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https://www.readbyqxmd.com/read/29333089/lentivirus-mediated-shrna-targeting-cnn2-inhibits-hepatocarcinoma-in-vitro-and-in-vivo
#1
Xueqing Kang, Feng Wang, Xiuwan Lan, Xiaolong Li, Shunxin Zheng, Zhilue Lv, Yuan Zhuang, Yongxiang Zhao, Sufang Zhou
Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of mortality. Our previous study shows the expression of calponin 2 (CNN2) is up-regulated in hepatocellular carcinoma tissues, especially in metastatic ones. To better understand the role of CNN2 in HCC, RNA interference (RNAi) was used to explore its role in tumor growth and metastasis. Methods: Lentivirus-mediated CNN2-shRNA was transfected into SK-hep-1 cells, and the efficacy of CNN2 expression, cell migration, invasion, proliferation and cell cycles were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), Transwell assay, methyl thiazol tetrazolium assay and flow cytometry, respectively...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29331023/temozolomide-analog-pmx-465-downregulates-mgmt-expression-in-hct116-colorectal-carcinoma-cells
#2
Zhikuan Yang, Danping Wei, Feifei Liu, Jing Liu, Xiaoming Wu, Malcolm F G Stevens, Tracey D Bradshaw, Ying Luo, Jihong Zhang
The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29329719/regulatory-potential-of-the-rna-processing-machinery-implications-for-human-disease
#3
REVIEW
Kirstyn T Carey, Vihandha O Wickramasinghe
Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels...
January 9, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29326041/role-of-the-mrna-export-factor-sus1-in-oxidative-stress-tolerance-in-candida-albicans
#4
Chenpeng Xiao, Qilin Yu, Bing Zhang, Jianrong Li, Dan Zhang, Mingchun Li
In eukaryotes, the nuclear export of mRNAs is essential for gene expression. However, little is known about the role of mRNA nuclear export in the important fungal pathogen, Candida albicans. In this study, we identified C. albicans Sus1, a nucleus-localized protein that is required for mRNA export. Interestingly, the sus1Δ/Δ displayed hyper-sensitivity to extracellular oxidative stress, enhanced ROS accumulation and severe oxidative stress-related cell death. More strikingly, although the mutant exhibited normal activation of the expression of oxidative stress response (OSR) genes, it had attenuated activity of ROS scavenging system, which may be attributed to the defect in OSR mRNA export in this mutant...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29322325/histochemical-evidence-of-igf2-mrna-binding-protein-2-mediated-regulation-of-osteoclast-function-and-adhesive-ability
#5
Hongrui Liu, Dongfang Li, Shanshan Liu, Zhaopeng Liu, Minqi Li
Insulin-like growth factor 2 (IGF2) messenger RNA-binding proteins (IMPs) are a family of oncofetal RNA-binding proteins that play important roles in cell migration, renewal, and metabolism. IMP2 gene expression may be important in determining IGF2 levels and might, thereby, be central to bone metabolism. In our present study, IMP2-deficient mice exhibited more immature bone structures, characterized by abundant residual cartilage cores; growth plates containing more rich cartilage matrix, which was arranged irregularly; and a significantly thicker hypertrophic chondrocyte layer in the femoral metaphysis, compared with wild-type mice...
January 10, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29320459/the-landscape-of-small-non-coding-rnas-in-triple-negative-breast-cancer
#6
Yan Guo, Hui Yu, Jing Wang, Quanhu Sheng, Shilin Zhao, Ying-Yong Zhao, Brian D Lehmann
Triple-negative breast cancer (TNBC) is an operational term for breast cancers lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is, therefore, inherently heterogeneous, and is associated with worse prognosis, greater rates of metastasis, and earlier onset. TNBC displays mutational and transcriptional diversity, and distinct mRNA transcriptional subtypes exhibiting unique biology. High-throughput sequencing has extended cancer research far beyond protein coding regions that include non-coding small RNAs, such as miRNA, isomiR, tRNA, snoRNAs, snRNA, yRNA, 7SL, and 7SK...
January 10, 2018: Genes
https://www.readbyqxmd.com/read/29318513/targeted-elimination-of-mutant-mitochondrial-dna-in-melas-ipscs-by-mitotalens
#7
Yi Yang, Han Wu, Xiangjin Kang, Yanhui Liang, Ting Lan, Tianjie Li, Tao Tan, Jiangyun Peng, Quanjun Zhang, Geng An, Yali Liu, Qian Yu, Zhenglai Ma, Ying Lian, Boon Seng Soh, Qingfeng Chen, Ping Liu, Yaoyong Chen, Xiaofang Sun, Rong Li, Xiumei Zhen, Ping Liu, Yang Yu, Xiaoping Li, Yong Fan
Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m...
