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https://www.readbyqxmd.com/read/28224619/fl-asparaginase-mediated-downregulation-of-c-myc-promotes-1-25-oh-2-d3-induced-myeloid-differentiation-in-acute-myeloid-leukemia-cells
#1
Ju Han Song, Eunchong Park, Myun Soo Kim, Kyung-Min Cho, Su-Ho Park, Arim Lee, Jiseon Song, Hyeoung-Joon Kim, Jeong-Tae Koh, Tae Sung Kim
Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28224429/slc38a1-promotes-proliferation-and-migration-of-human-colorectal-cancer-cells
#2
Fen-Fang Zhou, Wei Xie, Shuang-Qian Chen, Xiao-Kang Wang, Qing Liu, Xue-Kai Pan, Fei Su, Mao-Hui Feng
Current studies have demonstrated that SLC38A1 proteins play a causal role in neoplastic cell transformation. The twofold aim of this study was to provide insight into whether a variance in the expression of SLC38A1 exists between human colorectal cancer and healthy human tissues and to determine how silencing or overexpressing the SLC38A1 gene could affect the proliferation, viability and migration of colorectal cancer cells. Immunohistochemical staining was used to analyze the expression of SLC38A1 in colorectal cancer tissues and adjacent normal mucosa in 77 patients who underwent surgical resection...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28223711/identification-of-novel-cancer-therapeutic-targets-using-a-designed-and-pooled-shrna-library-screen
#3
David Oliver, Hao Ji, Piaomu Liu, Alexander Gasparian, Ellen Gardiner, Samuel Lee, Adrian Zenteno, Lillian O Perinskaya, Mengqian Chen, Phillip Buckhaults, Eugenia Broude, Michael D Wyatt, Homayoun Valafar, Edsel Peña, Michael Shtutman
Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223538/tissue-transglutaminase-induces-epithelial-mesenchymal-transition-and-the-acquisition-of-stem-cell-like-characteristics-in-colorectal-cancer-cells
#4
Oluseyi Ayinde, Zhuo Wang, Martin Griffin
Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28222440/sumo-1-gene-silencing-inhibits-proliferation-and-promotes-apoptosis-of-human-gastric-cancer-sgc-7901-cells
#5
Lifang Jin, Kexin Shen, Tong Chen, Wei Yu, Huaiyu Zhang
BACKGROUND: It has been reported that blocking small ubiquitin-like modifier (SUMO) conjugation by silencing SUMO gene remarkably decreased tumor growth in vivo. However, few studies have examined the relationship between SUMO gene silencing and gastric cancer (GC). The study aims to explore the effects of SUMO-1 gene silencing on GC cell proliferation and apoptosis. METHODS: GC cells were cultured and divided into 5 groups: the blank group (without any transfection or treatment), the empty vector group (transfected with empty vector), the shRNA-SUMO-1-1 group (transfected with shRNA-SUMO-1-1 plasmid), the shRNA-SUMO-1-2 group (transfected with shRNA-SUMO-1-2 plasmid), and the shRNA-SUMO-1-3 group (transfected with shRNA-SUMO-1-3 plasmid)...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222338/effect-of-synaptic-adhesion-like-molecule-3-on-epileptic-seizures-evidence-from-animal-models
#6
Jie Li, Ling Chen, Na Wang, Guohui Jiang, Yuqing Wu, Yi Zhang
Axonal sprouting and synaptic reorganization are the primary pathophysiological characteristics of epilepsy. Recent studies demonstrated that synaptic adhesion-like molecule 3 (SALM3) is highly expressed in the central nervous system and plays important roles in neurite outgrowth, branching, and axon guidance, mechanisms that are also observed in epilepsy. However, the expression of SALM3 in the epileptic brain and the effect of SALM3 in the pathogenesis of epilepsy remain unclear. The aims of this study were to investigate SALM3 expression in rat models of epilepsy and to explore the functional significance of SALM3 in epilepsy...
February 17, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28222148/microrna-200a-silencing-protects-neural-stem-cells-against-cerebral-ischemia-reperfusion-injury
#7
Ji Ma, Shaofeng Shui, Xinwei Han, Dong Guo, Tengfei Li, Lei Yan
Neural stem cells (NSCs) play major roles in neurological recovery after cerebral infarction (CI). This study was trying to investigate whether miR-200a, a vital regulator in cell proliferation, migration and apoptosis, also has a role in oxygen-glucose deprivation/reperfusion (OGD/R) injured NSCs. In this study, primary NSCs were subjected to OGD/R conditions to mimic an in vitro CI model. Before OGD/R induction, NSCs were transfected with vector or shRNA against miR-200a to overexpress or suppress miR-200a expression...
