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https://www.readbyqxmd.com/read/28548969/transcriptome-profiling-in-preadipocytes-identifies-long-noncoding-rnas-as-sam68-targets
#1
Naomi Li, Steven Hébert, Jingwen Song, Claudia L Kleinman, Stéphane Richard
The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484242/regulation-of-chk1-by-mtor-contributes-to-the-evasion-of-dna-damage-barrier-of-cancer-cells
#2
Xinhui Zhou, Weijin Liu, Xing Hu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Oncogenic transformation leads to dysregulated cell proliferation, nutrient deficiency, and hypoxia resulting in metabolic stress and increased DNA damage. In normal cells, such metabolic stress leads to inhibition of signaling through the mammalian Target of Rapamycin Complex 1 (mTORC1), reduction of protein translation, cell cycle arrest, and conservation of energy. In contrast, negative regulation of mTORC1 signaling by DNA damage is abrogated in many cancer cells, thus mTORC1 signaling remains active under microenvironmental conditions that potentially promote endogenous DNA damage...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28475806/rapamycin-reduced-pulmonary-vascular-remodelling-by-inhibiting-cell-proliferation-via-akt-mtor-signalling-pathway-down-regulation-in-the-carotid-artery-jugular-vein-shunt-pulmonary-hypertension-rat-model
#3
Xiaofan Ma, Jianping Yao, Yuan Yue, Shangming Du, Han Qin, Jian Hou, Zhongkai Wu
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease. However, effective treatments for PAH are rare. This study aimed to investigate the inhibitory effects of rapamycin on PAH in the carotid artery-jugular vein (CA-JV) shunt PAH rat model as well as the mechanism underlying these effects. METHODS: Twenty-four Sprague-Dawley rats were randomized into the following 3 groups: a control group, a CA-JV shunt group and a treatment group...
May 4, 2017: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/28461701/activation-of-a-novel-p70-s6-kinase-1-dependent-intracellular-cascade-in-the-basolateral-nucleus-of-the-amygdala-is-required-for-the-acquisition-of-extinction-memory
#4
T N Huynh, E Santini, E Mojica, A E Fink, B S Hall, R N Fetcho, L Grosenick, K Deisseroth, J E LeDoux, C Liston, E Klann
Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28428059/the-decreased-growth-performance-and-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-are-associated-with-tor-nf-%C3%AE%C2%BAb-p38mapk-nrf2-and-mlck-signaling-in-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella
#5
Yan-Lin Guo, Wei-Dan Jiang, Pei Wu, Yang Liu, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days...
April 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28410969/characterization-and-mechanism-of-phosphoinositide-3-kinases-pi3ks-members-in-insulin-induced-changes-of-protein-metabolism-in-yellow-catfish-pelteobagrus-fulvidraco
#6
Mei-Qin Zhuo, Yan-Xiong Pan, Kun Wu, Yi-Huan Xu, Zhi Luo
In the present study, seven phosphoinositide 3-kinase (PI3K) members (PI3KCa, PI3KCb, PI3KCd, PI3KCg, PI3KC2a, PI3KC2b and PI3KC3, respectively) were isolated and characterized from yellow catfish Pelteobagrus fulvidraco, and their roles in insulin-induced changes of protein metabolism were determined. These seven PI3Ks can be divided into three classes, class I (including PI3KCa, PI3KCb, PI3KCd and PI3KCg), class II (including PI3KC2a and PI3KC2b) and class III (only including PI3KC3). Compared with mammals, all of these members share similar domain structure...
April 11, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28406985/metformin-inhibited-esophageal-squamous-cell-carcinoma-proliferation-in-vitro-and-in-vivo-and-enhanced-the-anti-cancer-effect-of-cisplatin
#7
Feng Wang, Xianfei Ding, Tao Wang, Zhengzheng Shan, Jun Wang, Shaoxuan Wu, Yanyan Chi, Yana Zhang, Zhuan Lv, Liuxing Wang, Qingxia Fan
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied...
