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https://www.readbyqxmd.com/read/27924057/pazopanib-a-novel-multi-kinase-inhibitor-shows-potent-antitumor-activity-in-colon-cancer-through-puma-mediated-apoptosis
#1
Lingling Zhang, Huanan Wang, Wei Li, Juchang Zhong, Rongcheng Yu, Xinfeng Huang, Honghui Wang, Zhikai Tan, Jiangang Wang, Yingjie Zhang
Colon cancer is still the third most common cancer which has a high mortality but low five-year survival rate. Novel tyrosine kinase inhibitors (TKI) such as pazopanib become effective antineoplastic agents that show promising clinical activity in a variety of carcinoma, including colon cancer. However, the precise underlying mechanism against tumor is unclear. Here, we demonstrated that pazopanib promoted colon cancer cell apoptosis through inducing PUMA expression. Pazopanib induced p53-independent PUMA activation by inhibiting PI3K/Akt signaling pathway, thereby activating Foxo3a, which subsequently bound to the promoter of PUMA to activate its transcription...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27922594/cacna1c-in-the-prefrontal-cortex-regulates-depression-related-behaviors-via-redd1
#2
Zeeba D Kabir, Anni S Lee, Caitlin E Burgdorf, Delaney Fischer, Aditi M Rajadhyaksha, Ethan Mok, Bryant Rizzo, Richard C Rice, Kamalpreet Singh, Kristie T Ota, Danielle M Gerhard, Kathryn C Schierberl, Michael Glass, Ronald S Duman, Anjali M Rajadhyaksha
The CACNA1C gene that encodes the L-type Ca(2+) channel (LTCC) Cav1.2 subunit has emerged as a candidate risk gene for multiple neuropsychiatric disorders including bipolar disorder, major depressive disorder and schizophrenia, all marked with depression-related symptoms. Although cacna1c heterozygous (HET) mice have been previously reported to exhibit an antidepressant-like phenotype, the molecular and circuit-level dysfunction remains unknown. Here we report that viral vector-mediated deletion of cacna1c in the adult prefrontal cortex (PFC) of mice recapitulates the antidepressant-like effect observed in cacna1c HET mice using the sucrose preference test (SPT), the forced swim test (FST), and the tail suspension test (TST)...
December 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27919684/neuroprotective-effects-of-mir-27a-against-traumatic-brain-injury-via-suppressing-foxo3a-mediated-neuronal-autophagy
#3
Liqian Sun, Manman Zhao, Yan Wang, Aihua Liu, Ming Lv, Youxiang Li, Xinjian Yang, Zhongxue Wu
MicroRNA-27a (miR-27a) has been reported to be a brain-specific miRNA and aberrantly expressed in the brain suffered from traumatic brain injury (TBI). The present study is designed to investigate the potential role and molecular mechanism of miR-27a in the pathogenesis of TBI. The level of miR-27a in brain was manipulated by intracerebroventricular injection of lentiviral-encoding miR-27a before TBI induction. Real-time PCR was used to detected miR-27a and Forkhead box O3a (FoxO3a) levels in the hippocampus...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27903254/mir-96-mir-145-and-mir-9-expression-increases-and-igf-1r-and-foxo1-expression-decreases-in-peripheral-blood-mononuclear-cells-of-aging-humans
#4
Monika Budzinska, Magdalena Owczarz, Eliza Pawlik-Pachucka, Malgorzata Roszkowska-Gancarz, Przemyslaw Slusarczyk, Monika Puzianowska-Kuznicka
BACKGROUND: In mammals, the IGF-1 pathway affects the phenotype of aging. Since the function of the immune system is modulated by IGF-1, it is plausible that immunosenescence might in part result from altered control by this pathway. We therefore examined whether the expression of IGF-1R, FOXO1, and FOXO3a in peripheral blood mononuclear cells (PBMC) changes with age and if this might be due to changes in the expression of select miRNAs. METHODS: The expression of IGF-1R, FOXO1, FOXO3a, as well as of miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined in PBMC of young (27...
