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https://www.readbyqxmd.com/read/28538438/differential-regulation-of-the-autophagy-and-proteasome-pathways-in-skeletal-muscles-in-sepsis
#1
Flavia Stana, Marija Vujovic, Dominique Mayaki, Jean-Philippe Leduc-Gaudet, Philippe Leblanc, Laurent Huck, Sabah N A Hussain
OBJECTIVES: Skeletal muscle fiber atrophy develops in response to severe sepsis, but it is unclear as to how the proteolytic pathways that are involved in its development are differentially regulated. We investigated the link between sepsis-induced fiber atrophy and activation of the proteasome and autophagy pathways and whether the degree of activation is more severe and sustained in limb muscles than it is in the diaphragm. DESIGN: Randomized controlled experiment...
May 22, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28535186/fxr-gankyrin-axis-is-involved-in-development-of-pediatric-liver-cancer
#2
Leila Valanejad, Kyle Lewis, Mary Wright, Yanjun Jiang, Amber D'Souza, Rebekah Karns, Rachel Sheridan, Anita Gupta, Kevin Bove, David Witte, James Geller, Gregory Tiao, David L Nelson, Lubov Timchenko, Nikolai Timchenko
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28534948/dual-strands-of-pre-mir%C3%A2-150-mir%C3%A2-150%C3%A2-5p-and-mir%C3%A2-150%C3%A2-3p-act-as-antitumor-mirnas-targeting-spock1-in-na%C3%A3-ve-and-castration-resistant-prostate-cancer
#3
Atsushi Okato, Takayuki Arai, Satoko Kojima, Keiichi Koshizuka, Yusaku Osako, Tetsuya Idichi, Akira Kurozumi, Yusuke Goto, Mayuko Kato, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
Analysis of our microRNA (miRNA) expression signature in human cancers has shown that guide and passenger strands of pre-miR‑150, i.e., miR‑150‑5p and miR‑150‑3p, are significantly downregulated in cancer tissues. In miRNA biogenesis, the passenger strand of miRNA is degraded and is thought to have no functions. Thus, the aim of this study was to investigate the functional significance of miR‑150‑5p and miR‑150‑3p in naïve prostate cancer (PCa) and castration-resistant prostate cancer (CRPC)...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28533900/control-of-gene-expression-through-the-nonsense-mediated-rna-decay-pathway
#4
REVIEW
Andrew Nickless, Julie M Bailis, Zhongsheng You
Nonsense-mediated RNA decay (NMD) was originally discovered as a cellular surveillance pathway that safeguards the quality of mRNA transcripts in eukaryotic cells. In its canonical function, NMD prevents translation of mutant mRNAs harboring premature termination codons (PTCs) by targeting them for degradation. However, recent studies have shown that NMD has a much broader role in gene expression by regulating the stability of many normal transcripts. In this review, we discuss the function of NMD in normal physiological processes, its dynamic regulation by developmental and environmental cues, and its association with human disease...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28530246/short-single-stranded-dna-degradation-products-augment-the-activation-of-toll-like-receptor-9
#5
Jelka Pohar, Duško Lainšček, Karolina Ivičak-Kocjan, Miša-Mojca Cajnko, Roman Jerala, Mojca Benčina
Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28528814/preclinical-study-using-malat1-small-interfering-rna-or-androgen-receptor-splicing-variant-7-degradation-enhancer-asc-j9-%C3%A2-to-suppress-enzalutamide-resistant-prostate-cancer-progression
#6
Ronghao Wang, Yin Sun, Lei Li, Yuanjie Niu, Wanying Lin, Changyi Lin, Emmanuel S Antonarakis, Jun Luo, Shuyuan Yeh, Chawnshang Chang
BACKGROUND: While androgen-deprivation-therapy with the recently developed antiandrogen enzalutamide (Enz) shows promising therapeutic benefits in men with metastatic castration-resistant prostate cancer (PCa), many patients develop resistance to Enz, which may involve the induction of the androgen receptor (AR) splicing variant 7 (AR-v7). OBJECTIVE: Our aim is to identify the mechanisms responsible for AR-v7 production and to develop novel preclinical approaches to suppress the Enz-resistant (EnzR) PCa...
May 18, 2017: European Urology
https://www.readbyqxmd.com/read/28524065/microrna-in-skin-diseases
#7
Tatiana G Ruksha, Anna V Komina, Nadezhda V Palkina
MicroRNAs are essential regulators of various cellular processes such as cell growth, differentiation, apoptosis, and the immune response, acting as factors for translational repression and/or degradation of target messenger RNA. Currently, microRNAs are considered as promising biomarkers and therapeutic targets for different pathological conditions. Skin may serve as a convenient model for microRNA modulation studies due to the comparatively easy access to targets cells. Cutaneous diseases are characterized by multiple intercellular communication pathways, triggered by diverse stimuli and mediated by heterogenous regulators, including microRNAs...