2017: PloS One
https://www.readbyqxmd.com/read/28389629/inhibition-of-p70-s6-kinase-s6k1-activity-by-a77-1726-the-active-metabolite-of-leflunomide-induces-autophagy-through-tak1-mediated-ampk-and-jnk-activation
#8
Xiulong Xu, Jing Sun, Ruilong Song, Michelle E Doscas, Ashley J Williamson, Jingsong Zhou, Jun Sun, Xinan Jiao, Xiufan Liu, Yi Li
mTOR activation suppresses autophagy by phosphorylating ULK1 at S757 and suppressing its enzymatic activity. Here we report that feedback activation of mTOR in the PI-3 kinase pathway by two p70 S6 kinase (S6K1) inhibitors (PF-4708671 and A77 1726, the active metabolite of an immunosuppressive drug leflunomide) or by S6K1 knockdown did not suppress but rather induced autophagy. Suppression of S6K1 activity led to the phosphorylation and activation of AMPK, which then phosphorylated ULK1 at S555. While mTOR feedback activation led to increased phosphorylation of ULK1 at S757, this modification did not the disrupt ULK1-AMPK interaction nor dampen ULK1 S555 phosphorylation and the induction of autophagy...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28366631/the-anti-hepatocellular-carcinoma-cell-activity-by-a-novel-mtor-kinase-inhibitor-cz415
#9
Wei Zhang, Bingyu Chen, Yu Zhang, Kaiqiang Li, Ke Hao, Luxi Jiang, Ying Wang, Xiaozhou Mou, Xiaodong Xu, Zhen Wang
Dysregulation of mammalian target of rapamycin (mTOR) in hepatocellular carcinoma (HCC) represents a valuable treatment target. Recent studies have developed a highly-selective and potent mTOR kinase inhibitor, CZ415. Here, we showed that nM concentrations of CZ415 efficiently inhibited survival and induced apoptosis in HCC cell lines (HepG2 and Huh-7) and primary-cultured human HCC cells. Meanwhile, CZ415 inhibited proliferation of HCC cells, more potently than mTORC1 inhibitors (rapamycin and RAD001). CZ415 was yet non-cytotoxic to the L02 human hepatocytes...
March 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342808/role-of-mtorc1-s6k1-signaling-pathway-in-regulation-of-hematopoietic-stem-cell-and-acute-myeloid-leukemia
#10
REVIEW
Joydeep Ghosh, Reuben Kapur
Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1)-p70 ribosomal protein kinase 1 (S6K1) signaling pathway occurs frequently in acute myeloid leukemia (AML) patients. This pathway also plays a critical role in maintaining normal cellular processes. Given the importance of leukemia stem cells (LSCs) in the development of minimal residual disease, it is critical to use therapeutic interventions that target the LSC population to prevent disease relapse. The mTORC1-S6K1 pathway has been identified as an important regulator of hematopoietic stem cell (HSC) and LSC functions...
March 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28340042/effects-of-dietary-l-arginine-levels-on-small-intestine-protein-turnover-and-the-expression-of-genes-related-to-protein-synthesis-and-proteolysis-of-layers
#11
L P Miao, C Yuan, X Y Dong, X Y Zhang, M Y Zhou, X T Zou
The aim of this study was to test the effects of dietary L-arginine (Arg) levels on protein turnover in the small intestine and the expression of genes related to protein synthesis and proteolysis of laying hens. Xinyang Black commercial laying hens (n = 864, aged 217 d) were randomly distributed to 6 treatments with 4 replicates of 36 birds. The dietary treatments were corn-corn gluten meal based diets containing 0.64, 0.86, 1.03, 1.27, 1.42 and 1.66% L-Arg, respectively. Fractional protein synthesis rate (FSR) and fractional protein gain rate (FGR) in the jejunum were the highest in the 1...