November 30, 2016: BMC Geriatrics
https://www.readbyqxmd.com/read/27900085/id1-upregulation-and-foxo3a-downregulation-by-epstein-barr-virus-encoded-lmp1-in-hodgkin-s-lymphoma
#5
Jun-Ichiro Ikeda, Naoki Wada, Satoshi Nojima, Shinichiro Tahara, Yoko Tsuruta, Kaori Oya, Eiichi Morii
Cancer-initiating cells (CICs) are specialized cells that have the ability to self-renew and are multipotent. We recently demonstrated that Forkhead box O3a (FoxO3a)-expressing cells exhibited a CIC-like potential in Hodgkin's lymphoma (HL). A proportion of HL patients are infected with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein (LMP) 1 downregulates FoxO3a, suggesting that FoxO3a expression may be abolished in EBV-positive HL. Inhibitors of DNA-binding (ID) proteins are highly conserved transcription factors mediating stem cell functions...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27898096/on-a-fox-hunt-functions-of-fox-transcriptional-regulators-in-bladder-cancer
#6
REVIEW
Hironobu Yamashita, Vasty Osei Amponsa, Joshua I Warrick, Zongyu Zheng, Peter E Clark, Jay D Raman, Xue-Ru Wu, Cathy Mendelsohn, David J DeGraff
Genomic and transcriptional studies have identified discrete molecular subtypes of bladder cancer. These observations could be the starting point to identify new treatments. Several members of the forkhead box (FOX) superfamily of transcription factors have been found to be differentially expressed in the different bladder cancer subtypes. In addition, the FOXA protein family are key regulators of embryonic bladder development and patterning. Both experimental and clinical data support a role for FOXA1 and FOXA2 in urothelial carcinoma...
November 29, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27881235/elucidating-the-role-of-the-foxo3a-transcription-factor-in-the-igf-1-induced-migration-and-invasion-of-uveal-melanoma-cancer-cells
#7
Fengxia Yan, Rifang Liao, Mohd Farhan, Tinghuai Wang, Jiashu Chen, Zhong Wang, Peter J Little, Wenhua Zheng
Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis...
November 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27875304/rapid-renal-regulation-of-peroxisome-proliferator-activated-receptor-gamma-coactivator-1%C3%AE-by-extracellular-regulated-kinase-1-2-in-physiological-and-pathological-conditions
#8
Justin B Collier, Ryan M Whitaker, Scott T Eblen, Rick G Schnellmann
Previous studies have shown that extracellular regulated kinase 1/2 (ERK1/2) directly inhibits mitochondrial function during cellular injury. We evaluated the role of ERK1/2 on the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) gene, a master regulator of mitochondrial function. The potent and specific MEK1/2 inhibitor trametinib rapidly blocked ERK1/2 phosphorylation, decreased cytosolic and nuclear FOXO3a/1 phosphorylation, and increased PGC-1α gene expression and its downstream mitochondrial biogenesis (MB) targets under physiological conditions in the kidney cortex and in primary renal cell cultures...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27856257/maternal-diabetes-and-high-glucose-in-vitro-trigger-sca1-cardiac-progenitor-cell-apoptosis-through-foxo3a
#9
Penghua Yang, Wendy W Yang, Xi Chen, Sunjay Kaushal, Daoyin Dong, Wei-Bin Shen
Recent controversies surrounding the authenticity of c-kit(+) cardiac progenitor cells significantly push back the advance in regenerative therapies for cardiovascular diseases. There is an urgent need for research in characterizing alternative types of cardiac progenitor cells. Towards this goal, in the present study, we determined the effect of maternal diabetes on Sca1(+) cardiac progenitor cells. Maternal diabetes induced caspase 3-dependent apoptosis in Sca1(+) cardiac progenitor cells derived from embryonic day 17...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27845405/human-endometrial-mesenchymal-stem-cells-exhibit-intrinsic-anti-tumor-properties-on-human-epithelial-ovarian-cancer-cells
#10
Shixia Bu, Qian Wang, Qiuwan Zhang, Junyan Sun, Biwei He, Charlie Xiang, Zhiwei Liu, Dongmei Lai
Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27837193/intact-initiation-of-autophagy-and-mitochondrial-fission-by-acute-exercise-in-skeletal-muscle-of-patientswith-type-2-diabetes
#11
Rikke Kruse, Andreas J T Pedersen, Jonas M Kristensen, Stine J Petersson, Jørgen F P Wojtaszewski, Kurt Højlund
AIMS: Type 2 diabetes (T2D) is characterized by insulin resistance, mitochondrial dysregulation, and, in some studies, exercise resistance in skeletal muscle. Regulation of autophagy and mitochondrial dynamics during exercise and recovery is important for skeletal muscle homeostasis, and these responses may be altered in T2D. MATERIALS AND METHODS: We examined the effect of acute exercise on markers of autophagy and mitochondrial fusion and fission in skeletal muscle biopsies from patients with T2D (n=13) and weight-matched controls (n=14) before, immediately after and 3h after an acute bout of exercise...
