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https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#1
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339071/mir-155-5p-promotes-fibroblast-cell-proliferation-and-inhibits-foxo-signaling-pathway-in-vulvar-lichen-sclerosis-by-targeting-foxo3-and-cdkn1b
#2
Lina Ren, Yi Zhao, Xiaoxi Huo, Xin Wu
Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder. Evidence is accumulating that microRNAs (miRNAs) exert crucial roles in initiation and development of a wide range of human diseases. MiR-155-5p has been frequently reported to be implicated in the tumorigenesis and progression of multiple types of cancers, however, its biological role in VLS remains unclear. This study aimed to explore the role of miR-155-5p in VLS and clarify the potential molecular mechanisms involved. In the present study, miR-155-5p was observed to be significantly upregulated in VLS tissues...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29330285/foxo-dependent-par-4-upregulation-prevents-long-term-survival-of-residual-cells-following-pi3k-akt-inhibition
#3
Jeffrey S Damrauer, Stephanie N Phelps, Katie Amuchastegui, Ryan Lupo, Nathaniel W Mabe, Andrea Walens, Benjamin R Kroger, James V Alvarez
Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathways that regulate residual cancer cell survival may suggest opportunities for targeting these cells to prevent recurrence. Previously it was observed that the pro-apoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29328372/differential-microrna-expression-profiles-and-bioinformatics-analysis-between-young-and-aging-spontaneously-hypertensive-rats
#4
Jingfeng Wang, Jingjing Zhang, Xuefeng Ding, Yanyan Wang, Zhiming Li, Weipeng Zhao, Jianguo Jia, Jingmin Zhou, Junbo Ge
MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac hypertrophy. The present study aimed to reveal the differential expression profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs) and studied the functional annotation of predicted targets. Briefly, 3‑month‑old and 12‑month‑old SHRs (n=3/group) were subjected to echocardiography, histopathological analysis and dihydroethidium staining. Subsequently, small RNA sequencing and data processing was conducted to identify the differentially expressed miRNAs between these two groups...
January 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29326122/growth-factor-independence-1b-a-key-player-in-the-genesis-and-maintenance-of-acute-myeloid-leukaemia-and-myelodysplastic-syndrome
#5
Aniththa Thivakaran, Lacramiora Botezatu, Judith M Hönes, Judith Schütte, Lothar Vassen, Yahya S Al-Matary, Pradeep Patnana, Amos Zeller, Michael Heuser, Felicitas Thol, Razif Gabdoulline, Nadine Olberding, Daria Frank, Marina Suslo, Renata Köster, Klaus Lennartz, Andre Görgens, Bernd Giebel, Bertram Opalka, Ulrich Dührsen, Cyrus Khandanpour
Differentiation of haematopoietic stem cells is regulated by a concert of different transcription factors. Disturbed transcription factors function can be the basis of (pre)malignancies such as myelodysplastic syndrome or acute myeloid leukaemia. Growth factor independence 1b is a repressing transcription factor regulating quiescence of hematopoietic stem cellss and differentiation of erythrocytes and platelets. Here, we show that low expression of Growth factor independence 1b in blast cells is associated with an inferior prognosis of myelodysplastic syndrome and acute myeloid leukaemia patients...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29322359/expression-profiles-of-micrornas-in-oxidized-low-density-lipoprotein-stimulated-raw-264-7-cells
#6
Xiaokai Li, Siyuan Feng, Yi Luo, Keren Long, Zhenghao Lin, Jideng Ma, Anan Jiang, Long Jin, Qianzi Tang, Mingzhou Li, Xun Wang
Macrophage-derived foam cells were one of the hallmarks of atherosclerosis, and microRNAs played an important role in the formation of foam cells. In order to explore the roles of miRNA in the formation of foam cells, we investigated miRNA expression profiles in foam cells through high-throughput sequencing technology. A total of 84 miRNAs were differentially expressed between RAW 264.7 macrophages and foam cells induced by ox-LDL. Thirty miRNAs were upregulated and 54 miRNAs were downregulated. GO terms and KEGG pathways analysis revealed that the target genes of most of DE miRNAs were mainly enriched in "cell differentiation," "endocytosis," "MAPK signaling pathway," and "FoxO signaling pathway...
January 10, 2018: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/29317431/suppression-of-activated-foxo-transcription-factors-in-the-heart-prolongs-survival-in-a-mouse-model-of-laminopathies
#7
Gaelle Auguste, Priyatansh Gurha, Raffaella Lombardi, Cristian Coarfa, James T Willerson, Ali J Marian
Rationale: Mutations in the LMNA gene, encoding nuclear inner membrane protein Lamin A/C, cause distinct phenotypes, collectively referred to as laminopathies. Heart failure, conduction defects, and arrhythmias are the common causes of death in laminopathies. Objective: To identify and therapeutically target the responsible mechanism(s) for cardiac phenotype in laminopathies. Methods and Results: Whole heart RNA sequencing was performed prior to the onset of cardiac dysfunction in the Lmna-/- and matched control mice...
