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https://www.readbyqxmd.com/read/29667179/characteristics-of-genomic-alterations-of-lung-adenocarcinoma-in-young-never-smokers
#1
Wenxin Luo, Panwen Tian, Yue Wang, Heng Xu, Lu Chen, Chao Tang, Yang Shu, Shouyue Zhang, Zhoufeng Wang, Jun Zhang, Li Zhang, Lili Jiang, Lunxu Liu, Guowei Che, Chenglin Guo, Hong Zhang, Jiali Wang, Weimin Li
Non-small cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never-smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never-smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29626488/berberine-induced-modulation-of-phlpp2-akt-mst1-kinase-signaling-is-coupled-with-mitochondrial-impairment-and-hepatoma-cell-death
#2
Sugandh Saxena, Shatrunajay Shukla, Poonam Kakkar
Pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) has been known to exert tumor suppressive activity for long without much knowledge about its regulation and implications. Protein kinase B (Akt), Protein kinase C (PKC) and Ribosomal protein S6 Kinase (S6K) are known downtargets of PHLPP2, regulating a plethora of life processes viz. cell growth, survival and evasion from apoptosis. Present study decoded the crucial role of PHLPP2 in inducing apoptosis by its interaction with the newly found binding partner Mammalian sterile 20-like kinase 1 (Mst1) in berberine (BBR)-treated human hepatoma cells...
April 4, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29597279/the-hippo-pathway-immunity-and-cancer
#3
REVIEW
Zaid Taha, Helena J Janse van Rensburg, Xiaolong Yang
Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats...
March 28, 2018: Cancers
https://www.readbyqxmd.com/read/29577047/how-hippo-signaling-pathway-modulates-cardiovascular-development-and-diseases
#4
REVIEW
Wenyi Zhou, Mingyi Zhao
Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29571247/comprehensive-analysis-and-experimental-verification-of-linc01314-as-a-tumor-suppressor-in-hepatoblastoma
#5
Benji Lv, Lianhai Zhang, Runchen Miao, Xiaohong Xiang, Shunbin Dong, Ting Lin, Ke Li, Qu Kai
Hepatoblastoma (HB), as a common pediatric liver malignancy, is composed of a variety of subgroups with different clinical outcomes. Long-noncoding RNA (lncRNA) has crucial roles in cancer biology. However, the association between lncRNA and HB has not been fully investigated. In this study, we screened lncRNA expression profiles that were annotated from the GSE75271 dataset. A total of 225 differentially expressed lncRNAs (DELs) were identified based on comparison between three prognostic subgroups, and seven of them (XR_241302, XR_923061, NR_038322, XR_951687, XR_934593, NR_120317 and XR_93406) that exhibited highly predictive accuracies were selected for functional analysis...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29568120/role-of-hippo-signaling-in-regulating-immunity
#6
REVIEW
Lixin Hong, Xun Li, Dawang Zhou, Jing Geng, Lanfen Chen
The Hippo signaling pathway has been established as a key regulator of organ size control, tumor suppression, and tissue regeneration in multiple organisms. Recently, emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals. In particular, patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome. MST1/2 kinases, the mammalian orthologs of Drosophila Hippo, may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity...
March 22, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29563341/active-epithelial-hippo-signaling-in-idiopathic-pulmonary-fibrosis
#7
Jason J Gokey, Anusha Sridharan, Yan Xu, Jenna Green, Gianni Carraro, Barry R Stripp, Anne-Karina T Perl, Jeffrey A Whitsett
Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF...
March 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29562928/trees-fungi-and-bacteria-tripartite-metatranscriptomics-of-a-root-microbiome-responding-to-soil-contamination
#8
E Gonzalez, F E Pitre, A P Pagé, J Marleau, W Guidi Nissim, M St-Arnaud, M Labrecque, S Joly, E Yergeau, N J B Brereton
BACKGROUND: One method for rejuvenating land polluted with anthropogenic contaminants is through phytoremediation, the reclamation of land through the cultivation of specific crops. The capacity for phytoremediation crops, such as Salix spp., to tolerate and even flourish in contaminated soils relies on a highly complex and predominantly cryptic interacting community of microbial life. METHODS: Here, Illumina HiSeq 2500 sequencing and de novo transcriptome assembly were used to observe gene expression in washed Salix purpurea cv...