January 9, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29316522/joint-toxic-effects-of-triazophos-and-imidacloprid-on-zebrafish-danio-rerio
#8
Shenggan Wu, Xinfang Li, Xinju Liu, Guiling Yang, Xuehua An, Qiang Wang, Yanhua Wang
Pesticide contamination is more often found as a mixture of different pesticides in water bodies rather than individual compounds. However, regulatory risk evaluation is mostly based on the effects of individual pesticides. In the present study, we aimed to investigate the individual and joint toxicities of triazophos (TRI) and imidacloprid (IMI) to the zebrafish (Danio rerio) using acute indices and various sublethal endpoints. Results from 96-h semi-static test indicated that the LC50 values of TRI to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0...
January 6, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29314553/identification-of-mir-305-a-microrna-that-promotes-aging-and-its-target-mrnas-in-drosophila
#9
Makiko Ueda, Tetsuya Sato, Yasuyuki Ohkawa, Yoshihiro H Inoue
MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel Drosophila miRNAs involved in aging. We selected eight Drosophila miRNAs, displaying high homology with seed sequences of aging-related miRNAs characterized in other species, and investigated whether the over-expression of these miRNAs affected aging in Drosophila adult flies. The lifespan of adults over-expressing miR-305, a miRNA showing high homology with miR-239 in C. elegans, was significantly shorter...
January 5, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29314441/alterations-in-the-gut-barrier-and-involvement-of-toll-like-receptor-4-in-murine-postoperative-ileus
#10
S-S Lin, R-Q Zhang, L Shen, X-J Xu, K Li, A-V Bazhin, J Fichna, Y-Y Li
BACKGROUND: The changes in the gut barrier (GB) and associated mechanisms in postoperative ileus (POI) are still unclear. Toll-like receptor 4 (TLR4) is involved in inflammation, which may cause GB dysfunction and POI. Here, the roles of the GB in POI in relation to TLR4-dependent signaling pathways were explored. METHODS: POI was induced by small bowel manipulation in wild-type (WT) and TLR4-knockout (TLR4-/-) mice. Twenty-four hours after manipulation, indices of gastrointestinal (GI) transit, GB structure and function, inflammation, and related signaling pathways were analyzed...
January 4, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29314052/osprr37-confers-an-expanded-regulation-of-the-diurnal-rhythms-of-the-transcriptome-and-photoperiodic-flowering-pathways-in-rice
#11
Chuan Liu, Xuefeng Qu, Yanhao Zhou, Gaoyuan Song, Naghmeh Abiri, Yuhui Xiao, Fan Liang, Daiming Jiang, Zhongli Hu, Daichang Yang
The circadian clock enables organisms to rapidly adapt to the ever-changing environmental conditions that are caused by daily light/dark cycles. Circadian clock genes universally affect key agricultural traits, particularly flowering time. Here, we show that OsPRR37, a circadian clock gene, delays rice flowering time in an expression level-dependent manner. Using high-throughput mRNA sequencing (RNA-seq) on an OsPRR37 overexpressing transgenic line (OsPRR37-OE5) and the recipient parent Guangluai4 (GL) that contains the loss-of-function Osprr37, we identify 14,992 genes that display diurnal rhythms, which account for 52...
January 5, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29311466/-elaboration-of-pseudo-natural-products-using-artificial-in-vitro-biosynthesis-systems
#12
Yuki Goto
 Peptidic natural products often consist of not only proteinogenic building blocks but also unique non-proteinogenic structures such as macrocyclic scaffolds and N-methylated backbones. Since such non-proteinogenic structures are important structural motifs that contribute to diverse bioactivity, we have proposed that peptides with non-proteinogenic structures should be attractive candidates as artificial bioactive peptides mimicking natural products, or so-called pseudo-natural products. We previously devised an engineered translation system for pseudo-natural peptides, referred to as the flexible in vitro translation (FIT) system...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29311157/nkx2-8-inhibits-epithelial-mesenchymal-transition-in-bladder-urothelial-carcinoma-via-transcriptional-repression-of-twist1
#13
Chunping Yu, Zhuowei Liu, Qiuhong Chen, Yonghong Li, Lijuan Jiang, Zhiling Zhang, Fangjian Zhou
Epithelial-to-mesenchymal transition (EMT) promotes metastasis which is the main cause of bladder urothelial carcinoma (UC)-related death. Loss of the candidate tumor suppressor gene Nkx2.8 has been associated with UC lymph node metastasis. Here we show that enforced expression of Nkx2.8 is sufficient to inhibit EMT, reduce motility and blunt invasiveness of UC cells. Mechanistic investigations showed that Nkx2.8 negatively regulated expression of the EMT inducer Twist1 in UC cells, at both the level of mRNA and protein accumulation...