November 11, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27825133/foxo3a-confers-cetuximab-resistance-in-ras-wild-type-metastatic-colorectal-cancer-through-c-myc
#12
Yiyi Yu, Mengzhou Guo, Ye Wei, Shan Yu, Hong Li, Yan Wang, Xiaojing Xu, Yuehong Cui, Jiawen Tian, Li Liang, Ke Peng, Tianshu Liu
Resistance to epidermal growth factor receptor (EGFR) targeted monoclonal antibody therapy represents a clinical challenge in patients suffered from RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, the molecular mechanisms and key factors conferring this resistance are largely unknown. Forkhead transcription factors of the O class 3a (FoxO3a), an important regulator of cell survival, has been reported with dual functions in tumor recently. In this study, we found that FoxO3a was highly expressed in cetuximab resistant CRC tissues compared with cetuximab sensitive tissues...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825093/microrna-155-regulates-cell-survival-growth-and-chemosensitivity-by-targeting-foxo3a-in-breast-cancer
#13
William Kong, Lili He, Marc Coppola, Jianping Guo, Nicole N Esposito, Domenico Coppola, Jin Q Cheng
No abstract text is available yet for this article.
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27811373/mir-22-targets-ywhaz-to-inhibit-metastasis-of-hepatocellular-carcinoma-and-its-down-regulation-predicts-a-poor-survival
#14
Ming Chen, Wei Hu, Chen-Ling Xiong, Zhen Qu, Chang-Qing Yin, Yu-Hui Wang, Chang-Liang Luo, Qing Guan, Chun-Hui Yuan, Fu-Bing Wang
Many miRNAs are associated with the carcinogenesis of hepatocellular carcinoma (HCC) and some exhibit potential prognostic value. In this study, to further confirm the prognostic value of miRNAs in HCC, we employed miRNA-sequencing data of tumor tissues of 372 HCC patients released by The Cancer Genome Atlas (TCGA) and identified 3 miRNAs including miR-22, miR-9-1 and miR-9-2 could be used as independent predictors for HCC prognostic evaluation. As a tumor-suppressive miRNA, miR-22 was down-regulated in HCC tissues...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27794418/sirt3-deficiency-exacerbates-diabetic-cardiac-dysfunction-role-of-foxo3a-parkin-mediated-mitophagy
#15
REVIEW
Wenjun Yu, Beilei Gao, Na Li, Jiaxing Wang, Cuiting Qiu, Guoyong Zhang, Min Liu, Rongqing Zhang, Congye Li, Gang Ji, Yingmei Zhang
Diabetic cardiomyopathy (DCM) is often associated with suppressed cardiac autophagy, mitochondrial structural and functional impairment. Sirtuin-3 (Sirt3) has been reported to play a crucial role in mitochondrial homeostasis and confers a protective role against the onset and development of DCM although the precise mechanism(s) remains elusive. Here we hypothesized that Sirt3 exerts cardioprotection against DCM by activating Parkin-mediated mitophagy, en route to preserved mitochondrial homeostasis and suppressed cardiomyocyte apoptosis...