May 19, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28522867/movement-protein-of-apple-chlorotic-leaf-spot-virus-is-genetically-unstable-and-negatively-regulated-by-ribonuclease-e-in-e-coli
#8
Rahul Mohan Singh, Dharam Singh, Vipin Hallan
Movement protein (MP) of Apple chlorotic leaf spot virus (ACLSV) belongs to "30 K" superfamily of proteins and members of this family are known to show a wide array of functions. In the present study this gene was found to be genetically unstable in E. coli when transformed DH5α cells were grown at 28 °C and 37 °C. However, genetic instability was not encountered at 20 °C. Heterologous over expression failed despite the use of different transcriptional promoters and translational fusion constructs...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522832/the-fragment-hmga2-sh-3p20-from-hmga2-mrna-3-utr-promotes-the-growth-of-hepatoma-cells-by-upregulating-hmga2
#9
Yuan Wang, Fuquan Chen, Zhe Yang, Man Zhao, Shuqin Zhang, Yuen Gao, Jinyan Feng, Guang Yang, Weiying Zhang, Lihong Ye, Xiaodong Zhang
High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3'-untranslated region (3'UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3'UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521214/def1-and-dst1-play-distinct-roles-in-repair-of-ap-lesions-in-highly-transcribed-genomic-regions
#10
Norah Owiti, Christopher Lopez, Shivani Singh, Andrei Stephenson, Nayun Kim
Abasic or AP sites generated by spontaneous DNA damage accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) pathway. We have demonstrated that transcription-coupled nucleotide excision repair (NER) pathway can functionally replace BER to repair those AP sites located on the transcribed strand much like the strand specific repair of UV-induced pyrimidine dimers. Previous reports indicate that Rad26, a yeast homolog of transcription-repair coupling factor CSB, partly mediates strand-specific repair of UV-dimers as well as AP lesions...
May 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28520934/the-smap1-2-proteins-of-the-crenarchaeon-sulfolobus-solfataricus-interact-with-the-exosome-and-stimulate-a-rich-tailing-of-transcripts
#11
Birgit Märtens, Linlin Hou, Fabian Amman, Michael T Wolfinger, Elena Evguenieva-Hackenberg, Udo Bläsi
The conserved Sm and Sm-like proteins are involved in different aspects of RNA metabolism. Here, we explored the interactome of SmAP1 and SmAP2 of the crenarchaeon Sulfolobus solfataricus (Sso) to shed light on their physiological function(s). Both, SmAP1 and SmAP2 co-purified with several proteins involved in RNA-processing/modification, translation and protein turnover as well as with components of the exosome involved in 3΄ to 5΄ degradation of RNA. In follow-up studies a direct interaction with the poly(A) binding and accessory exosomal subunit DnaG was demonstrated...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28513549/brain-rna-seq-profiling-of-the-mucopolysaccharidosis-type-ii-mouse-model
#12
Marika Salvalaio, Francesca D'Avanzo, Laura Rigon, Alessandra Zanetti, Michela D'Angelo, Giorgio Valle, Maurizio Scarpa, Rosella Tomanin
Lysosomal storage disorders (LSDs) are a group of about 50 genetic metabolic disorders, mainly affecting children, sharing the inability to degrade specific endolysosomal substrates. This results in failure of cellular functions in many organs, including brain that in most patients may go through progressive neurodegeneration. In this study, we analyzed the brain of the mouse model for Hunter syndrome, a LSD mostly presenting with neurological involvement. Whole transcriptome analysis of the cerebral cortex and midbrain/diencephalon/hippocampus areas was performed through RNA-seq...
May 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28511875/visible-light-switched-cytosol-release-of-sirna-by-amphiphilic-fullerene-derivative-to-enhance-rnai-efficacy-in-vitro-and-in-vivo
#13
Jing Wang, Lifei Xie, Tao Wang, Fengxin Wu, Jie Meng, Jian Liu, Haiyan Xu
Cationic macromolecules are attractive for use as small interfering RNA (siRNA) carriers due to their performance in non-immunological reactions, customization during synthesis, and low costs compared to viral carriers. However, their low transfection efficiency substantially hinders their application in both clinical practices and academic research, which is mostly attributable to the low capacity of siRNA/cationic macromolecule complexes to escape lysosomes. To address this challenge, we designed an amphiphilic fullerene derivative (C60-Dex-NH2) for efficient and controllable siRNA delivery...