March 21, 2018: Microbiome
https://www.readbyqxmd.com/read/29550601/molecular-cloning-expression-analysis-and-localization-pattern-of-the-mst-family-in-grass-carp-ctenopharyngodon-idella
#9
Pengfei Chu, Libo He, Lv Xiong, Lifei Luo, Rong Huang, Lanjie Liao, Yongming Li, Zuoyan Zhu, Yaping Wang
The mammalian sterile 20-like (MST) family, which belongs to the serine/threonine protein kinase superfamily, has five members that can be found in mammals: STK3 (also called MST2), STK4 (MST1), STK24 (MST3), STK25 (YSK1 or SOK1), and STK26 (MST4). The MST kinases have key roles in apoptosis, immune regulation, inflammatory responses, cancer, and cell proliferation in mammals, whereas the roles and transcriptional regulatory mechanism of these kinases in teleost fish are still unclear. In this study, four STK genes (CiSTK3, CiSTK24, CiSTK25, and CiSTK26) were cloned and analyzed in grass carp (Ctenopharyngodon idella)...
March 14, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29526917/-the-critical-role-of-autophagy-in-heart-failure
#10
Yasuhiro Maejima
Autophagy is an evolutionarily conserved process for degradation of long-lived proteins and organelles that govern a number of cardiac pathologies which cause heart failure. Indeed, recent investigations have uncovered pathways that regulate autophagy in the heart and underlying mechanisms by which alterations in this process affect cardiac function and structure. One of the major roles of autophagy in cardiomyocytes is the intracellular protein quality control (PQC). Impairment of autophagy causes aggregation of damaged and/or misfolded proteins in cardiomyocytes, thereby damaging the cells which, in turn leads to pathological cardiac remodeling...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29481838/mtorc2-signaling-a-path-for-pancreatic-%C3%AE-cell-s-growth-and-function
#11
REVIEW
Ting Yuan, Blaz Lupse, Kathrin Maedler, Amin Ardestani
The mechanistic target of rapamycin (mTOR) signaling pathway is an evolutionary conserved pathway that senses signals from nutrients and growth factors to regulate cell growth, metabolism and survival. mTOR acts in two biochemically and functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which differ in terms of regulatory mechanisms, substrate specificity and functional outputs. While mTORC1 signaling has been extensively studied in islet/ β-cell biology, recent findings demonstrate a distinct role for mTORC2 in the regulation of pancreatic β-cell function and mass...
February 23, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29474739/mst1-2-kinases-modulate-glucose-uptake-for-osteoblast-differentiation-and-bone-formation
#12
Wenling Li, Yujie Deng, Bo Feng, Kingston King-Lun Mak
Bone formation and bone homeostasis are energy-expensive processes. How they are being regulated by energy needs are not completely understood. This is of high clinical importance as diabetic-induced bone loss is common where the underlying mechanisms are unclear. Here, we show that Mst1/2 are important regulators for glucose uptake during osteoblast differentiation. Genetically removal of both Mst1/2 kinases simultaneously in mice in early and mature osteoblasts respectively inhibits bone formation and bone remodeling...