January 9, 2018: Circulation Research
https://www.readbyqxmd.com/read/29309929/foxo-transcription-factors-in-cancer-metabolism
#8
REVIEW
Raj Kumar Yadav, Anoop Singh Chauhan, Li Zhuang, Boyi Gan
FoxO transcription factors serve as the central regulator of cellular homeostasis and are tumor suppressors in human cancers. Recent studies have revealed that, besides their classic functions in promoting cell death and inducing cell cycle arrest, FoxOs also regulate cancer metabolism, an emerging hallmark of cancer. In this review, we summarize the regulatory mechanisms employed to control FoxO activities in the context of cancer biology, and discuss FoxO function in metabolism reprogramming in cancer and interaction with other key cancer metabolism pathways...
January 5, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29309928/foxos-in-cancer-immunity-knowns-and-unknowns
#9
REVIEW
Youcai Deng, Fangjie Wang, Tiffany Hughes, Jianhua Yu
In the tumor microenvironment (TME), cancer cells, stromal cells, and immune cells, along with their extracellular factors, have profound effects on either promoting or repressing anti-cancer immunity. Accumulating evidence has shown the paradoxical intrinsic role of the Forkhead box O (FOXO) family of transcription factors in cancer, which can act as a tumor repressor while also maintaining cancer stem cells. FOXOs also regulate cancer immunity. FOXOs promote antitumor activity through negatively regulating the expression of immunosuppressive proteins, such as programmed death 1 ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) in tumor cells or stromal cells, which can shape an immunotolerant state in the TME...
January 5, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29301793/o-glcnacylation-of-the-tumor-suppressor-foxo3-triggers-aberrant-cancer-cell-growth
#10
Heon Shin, Hyun-Jeong Cha, Keun Na, Min Jung Lee, Jin-Young Cho, Chae-Yeon Kim, Eun Kyung Kim, Chang Moo Kang, Hoguen Kim, Young-Ki Paik
Post-translational modifications of tumor suppressors can induce abnormal cell growth. Here we identify site-specific O-GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven O-GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in O-GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth. Overexpression of either O-GlcNAcylated FOXO3 (FOX-OV) or a Ser-to-Ala mutant (S284A) in PANC-1 cells indicated that S284 O-GlcNAc acts as a critical block of the FOXO tumor suppressor and induces proliferation in PANC-1 cancer cells by stimulating the MDM2-p53-p21 axis...
January 4, 2018: Cancer Research
https://www.readbyqxmd.com/read/29300322/mutations-in-emt-related-genes-in-alk-positive-crizotinib-resistant-non-small-cell-lung-cancers
#11
Jiacong Wei, Anthonie J van der Wekken, Ali Saber, Miente M Terpstra, Ed Schuuring, Wim Timens, T Jeroen N Hiltermann, Harry J M Groen, Anke van den Berg, Klaas Kok
Crizotinib is an effective drug for patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), but upon treatment, the tumors inevitably become crizotinib resistant in time. The resistance mechanisms are only partly understood. In this study, we aim to identify gene mutations associated with resistance in ALKpositive advanced non-squamous NSCLC treated with crizotinib. Four ALK positive patients with progressive disease following crizotinib treatment were identified with paired pre- and post-crizotinib tumor tissue from our previously published cohort...
January 4, 2018: Cancers
https://www.readbyqxmd.com/read/29225211/changes-in-foxo-and-proinflammatory-cytokines-in-the-late-stage-of-immobilized-fast-and-slow-muscle-atrophy
#12
Takeshi Okamoto, Shuichi Machida
The present study aimed to examine the changes in the expression of Forkhead box protein O (FOXO) and proinflammatory cytokines in both slow-twitch soleus and fast-twitch plantaris muscles following cast immobilization. Male C57BL/6 mice were subjected to cast immobilization for 7 and 21 days. Cast immobilization increased FOXO3a mRNA and total protein expression in both the soleus and plantaris muscles. Although FOXO3a phosphorylation tended to increase in response to cast immobilization in both muscles, a significant increase was evident after 21 days of immobilization only in the soleus muscle...
2017: Biomedical Research
https://www.readbyqxmd.com/read/29221208/higher-expression-of-foxos-correlates-to-better-prognosis-of-bladder-cancer
#13
Ying Zhang, Linpei Jia, Ying Zhang, Wei Ji, Hai Li
Background: We aimed to explore the expression of forkhead box class O (FOXO) and relations between expressions of FOXOs and clinicopathological characteristics and prognosis of bladder cancer. Methods: We enrolled a cohort of 276 patients with bladder cancer in our study. Expressions of FOXOs in bladder cancer tissue and adjacent tissue were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Correlations between expression of FOXOs and clinicopathological characteristics and prognosis were analyzed...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29200426/characterization-of-dfoxo-binding-sites-upstream-of-the-insulin-receptor-p2-promoter-across-the-drosophila-phylogeny
#14
Dorcas J Orengo, Montserrat Aguadé, Elvira Juan
The insulin/TOR signal transduction pathway plays a critical role in determining such important traits as body and organ size, metabolic homeostasis and life span. Although this pathway is highly conserved across the animal kingdom, the affected traits can exhibit important differences even between closely related species. Evolutionary studies of regulatory regions require the reliable identification of transcription factor binding sites. Here we have focused on the Insulin Receptor (InR) expression from its P2 promoter in the Drosophila genus, which in D...
