSE72424) and miRNA (GSE62971) deep sequencing data from two-tailed samples [i.e., the highest (h) and lowest (l) body weights] of Recessive White Rock (WRR) and Xinghua (XH) chickens to conduct integrative analyses of the miRNA-mRNA interactions involved in chicken skeletal muscle growth...
September 2, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28841705/single-nucleotide-polymorphisms-at-mir-146a-196a2-and-their-primary-ovarian-insufficiency-related-target-gene-regulation-in-granulosa-cells
#9
Sung Hwan Cho, Hui Jeong An, Kyung Ah Kim, Jung Jae Ko, Ji Hyang Kim, Young Ran Kim, Eun Hee Ahn, HyungChul Rah, Woo Sik Lee, Nam Keun Kim
MicroRNAs post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to identify new target genes for microRNA polymorphisms (miR-146aC>G and miR-196a2T>C) in primary ovarian insufficiency (POI). We cloned and transfected miR-146aC>G and miR-196a2T>C into human granulosa cells and used microarrays and qPCR-arrays to examine the changes in the messenger RNA expression profile. We show miR-146aC>G and miR-196a2T>C change the mRNA expression patterns in granulosa cell...
2017: PloS One
https://www.readbyqxmd.com/read/28837150/three-dimensional-tumor-cell-growth-stimulates-autophagic-flux-and-recapitulates-chemotherapy-resistance
#10
Corinna Bingel, Emily Koeneke, Johannes Ridinger, Annika Bittmann, Martin Sill, Heike Peterziel, Jagoda K Wrobel, Inga Rettig, Till Milde, Uta Fernekorn, Frank Weise, Andreas Schober, Olaf Witt, Ina Oehme
Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g., via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28782600/mir-18a-induces-myotubes-atrophy-by-down-regulating-igfi
#11
Chuncheng Liu, Meng Wang, Min Chen, Kuo Zhang, Lijie Gu, Qiuyan Li, Zhengquan Yu, Ning Li, Qingyong Meng
Muscle atrophy occurs when there is a net loss of muscle mass, leading to a change in the balance between protein synthesis and protein degradation. Igf1 is important for protein synthesis in muscle cells and can induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy via the PI3K/Akt pathway in mice, consequently restoring and improving muscle mass and strength. In this study, we show that miR-18a expression is down-regulated during C2C12 myoblast differentiation and mouse tibialis anterior muscle postnatal development...
August 4, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#12
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
July 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28772207/bone-marrow-mesenchymal-stromal-cell-msc-gene-profiling-in-chronic-myeloid-leukemia-cml-patients-at-diagnosis-and-in-deep-molecular-response-induced-by-tyrosine-kinase-inhibitors-tkis
#13
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
July 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28771227/klotho-enhances-foxo3-mediated-manganese-superoxide-dismutase-expression-by-negatively-regulating-pi3k-akt-pathway-during-tacrolimus-induced-oxidative-stress
#14
Sun Woo Lim, Long Jin, Kang Luo, Jian Jin, Yoo Jin Shin, Sung Yi Hong, Chul Woo Yang
Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28769986/curcumin-induces-p53-null-hepatoma-cell-line-hep3b-apoptosis-through-the-akt-pten-foxo4-pathway
#15
An-Ting Liou, Mei-Fang Chen, Chu-Wen Yang
OBJECTIVE: Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis. RESULTS: AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations revealed that the FOXO4 protein translocated from cytosol into the nucleus after curcumin treatment...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28765909/attenuation-of-muc4-potentiates-the-anticancer-activity-of-auranofin-via-regulation-of-the-her2-akt-foxo3-pathway-in-ovarian-cancer-cells
#16
Jun Sang Bae, Jongsung Lee, Yoonkook Park, Kyungmoon Park, Jung Ryul Kim, Dong Hyu Cho, Kyu Yun Jang, See-Hyoung Park
Previously, we reported that auranofin induces apoptosis in SKOV3 cells via regulation of the IKKβ/FOXO3 pathway. In the present study, we reveal that the anticancer activity of auranofin in SKOV3 cells could be enhanced by the attenuation of MUC4 through the regulation of the Her2/Akt/FOXO3 pathway. Compared to the control-siRNA, siRNA transfection against MUC4 into SKOV3 cells accelerated the protein degradation of Her2. Under the same conditions, the expression level of phosphorylated Akt was also downregulated leading to an increase of FOXO3 in the nucleus...
July 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#17
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729699/pten-foxo3-akt-pathway-regulates-cell-death-and-mediates-morphogenetic-differentiation-of-colorectal-cancer-cells-under-simulated-microgravity
#18
Raj Pranap Arun, Divya Sivanesan, Prasanna Vidyasekar, Rama Shanker Verma
Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722347/foxo3-longevity-interactome-on-chromosome-6
#19
Timothy A Donlon, Brian J Morris, Randi Chen, Kamal H Masaki, Richard C Allsopp, D Craig Willcox, Ayako Elliott, Bradley J Willcox
FOXO3 has been implicated in longevity in multiple populations. By DNA sequencing in long-lived individuals, we identified all single nucleotide polymorphisms (SNPs) in FOXO3 and showed 41 were associated with longevity. Thirteen of these had predicted alterations in transcription factor binding sites. Those SNPs appeared to be in physical contact, via RNA polymerase II binding chromatin looping, with sites in the FOXO3 promoter, and likely function together as a cis-regulatory unit. The SNPs exhibited a high degree of LD in the Asian population, in which they define a specific longevity haplotype that is relatively common...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28713921/anti%C3%A2-lung-cancer-effect-of-glucosamine-by-suppressing-the-phosphorylation-of-foxo
#20
Zhanwu Yu, Yinghua Ju, Hongxu Liu
Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein...
September 2017: Molecular Medicine Reports
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