February 23, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29472569/cysteine-residues-are-essential-for-dimerization-of-hippo-pathway-components-yap2l-and-taz
#13
Prem Khanal, Zongchao Jia, Xiaolong Yang
Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/threonine protein kinase, Mst1, a core component of the Hippo pathway can be activated through formation of homodimer. However, it is still unclear whether or not other components of the Hippo pathway are also regulated through dimerization...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29459865/the-role-of-mst1-in-lymphocyte-homeostasis-and-function
#14
REVIEW
Jiali Cheng, Yukai Jing, Danqing Kang, Lu Yang, Jingwen Li, Ze Yu, Zican Peng, Xingbo Li, Yin Wei, Quan Gong, Richard J Miron, Yufeng Zhang, Chaohong Liu
The Hippo pathway is an evolutionarily conserved pathway crucial for regulating tissue size and for limiting cancer development. However, recent work has also uncovered key roles for the mammalian Hippo kinases, Mst1/2, in driving appropriate immune responses by directing T cell migration, morphology, survival, differentiation, and activation. In this review, we discuss the classical signaling pathways orchestrated by the Hippo signaling pathway, and describe how Mst1/2 direct T cell function by mechanisms not seeming to involve the classical Hippo pathway...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#15
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29448246/effect-of-mst1-on-endometriosis-apoptosis-and-migration-role-of-drp1-related-mitochondrial-fission-and-parkin-required-mitophagy
#16
Qingdong Zhao, Mingxia Ye, Wen Yang, Min Wang, Mingxia Li, Chenglei Gu, Luyang Zhao, Zhe Zhang, Weidong Han, Wensheng Fan, Yuanguang Meng
BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. METHODS: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29441677/a-novel-susceptibility-locus-in-mst1-and-gene-gene-interaction-network-for-crohn-s-disease-in-the-chinese-population
#17
William K K Wu, Rui Sun, Tao Zuo, Yuanyuan Tian, Zhirong Zeng, Jeffery Ho, Justin C Y Wu, Francis K L Chan, Matthew T V Chan, Jun Yu, Joseph J Y Sung, Sunny H Wong, Maggie H Wang, Siew C Ng
The incidence of Crohn's disease is increasing in many Asian countries, but considerable differences in genetic susceptibility have been reported between Western and Asian populations. This study aimed to fine-map 23 previously reported Crohn's disease genes and identify their interactions in the Chinese population by Illumina-based targeted capture sequencing. Our results showed that the genetic polymorphism A>G at rs144982232 in MST1 showed the most significant association (P = 1.78 × 10-5; odds ratio = 4...
February 14, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29429151/the-role-of-hippo-pathway-in-cancer-stem-cell-biology
#18
REVIEW
Jae Hyung Park, Ji Eun Shin, Hyun Woo Park
The biological significance and deregulation of the Hippo pathway during organ growth and tumorigenesis have received a surge of interest in the past decade. The Hippo pathway core kinases, MST1/2 and LATS1/2, are tumor suppressors that inhibit the oncogenic nuclear function of YAP/TAZ and TEAD. In addition to earlier studies that highlight the role of Hippo pathway in organ size control, cell proliferation, and tumor development, recent evidence demonstrates its critical role in cancer stem cell biology, including EMT, drug resistance, and self-renewal...
February 28, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29406244/vitexin-protects-isoproterenol-induced-post-myocardial-injury-by-modulating-hipposignaling-and-er-stress-responses
#19
Rathinavel Ashokkumar, Sankar Jamuna, M S Sakeena Sadullah, S Niranjali Devaraj
The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29376873/lentivirus-mediated-hdac3-inhibition-attenuates-oxidative-stress-in-appswe-ps1de9-mice
#20
Linjie Yu, Yi Liu, Yuexinzi Jin, Xiang Cao, Jian Chen, Jiali Jin, Yue Gu, Xinyu Bao, Zhuoying Ren, Yun Xu, Xiaolei Zhu
Amyloid-β (Aβ) induces a burst of oxidative stress and plays a critical role in the pathogenesis of Alzheimer's disease (AD). Our previous results have shown that histone deacetylase 3 (HDAC3) inhibition ameliorates spatial memory deficits and decreases the Aβ burden in the brains of 9-month-old APPswe/PS1dE9 (APP/PS1) mice. In this study, we investigated the role of HDAC3 inhibition in oxidative stress in vivo and in vitro models of AD. HDAC3 was detected mainly in the neurons, and HDAC3 inhibition significantly decreased reactive oxygen species generation and improved primary cortical neuron viability...
2018: Journal of Alzheimer's Disease: JAD
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