2017: PloS One
https://www.readbyqxmd.com/read/29191656/overexpression-of-microrna-26a-protects-against-deficient-%C3%AE-cell-function-via-targeting-phosphatase-with-tensin-homology-in-mouse-models-of-type-2-diabetes
#15
Yingli Song, Di Jin, Xiaoshu Jiang, Chunmei Lv, Hui Zhu
The prevalence of type 2 diabetes mellitus (T2DM) increased rapidly in the world. The development of β-cell dysfunction is the quintessential defects in T2DM patients However, the pathogenesis of β-cell dysfunction is still unclear. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of β-cell dysfunction and T2DM. Here, we investigated the mechanisms by which miR-26a regulate β-cell function and insulin signaling pathway in high fat diet (HFD) fed and db/db T2DM mice model...
November 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29190547/low-folate-stress-reprograms-cancer-stem-cell-like-potentials-and-bioenergetics-metabolism-through-activation-of-mtor-signaling-pathway-to-promote-in-vitro-invasion-and-in-vivo-tumorigenicity-of-lung-cancers
#16
Wan-Jing Chen, Rwei-Fen S Huang
Low-folate (LF) nutritional status is associated with increased risks of lung cancer. It has unexplored effects on lung cancer malignancy, a cancer stem cell (CSC) disease. We hypothesized that LF may reprogram CSC-like potential and bioenergetics metabolism to increase metastasis potential of lung cancers. Cultivation of human non-small-cell lung cancer cells (H23) in an LF medium enhanced CSC-like properties signified by increased expressions of the CSC surface marker CD44 and pluripotency markers Sox2, Oct4 and ALDH1A1, and promoted self-renewal ability of anchorage-independent oncospheroid formation...
October 23, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29187365/foxo1-nucleo-cytoplasmic-distribution-and-unidirectional-nuclear-influx-are-the-same-in-nuclei-in-a-single-skeletal-muscle-fiber-but-vary-between-fibers
#17
Yewei Liu, Sarah J Russell, Martin F Schneider
Foxo transcription factors promote protein breakdown and atrophy of skeletal muscle fibers. Foxo transcriptional effectiveness is largely determined by phosphorylation-dependent nucleo-cytoplasmic shuttling. Imaging Foxo1-GFP over time in 124 nuclei in 68 multi-nucleated adult skeletal muscle fibers under control culture conditions reveals large variability in Foxo1-GFP nucleo-cytoplasmic concentration ratio (N/C) and in the apparent rate coefficient (kI') for Foxo1-GFP unidirectional nuclear influx (measured with efflux blocked by leptomycin B)...
November 29, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29187201/sirt1-interaction-with-active-smad2-modulates-transforming-growth-factor-%C3%AE-regulated-transcription
#18
Eva María García-Vizcaíno, Sergio Liarte, José Luis Alonso-Romero, Francisco José Nicolás
BACKGROUND: The simplicity of Transforming Growth Factor ß (TGFβ) signaling pathway, linear and non-amplified, hardly sustains its variety of responses. This is often justified by the complex regulation showed by Smad proteins, TGFβ signaling intracellular transducers, object of post-translational modifications that modulate TGFβ-dependent transcription. Protein acetylation is emerging as a compelling mechanism affecting the activities of significant transcription factors, including p53, FOXO or NF-kB...
November 29, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29182561/analysis-of-microrna-expression-in-newborns-with-differential-birth-weight-using-newborn-screening-cards
#19
Patricia Rodil-Garcia, Elvira Del Carmen Arellanes-Licea, Angélica Montoya-Contreras, Luis A Salazar-Olivo
Birth weight is an early predictor for metabolic diseases and microRNAs (miRNAs) are proposed as fetal programming participants. To evaluate the use of dried blood spots (DBS) on newborn screening cards (NSC) as a source of analyzable miRNAs, we optimized a commercial protocol to recover total miRNA from normal birth weight (NBW, n = 17-20), low birth weight (LBW, n = 17-20) and high birth weight (macrosomia, n = 17-20) newborns and analyzed the relative expression of selected miRNAs by stem-loop RT-qPCR. The possible role of miRNAs on the fetal programming of metabolic diseases was explored by bioinformatic tools...
November 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29180893/identification-of-key-genes-and-pathways-associated-with-neuropathic-pain-in-uninjured-dorsal-root-ganglion-by-using-bioinformatic-analysis
#20
Chao-Jin Chen, De-Zhao Liu, Wei-Feng Yao, Yu Gu, Fei Huang, Zi-Qing Hei, Xiang Li
Purpose: Neuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs) drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs) and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL) by using bioinformatic analysis...
2017: Journal of Pain Research
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