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https://www.readbyqxmd.com/read/28427208/identification-of-differentially-expressed-lncrnas-involved-in-transient-regeneration-of-the-neonatal-c57bl-6j-mouse-heart-by-next-generation-high-throughput-rna-sequencing
#1
Yu-Mei Chen, Hua Li, Yi Fan, Qi-Jun Zhang, Xing Li, Li-Jie Wu, Zi-Jie Chen, Chun Zhu, Ling-Mei Qian
Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427206/mir-146a-and-mir-146b-promote-proliferation-migration-and-invasion-of-follicular-thyroid-carcinoma-via-inhibition-of-st8sia4
#2
Wei Ma, Xuzi Zhao, Leilei Liang, Guangzhi Wang, Yanyan Li, Xiaolong Miao, Yongfu Zhao
Follicular thyroid carcinoma (FTC) is a more aggressive form of thyroid cancer than the common papillary type. Alpha-2,8-sialyltransferase (ST8SIA) family members are expressed in various cancers and may be associated with FTC progression. In this study, we measured ST8SIA family expression in two FTC cell lines with different invasive potentials (FTC-133 and FTC-238) and Nthy-ori 3-1 cell lines, as well as FTC and normal thyroid tissues. ST8SIA4 was downregulated in the highly invasive FTC-238 cells and FTC tissues...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427202/clinical-implications-of-genomic-profiles-in-metastatic-breast-cancer-with-a-focus-on-tp53-and-pik3ca-the-most-frequently-mutated-genes
#3
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427045/mir-142-3p-overexpression-increases-chemo-sensitivity-of-nsclc-by-inhibiting-hmgb1-mediated-autophagy
#4
Yuqing Chen, Xin Zhou, Jianou Qiao, Aihua Bao
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. METHODS: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo...
March 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28424579/grp78-at-the-centre-of-the-stage-in-cancer-and-neuroprotection
#5
REVIEW
Caty Casas
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28424413/the-snail-mir-128-axis-regulated-growth-invasion-metastasis-and-epithelial-to-mesenchymal-transition-of-gastric-cancer
#6
Wei-Wei Yu, Hong Jiang, Cun-Tai Zhang, Yang Peng
miR-128 is expressed in various tumors, but its expression and function in gastric cancer have not been defined. Thus, the goal of this study was to characterize miR-128 in gastric cancer. We found first that miR-128 is down-regulated in gastric cancer cell lines and tissues, and this dysregulation is correlated with DNA methylation and the transcription factor SNAIL. Using prediction tools, western blotting, and luciferase reporter assays, we found that Bmi-1 was the direct target of miR-128. Additionally, overexpression of miR-128 inhibited gastric cancer cell migration, invasion, and proliferation by targeting Bmi-1 in vitro and in vivo...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423703/artocarpin-an-isoprenyl-flavonoid-induces-p53-dependent-or-independent-apoptosis-via-ros-mediated-mapks-and-akt-activation-in-non-small-cell-lung-cancer-cells
#7
Ming-Horng Tsai, Ju-Fang Liu, Yao-Chang Chiang, Stephen Chu-Sung Hu, Lee-Fen Hsu, Yu-Ching Lin, Zih-Chan Lin, Hui-Chun Lee, Mei-Chuan Chen, Chieh-Liang Huang, Chiang-Wen Lee
Artocarpin has been shown to exhibit cytotoxic effects on different cancer cells, including non-small cell lung carcinoma (NSCLC, A549). However, the underlying mechanisms remain unclear. Here, we explore both p53-dependent and independent apoptosis pathways in artocarpin-treated NSCLC cells. Our results showed that artocarpin rapidly induced activation of cellular protein kinases including Erk1/2, p38 and AktS473. Inhibition of these protein kinases prevented artocarpin-induced cell death. Moreover, artocarpin-induced phosphorylation of these protein kinases and apoptosis were mediated by induction of reactive oxygen species (ROS), as pretreatment with NAC (a ROS scavenger) and Apocynin (a Nox-2 inhibitor) blocked these events...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423649/stellettin-b-induces-apoptosis-in-human-chronic-myeloid-leukemia-cells-via-targeting-pi3k-and-stat5
#8
Yali Chen, Qianxiang Zhou, Lei Zhang, Yuxu Zhong, Guanwei Fan, Zhe Zhang, Ran Wang, Meihua Jin, Yuling Qiu, Dexin Kong
Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423632/the-genetic-variants-in-the-pten-pi3k-akt-pathway-predict-susceptibility-and-ce-a-f-chemotherapy-response-to-breast-cancer-and-clinical-outcomes
#9
Xiang Li, Ruishan Zhang, Zhuangkai Liu, Shuang Li, Hong Xu
The PI3K/PTEN/AKT pathway play a critical role in balancing cell growth and death. Epidemiologic studies suggested that mutations of the PI3K/PTEN/AKT pathway genes are associated with cancer risk, yet no data are available for PTEN rs701848, PIK3CA rs2699887, and AKT1 rs2494752 polymorphism and breast cancer(BC) risk. A case-control study was performed in 920 BC patients and 908 healthy controls using the TaqMan assay method. Overall, individuals with PTEN rs701848 TC, CC and TC/CC genotypes showed significant increased BC risk (P=0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423617/the-e3-ubiquitin-ligase-nedd4-is-translationally-upregulated-and-facilitates-pancreatic-cancer
#10
Min Weng, Zhu-Lin Luo, Xiao-Ling Wu, Wei-Zheng Zeng
AIM: To determine the regulation and function of the neural precursor cell expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT signaling. METHODS: We investigated the expression of NEDD4 and the tumor suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and migration...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423596/transient-activation-of-the-pi3k-akt-pathway-promotes-newcastle-disease-virus-replication-and-enhances-anti-apoptotic-signaling-responses
#11
Yinfeng Kang, Runyu Yuan, Xiaqiong Zhao, Bin Xiang, Shimin Gao, Pei Gao, Xu Dai, Minsha Feng, Yanling Li, Peng Xie, Yulian Li, Xiaoyi Gao, Tao Ren
Viral infection activates a host's cellular phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which is involved in cell differentiation, growth, survival, and apoptosis. To elucidate molecular mechanisms in the pathogenesis of Newcastle disease virus (NDV), we demonstrated that NDV transiently activates the PI3K/Akt pathway in chicken cells at an early phase of infection. Its activation was observed as early as 15 min post-infection and gradually weakened after 24 h. Incubating cells with a PI3K inhibitor, LY294002 or wortmannin, prior to NDV infection decreased NDV progeny yields and suppressed Akt phosphorylation at early times post-infection...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423592/protective-effect-of-hydrogen-sulphide-against-myocardial-hypertrophy-in-mice
#12
Mingjing Shao, Chuanjun Zhuo, Ronghuan Jiang, Guangdong Chen, Jianmin Shan, Jing Ping, Hongjun Tian, Lina Wang, Chongguang Lin, Lirong Hu
Cardiac hypertrophy is a critical component of phenotype in the failing heart. Recently, increasing evidence has demonstrated that oxidative stress plays an important role in the pathogenesis of myocardial hypertrophy. In the present study, we generated a mouse model of transverse aortic constriction (TAC) to investigate whether hydrogen sulfide (H2S) has protective effects against cardiac hypertrophy. Left ventricular structure was analyzed by two-dimensional echocardiography. Oxidative stress was evaluated by measuring malondialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen specie in the myocardium...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423589/role-of-microrna-21-in-radiosensitivity-in-non-small-cell-lung-cancer-cells-by-targeting-pdcd4-gene
#13
Li-Peng Jiang, Chun-Yan He, Zhi-Tu Zhu
This study aims to explore the effects of microRNA-21 (miR-21) on radiosensitivity in non-small cell lung cancer (NSCLC) by targeting programmed cell deanth 4 (PDCD4) and regulating PI3K/AKT/mTOR signaling pathway. Cancer tissues and adjacent normal tissues were collected from 97 NSCLC patients who received a standard radiotherapy regimen. TUNEL assay was applied to determine cell apoptosis in tissues. The qRT-PCR assay was used to detect the expressions of miR-21 expression and PDCD4 mRNA. The protein expressions of PDCD4 and PI3K/AKT/mTOR signaling pathway-related proteins were determined by Western blotting...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423548/axl-acts-as-a-tumor-suppressor-by-regulating-light-expression-in-t-lymphoma
#14
Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai, Hyung-Sik Kang
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423521/therapeutic-sensitivity-to-rac-gtpase-inhibition-requires-consequential-suppression-of-mtorc1-akt-and-mek-signaling-in-breast-cancer