January 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29305862/stim1-deficiency-protects-the-liver-from-ischemia-reperfusion-injury-in-mice
#14
Yanyang Li, Chunyan Lou, Weiying Wang
Hepatic ischemia reperfusion (I/R) injury is unavoidable in various clinical conditions. Despite considerable investigation, the underlying molecular mechanism revealing liver I/R injury remains elusive. Stromal interaction molecule 1 (STIM1) plays essential role in regulating the induction of cellular responses to a number of stress conditions, including temperature changes, elevated ROS, and hypoxia. Here, to explore if STIM1 is involved in hepatic injury, wild type (WT) and STIM1-knockout (STIM1-/-) mice were subjected to I/R...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29300972/a-recurrent-de-novo-missense-mutation-in-ubtf-causes-developmental-neuroregression
#15
Camilo Toro, Roderick T Hori, May Christine V Malicdan, Cynthia J Tifft, Amy Goldstein, William A Gahl, David R Adams, Fauni Harper, Lynne A Wolfe, Jianfeng Xiao, Mohammad M Khan, Jun Tian, Kevin A Hope, Lawrence T Reiter, Michel G Tremblay, Thomas Moss, Alexis L Franks, Chris Balak, Mark S LeDoux
UBTF (upstream binding transcription factor) exists as two isoforms; UBTF1 regulates rRNA transcription by RNA polymerase 1, whereas UBTF2 regulates mRNA transcription by RNA polymerase 2. Herein, we describe 4 patients with very similar patterns of neuroregression due to recurrent de novo mutations in UBTF (GRCh37/hg19, NC_000017.10:g.42290219C>T, NM_014233.3:c.628G>A) resulting in the same amino acid change in both UBTF1 and UBTF2 (p.Glu210Lys [p.E210K]). Disease onset in our cohort was at 2.5 to 3 yrs and characterized by slow progression of global motor, cognitive and behavioral dysfunction...
January 2, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29300081/branched-hybridization-chain-reaction-bhcr-circuit-for-ultrasensitive-localizable-imaging-of-mrna-in-living-cells
#16
Lan Liu, Jin-Wen Liu, Han Wu, Xiang-Nan Wang, Ru-Qin Yu, Jian-Hui Jiang
Hybridization chain reaction (HCR) circuits are valuable approaches to monitor low-abundance mRNA, and current HCR is still subjected to issues such as limited amplification efficiency, compromised localization resolution or complicated designs. We report a novel branched HCR (bHCR) circuit for efficient signal-amplified imaging of mRNA in living cells. The bHCR can be realized using a simplified design by hierarchically coupling two HCR circuits with two split initiator fragments of the secondary HCR circuit incorporated in the probes for the primary HCR circuit...
January 4, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29297095/amphioxus-sycp1-a-case-of-retrogene-replacement-and-co-option-of-regulatory-elements-adjacent-to-the-parahox-cluster
#17
Myles G Garstang, David E K Ferrier
Retrogenes are formed when an mRNA is reverse-transcribed and reinserted into the genome in a location unrelated to the original locus. If this retrocopy inserts into a transcriptionally favourable locus and is able to carry out its original function, it can, in rare cases, lead to retrogene replacement. This involves the original, often multi-exonic, parental copy being lost whilst the newer single-exon retrogene copy 'replaces' the role of the ancestral parent gene. One example of this is amphioxus SYCP1, a gene that encodes a protein used in synaptonemal complex formation during meiosis and which offers the opportunity to examine how a retrogene evolves after the retrogene replacement event...
January 2, 2018: Development Genes and Evolution
https://www.readbyqxmd.com/read/29295935/estrogen-dependent-epigenetic-regulation-of-soluble-epoxide-hydrolase-via-dna-methylation
#18
Yang-Ming Yang, Dong Sun, Sharath Kandhi, Ghezal Froogh, Jian Zhuge, Weihua Huang, Bruce D Hammock, An Huang
To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29290954/wee1-epigenetically-modulates-5-hmc-levels-by-py37-h2b-dependent-regulation-of-idh2-gene-expression
#19
Nupam P Mahajan, Pavani Malla, Shambhavi Bhagwat, Vasundhara Sharma, Amod Sarnaik, Jongphil Kim, Shari Pilon-Thomas, Jeffery Weber, Kiran Mahajan
Epigenetic signaling networks dynamically regulate gene expression to maintain cellular homeostasis. Previously, we uncovered that WEE1 phosphorylates histone H2B at tyrosine 37 (pY37-H2B) to negatively regulate global histone transcriptional output. Although pY37-H2B is readily detected in cancer cells, its functional role in pathogenesis is not known. Herein, we show that WEE1 deposits the pY37-H2B marks within the tumor suppressor gene, isocitrate dehydrogenase 2 (IDH2), to repress transcription in multiple cancer cells, including glioblastoma multiforme (GBMs), melanoma and prostate cancer...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290003/inhibition-of-vegf-signaling-reduces-diabetes-exacerbated-brain-swelling-but-not-infarct-size-in-large-cerebral-infarction-in-mice
#20
Eunhee Kim, Jiwon Yang, Keun Woo Park, Sunghee Cho
In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain...
December 30, 2017: Translational Stroke Research
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