May 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28508547/functional-phosphatome-requirement-for-protein-homeostasis-networked-mitochondria-and-sarcomere-structure-in-c-%C3%A2-elegans-muscle
#14
Susann Lehmann, Joseph J Bass, Thomas F Barratt, Mohammed Z Ali, Nathaniel J Szewczyk
BACKGROUND: Skeletal muscle is central to locomotion and metabolic homeostasis. The laboratory worm Caenorhabditis elegans has been developed into a genomic model for assessing the genes and signals that regulate muscle development and protein degradation. Past work has identified a receptor tyrosine kinase signalling network that combinatorially controls autophagy, nerve signal to muscle to oppose proteasome-based degradation, and extracellular matrix-based signals that control calpain and caspase activation...
May 15, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28508407/structural-conservation-of-the-pin-domain-active-site-across-all-domains-of-life
#15
REVIEW
M Senissar, M C Manav, D E Brodersen
The PIN domain (Pil N-terminus) is a compact RNA-binding protein domain present in all domains of life. This 120-residue domain consists of a central and parallel β sheet surrounded by α helices, which together organise 4-5 acidic residues in an active site that binds one or more divalent metal ions and in many cases has endoribonuclease activity. In bacteria and archaea, the PIN domain is primarily associated with toxin-antitoxin loci, consisting of a toxin (the PIN domain nuclease) and an antitoxin that inhibits the function of the toxin under normal growth conditions...
May 15, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28507061/rnf8-mediates-histone-h3-ubiquitylation-and-promotes-glycolysis-and-tumorigenesis
#16
Yan Xia, Weiwei Yang, Ming Fa, Xinjian Li, Yugang Wang, Yuhui Jiang, Yanhua Zheng, Jong-Ho Lee, Jing Li, Zhimin Lu
Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription...
May 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28506831/cryab-promotes-the-invasion-and-metastasis-of-colorectal-cancer-via-epithelial-mesenchymal-transition
#17
Chuanbing Shi, Xiaojun Yang, Xiaodong Bu, Ning Hou, Pingsheng Chen
Alpha B-crystallin (CRYAB, HSPB5) is a protein that was first discovered in the lens of the eye. It is a member of the small heat-shock protein family (sHsps). CRYAB functions primarily as a molecular chaperone to prevent the aggregation and degradation of damaged unfolded proteins due to cellular damage resulting from heat shock, radiation, oxidative stress, and other insults, thereby promoting cell survival and preventing apoptosis. In recent years, the role of CRYAB in tumorigenesis, tumor invasion, and metastasis has received increasing attention...
May 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28506802/stealth-magnetic-nanocarriers-of-sirna-as-platform-for-breast-cancer-theranostics
#18
J Bruniaux, S Ben Djemaa, K Hervé-Aubert, H Marchais, I Chourpa, S David
The endogenous mechanism of RNA interference is more and more used in research to obtain specific down-regulation of gene expression in diseases such as breast cancer. Currently, despite the new fields of study open up by RNA interference, the rapid degradation of siRNA by nucleases and their negative charges prevent them from crossing cell membranes. To overcome these limitations, superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising alternative for nucleic acid delivery. Previously, we reported the magnetic siRNA nanovectors (MSN) formulation using electrostatic assembly of (1) SPIONs, also able to act as contrast agents for magnetic resonance imaging (MRI), (2) siRNA and (3) chitosan aiming at their protection and enhancing their transfection efficacy...
May 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28503708/stress-and-the-nonsense-mediated-rna-decay-pathway
#19
REVIEW
Alexandra E Goetz, Miles Wilkinson
Cells respond to internal and external cellular stressors by activating stress-response pathways that re-establish homeostasis. If homeostasis is not achieved in a timely manner, stress pathways trigger programmed cell death (apoptosis) to preserve organism integrity. A highly conserved stress pathway is the unfolded protein response (UPR), which senses excessive amounts of unfolded proteins in the ER. While a physiologically beneficial pathway, the UPR requires tight regulation to provide a beneficial outcome and avoid deleterious consequences...
May 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28499919/long-non-coding-rna-ac023115-3-suppresses-chemoresistance-of-glioblastoma-by-reducing-autophagy
#20
Binbin Ma, Zhongbo Yuan, Li Zhang, Peng Lv, Ting Yang, Jinxia Gao, Ning Pan, Qiong Wu, Jiacheng Lou, Chuanchun Han, Bo Zhang
Malignant glioma is an aggressive brain cancer that responds poorly to chemotherapy. However, the molecular mechanism underlying the development of chemoresistance in glioma is not well-understood. In this study, we show that long non-coding RNA AC023115.3 is induced by cisplatin in human glioblastoma cells and that elevated AC023115.3 promotes cisplatin-induced apoptosis by inhibiting autophagy. Further mechanistic studies revealed that AC023115.3 acts as a competing endogenous RNA for miR-26a and attenuates the inhibitory effect of miR-26a on GSK3β, a proline-directed serine-threonine kinase that promotes the degradation of Mcl1, leading to an increase in GSK3β and a decrease in autophagy...
May 9, 2017: Biochimica et Biophysica Acta
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