March 9, 2017: Poultry Science
https://www.readbyqxmd.com/read/28315428/p53-modulates-the-effect-of-ribosomal-protein-s6-kinase1-s6k1-on-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#12
Ling-Yi Xiao, Wai-Ming Kan
Chronic myeloid leukemia (CML) is characterized by the expression of the oncoprotein, BCR-ABL. BCR-ABL inhibitors revolutionized CML chemotherapy while blast crisis (BC) CML patients are less responsive. Since suppression of ribosomal protein S6 kinase1 (S6K1) phosphorylation reverses the resistance to BCR-ABL inhibitor in CML cells and S6K1 inhibitors augment cisplatin toxicity in lung cancer cells, we speculated that combination of S6K1 inhibitor and cisplatin may be beneficial for eliminating BC CML cells...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28314311/core-needle-biopsy-specimens-are-more-appropriate-than-surgical-specimens-for-evaluating-the-expression-of-phosphoproteins-as-biological-markers-in-invasive-breast-cancer
#13
Hyun-Ah Kim, Ji Hyun Kim, Hyang Suk Choi, Yun Gyoung Kim, Seok Joon Lee, Kang Hee Han, Min Ki Seong, Hye Sil Seol, Woo Chul Noh
BACKGROUND/AIM: To evaluate whether core needle biopsy specimens (CNBS) would be better than surgical specimens (SS) for evaluating phosphoproteins as biological markers in breast cancer. MATERIALS AND METHODS: This retrospective analysis included a total of 99 patients who had invasive breast cancer and were treated surgically between January 2012 and July 2013. The expression of phosphorylated ribosomal protein S6-kinase-1 (p-S6K1), phosphorylated protein kinase B (p-AKT), and estrogen receptor (ER) were assessed immunohistochemically on both CNBS and SS for each patient...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#14
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-1α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μm cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to antitumor drugs...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#15
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28300280/rapamycin-attenuates-baff-extended-proliferation-and-survival-via-disruption-of-mtorc1-2-signaling-in-normal-and-neoplastic-b-lymphoid-cells
#16
Qingyu Zeng, Shanshan Qin, Hai Zhang, Beibei Liu, Jiamin Qin, Xiaoxue Wang, Ruijie Zhang, Chunxiao Liu, Xiaoqing Dong, Shuangquan Zhang, Shile Huang, Long Chen
B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1, and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells...
March 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28286973/curcumin-inhibits-urothelial-tumor-development-by-suppressing-igf2-and-igf2-mediated-pi3k-akt-mtor-signaling-pathway
#17
Binqiang Tian, Yingmei Zhao, Tao Liang, Xuxiao Ye, Zuowei Li, Dongliang Yan, Qiang Fu, Yonghui Li
We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin...
March 11, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28276898/association-of-ribosomal-protein-s6-kinase-1-with-cellular-radiosensitivity-of-non-small-lung-cancer
#18
Ye Wang, Hong Mei, Qiang Shao, Jian Wang, Zhenyu Lin
PURPOSE: Ribosomal S6 kinase 1 (S6K1) plays an important role in cell proliferation, protein translation and cell survival. This study investigated the possibility of using S6K1 as a new target in the radiotherapy of non-small cell lung cancer (NSCLC) and its potential mechanism. MATERIALS AND METHODS: shRNA interference technology was applied to silence the expression of S6K1 in A549 and H460, and clonogenic assay was performed to measure the radiosensitizing effects...
March 2, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28272775/cryptotanshinone-inhibition-of-mammalian-target-of-rapamycin-pathway-is-dependent-on-oestrogen-receptor-alpha-in-breast-cancer
#19
Yanhong Pan, Junfeng Shi, Wenting Ni, Yuping Liu, Siliang Wang, Xu Wang, Zhonghong Wei, Aiyun Wang, Wenxing Chen, Yin Lu
Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF-7 breast cancer cells. However, the same results are unable to be repeated in MDA-MB-231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα-positive cancer cells, whereas ERα-negative cancer cells are insensitive to CPT...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28257457/concurrent-inhibition-of-mtorc1-and-mtorc2-by-wye-687-inhibits-renal-cell-carcinoma-cell-growth-in-vitro-and-in-vivo
#20
Xiao-Dong Pan, Dong-Hua Gu, Jia-Hui Mao, Hua Zhu, Xinfeng Chen, Bing Zheng, Yuxi Shan
Mammalian target of rapamycin (mTOR)in renal cell carcinoma (RCC) represents a valuable oncotarget for treatment. We here tested the potential anti-RCC activity by a novel mTOR kinase inhibitor WYE-687in vitro and in vivo.WYE-687 was cytotoxic and anti-proliferative to established RCC cell lines (786-O and A498) and primary human RCC cells. Yet, it was non-cytotoxic toHK-2 tubular epithelial cells.WYE-687 provoked caspase-dependent apoptosis in the RCC cells. At the molecular level, WYE-687 almost completely blocked mTORC1 (p-S6K1 and p-S6) and mTORC2 (p-Akt Ser 473) activation in both 786-Ocells and primary human RCC cells, where it downregulated both hypoxia-inducible factor (HIF)-1α and HIF-2α expression...
2017: PloS One
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