#15
Riley A Hampsch, Kevin Shee, Darcy Bates, Lionel D Lewis, Laurent Désiré, Bertrand Leblond, Eugene Demidenko, Kurtis Stefan, Yina H Huang, Todd W Miller
Rac GTPases have oncogenic roles in cell growth, survival, and migration. We tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell lines. EHT1864-induced growth inhibition was associated with dual inhibition of the PI3K/AKT/mTORC1 and MEK/ERK pathways. Breast cancer cells harboring PIK3CA mutations or HER2 overexpression were most sensitive to Rac inhibition, suggesting that such oncogenic alterations link Rac activation with PI3K/AKT/mTORC1 and MEK/ERK signaling. Interestingly, EHT1864 decreased activation of the mTORC1 substrate p70S6K earlier than AKT inhibition, suggesting that Rac may activate mTORC1/p70S6K independently of AKT...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423362/trop2-promotes-proliferation-migration-and-metastasis-of-gallbladder-cancer-cells-by-regulating-pi3k-akt-pathway-and-inducing-emt
#16
Xinxing Li, Shifeng Teng, Yanyan Zhang, Weigang Zhang, Xianwen Zhang, Kai Xu, Houshan Yao, Jun Yao, Haolu Wang, Xiaowen Liang, Zhiqian Hu
The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423208/combined-activity-of-temozolomide-and-the-mtor-inhibitor-temsirolimus-in-metastatic-melanoma-involves-dkk1
#17
Heike Niessner, Corinna Kosnopfel, Tobias Sinnberg, Daniela Beck, Kathrin Krieg, Ines Wanke, Konstantinos Lasithiotakis, Michael Bonin, Claus Garbe, Friedegund Meier
The BRAFV600E inhibitor vemurafenib achieves remarkable clinical responses in patients with BRAF-mutant melanoma, but its effects are limited by the onset of drug resistance. In the case of resistance, chemotherapy can still be applied as second line therapy. However, it yields low response rates and strategies are urgently needed to potentiate its effects. In a previous study, we showed that the inhibition of the PI3K-AKT-mTOR pathway significantly increases sensitivity of melanoma cells to chemotherapeutic drugs (1)...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28422756/%C3%AE-catenin-and-pi3k%C3%AE-inhibition-expands-precursor-th17-cells-with-heightened-stemness-and-antitumor-activity
#18
Kinga Majchrzak, Michelle H Nelson, Jacob S Bowers, Stefanie R Bailey, Megan M Wyatt, John M Wrangle, Mark P Rubinstein, Juan C Varela, Zihai Li, Richard A Himes, Sherine S L Chan, Chrystal M Paulos
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422740/involvement-of-mir-106b-in-tumorigenic-actions-of-both-prolactin-and-estradiol
#19
Kuan-Hui Ethan Chen, Karissa Bustamante, Vi Nguyen, Ameae M Walker
Prolactin promotes a variety of cancers by an array of different mechanisms. Here, we have investigated prolactin's inhibitory effect on expression of the cell cycle-regulating protein, p21. Using a miRNA array, we identified a number of miRNAs upregulated by prolactin treatment, but one in particular that was strongly induced by prolactin and predicted to bind to the 3'UTR of p21 mRNA, miR-106b. By creating a p21 mRNA 3'UTR-luciferase mRNA construct, we demonstrated degradation of the construct in response to prolactin in human breast, prostate and ovarian cancer cell lines...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422286/isorhapontigenin-induced-cell-growth-inhibition-and-apoptosis-by-targeting-egfr-related-pathways-in-prostate-cancer
#20
Cuicui Zhu, Qingyi Zhu, Zhaomeng Wu, Yingying Yin, Dan Kang, Shan Lu, Ping Liu
Isorhapontigenin (ISO), a naturally phytopolyphenol compound existing in Chinese herb, apples and various vegetables, has attracted extensive interest in recent years for its diverse pharmacological characteristics. Increasing evidences reveal that ISO can inhibit cancer cell growth by induced apoptosis, however the molecular mechanisms is not fully understood. In this study, we found for the first time that ISO apparently induced cell growth inhibition and apoptosis by targeting EGFR and its downstream signal pathways in prostate cancer (PCa) cells both in vitro and in vivo, whereas no obviously effect on normal prostate cells...
April 19, 2017: Journal of Cellular Physiology
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