October 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27793938/foxo3a-is-essential-for-the-antiproliferative-and-apoptogenic-effects-of-sunitinib-in-mda-mb231-cell-line
#16
Hesham M Korashy, Osamah M Belali, Mushtaq A Ansar, Naif O Alharbi
BACKGROUND: Sunitinib (SUN), a tyrosine kinase inhibitor, is a promising treatment for triple-negative breast cancer (TNBC), the most aggressive and fast-growing type of breast cancer. Yet, the protective effect of SUN against TNBC is poorly investigated and the role of Forkhead box type O (FOXO3a) transcription factor is still unknown. MATERIALS AND METHODS: Cell proliferation was evaluated using the MTT assay. The mRNA and protein expression of apoptotic, oxidative stress and cell cycle genes were determined by real-time polymerase chain reaction (RT-PCR) and western blot analyses, respectively...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27793014/dihydromyricetin-protects-against-liver-ischemia-reperfusion-induced-apoptosis-via-activation-of-foxo3a-mediated-autophagy
#17
Yongbiao Chen, Lizhi Lv, Huifeng Pi, Weijia Qin, Jianwei Chen, Dengfang Guo, Jianyu Lin, Xiaobing Chi, Zhelong Jiang, Hejun Yang, Yi Jiang
Liver ischemia and reperfusion (I/R) injury is characterized by defective liver autophagy accompanied by alterations to the endogenous defense system. Dihydromyricetin (DHM) is a natural flavonoid that demonstrates a wide range of physiological functions, and has been implicated as a regulator of autophagy. This study investigates the protective effects of DHM pretreatment on liver injury caused by ischemia/reperfusion (I/R) and elucidates the potential mechanism of DHM-mediated protection. Mice were subjected to 60 minutes of ischemia followed by 5 hours of reperfusion...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27780851/microrna-based-therapy-of-gata2-deficient-vascular-disease
#18
Dorothee Hartmann, Jan Fiedler, Kristina Sonnenschein, Annette Just, Angelika Pfanne, Karina Zimmer, Janet Remke, Ariana Foinquinos, Malte Butzlaff, Katharina Schimmel, Lars Maegdefessel, Denise Hilfiker-Kleiner, Nico Lachmann, Andreas Schober, Natali Froese, Joerg Heineke, Johann Bauersachs, Sandor Batkai, Thomas Thum
BACKGROUND: -The transcription factor GATA2 orchestrates the expression of many endothelial-specific genes illustrating its crucial importance for endothelial cell function. The capacity of this transcription factor in orchestrating endothelial important microRNAs (miRNAs/miR) is unknown. METHODS: -Endothelial GATA2 was functionally analyzed in human endothelial cells in vitro. Endogenous siRNA-mediated knockdown and lentiviral-based overexpression were applied to decipher capacity of GATA2 in regulating cell viability and capillary formation...
October 25, 2016: Circulation
https://www.readbyqxmd.com/read/27777301/forkhead-transcription-factor-3a-foxo3a-modulates-hypoxia-signaling-via-up-regulation-of-the-von-hippel-lindau-gene-vhl
#19
Xing Liu, Xiaolian Cai, Bo Hu, Zhichao Mei, Dawei Zhang, Gang Ouyang, Jing Wang, Wei Zhang, Wuhan Xiao
FOXO3a, a member of the forkhead homeobox type O (FOXO) family of transcriptional factors, regulates cell survival in response to DNA damage, caloric restriction, and oxidative stress. The von Hippel-Lindau (VHL) tumor suppressor gene encodes a component of the E3 ubiquitin ligase complex that mediates hypoxia-inducible factor α degradation under aerobic conditions, thus acting as one of the key regulators of hypoxia signaling. However, whether FOXO3a impacts cellular hypoxia stress remains unknown. Here we show that FOXO3a directly binds to the VHL promoter and up-regulates VHL expression...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27775662/capsaicin-suppresses-cell-proliferation-induces-cell-cycle-arrest-and-ros-production-in-bladder-cancer-cells-through-foxo3a-mediated-pathways
#20
Kaiyu Qian, Gang Wang, Rui Cao, Tao Liu, Guofeng Qian, Xinyuan Guan, Zhongqiang Guo, Yu Xiao, Xinghuan Wang
Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa...
October 21, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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