2017: PloS One
https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#8
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28220894/inhibition-of-n1-src-kinase-by-a-specific-sh3-peptide-ligand-reveals-a-role-for-n1-src-in-neurite-elongation-by-l1-cam
#9
Sarah Keenan, Sarah J Wetherill, Christopher I Ugbode, Sangeeta Chawla, William J Brackenbury, Gareth J O Evans
In the mammalian brain the ubiquitous tyrosine kinase, C-Src, undergoes splicing to insert short sequences in the SH3 domain to yield N1- and N2-Src. We and others have previously shown that the N-Srcs have altered substrate specificity and kinase activity compared to C-Src. However, the exact functions of the N-Srcs are unknown and it is likely that N-Src signalling events have been misattributed to C-Src because they cannot be distinguished by conventional Src inhibitors that target the kinase domain. By screening a peptide phage display library, we discovered a novel ligand (PDN1) that targets the unique SH3 domain of N1-Src and inhibits N1-Src in cells...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220838/pan-neurexin-perturbation-results-in-compromised-synapse-stability-and-a-reduction-in-readily-releasable-synaptic-vesicle-pool-size
#10
Dylan P Quinn, Annette Kolar, Michael Wigerius, Rachel N Gomm-Kolisko, Hanine Atwi, James P Fawcett, Stefan R Krueger
Neurexins are a diverse family of cell adhesion molecules that localize to presynaptic specializations of CNS neurons. Heterologous expression of neurexins in non-neuronal cells leads to the recruitment of postsynaptic proteins in contacting dendrites of co-cultured neurons, implicating neurexins in synapse formation. However, isoform-specific knockouts of either all α- or all β-neurexins show defects in synaptic transmission but an unaltered density of glutamatergic synapses, a finding that argues against an essential function of neurexins in synaptogenesis...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220828/rspo3-lgr4-regulates-osteogenic-differentiation-of-human-adipose-derived-stem-cells-via-erk-fgf-signalling
#11
Min Zhang, Ping Zhang, Yunsong Liu, Longwei Lv, Xiao Zhang, Hao Liu, Yongsheng Zhou
The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218903/macrophage-migration-inhibitory-factor-downregulation-a-novel-mechanism-of-resistance-to-anti-angiogenic-therapy
#12
B A Castro, P Flanigan, A Jahangiri, D Hoffman, W Chen, R Kuang, M De Lay, G Yagnik, J R Wagner, S Mascharak, M Sidorov, S Shrivastav, G Kohanbash, H Okada, M K Aghi
Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28217948/shrna-mediated-ablation-of-prostate-and-testis-expressed-pate-messenger-rna-results-in-impaired-sperm-function-and-fertility
#13
A Rajesh, S Yenugu
Spermatogenesis and sperm maturation are complex processes mediated by a variety of proteins present in the testicular and epididymal mileu. In the recent years, functional characterization of these proteins is being studied by genetic manipulations that involve targeted over expression or knock down of specific genes. In this study, we adopted FuGENE 6-based in vivo transfection of rat cauda epididymis with pGFP-V-RS plasmid that encodes shRNA to knock down Pate mRNA levels to implicate a possible role for this gene in sperm function...
February 19, 2017: Andrology
https://www.readbyqxmd.com/read/28216611/long-non-coding-rna-reprogramming-ror-promotes-cell-proliferation-in-colorectal-cancer-via-affecting-p53
#14
Hong Li, Xiumei Jiang, Xuemei Niu
BACKGROUND Colorectal cancer (CRC) remains one of the most common lethal malignant tumors worldwide. The correlation between lncRNAs expression and CRC development has not been well identified in the recent literature. This study focused on the role of lncRNA-ROR on CRC progression and development. MATERIAL AND METHODS Quantitative real-time PCR (qRT-PCR) assay was conducted to identify the expression level of lncRNA-ROR. Cell proliferation and viability were examined by MTT assay and colony formation assay...
February 20, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28216161/reduced-expression-of-citrate-synthase-leads-to-excessive-superoxide-formation-and-cell-apoptosis
#15
Quanxiang Cai, Mengmeng Zhao, Xiang Liu, Xiaochun Wang, Yao Nie, Ping Li, Tingyan Liu, Ruli Ge, Fengchan Han
A/J mice are a mouse model of age-related hearing loss. It has been demonstrated that a mutation in gene of citrate synthase (CS) contributes to the early onset of hearing loss occurring at about one month of age. To understand the effects of a decreased CS activity that results from the mutation in Cs gene on hearing loss in A/J mice, human kidney cell line (293T) was transiently transfected with short hairpin RNA for Cs (shRNA-Cs) to reduce expression of CS. In comparison with those of cells transfected with a scrambled sequence (shRNA-NC), the oxygen consumption rate and adenosine trisphosphate (ATP) production level were decreased in 293T cells transfected with shRNA-Cs...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28214829/ephb4-regulates-self-renewal-proliferation-and-neuronal-differentiation-of-human-embryonic-neural-stem-cells-in-vitro
#16
Tingting Liu, Xianwei Zeng, Fangling Sun, Hongli Hou, Yunqian Guan, Deyu Guo, Houxi Ai, Wen Wang, Guojun Zhang
BACKGROUND/AIMS: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. METHODS: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs...
February 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214593/jak-stat-pathway-directed-therapy-of-t-cell-leukemia-lymphoma-inspired-by-functional-and-structural-genomics
#17
REVIEW
Thomas A Waldmann
Abnormal activation of the γc cytokine JAK/STAT signaling pathway assessed by STAT3 or STAT5b phosphorylation was present in a proportion of many T-cell malignancies. Activating mutations of STAT3/STAT5b and JAK1/3 were present in some but not in all cases with constitutive signaling pathway activation. Using shRNA analysis pSTAT malignant T-cell lines were addicted to JAKs/STATs whether they were mutated or not. Activating JAK/STAT mutations were not sufficient to support leukemic cell proliferation but only augmented upstream pathway signals...
February 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28214016/melk-expression-in-ovarian-cancer-correlates-with-poor-outcome-and-its-inhibition-by-otssp167-abrogates-proliferation-and-viability-of-ovarian-cancer-cells
#18
Reto S Kohler, Henriette Kettelhack, Alexandra M Knipprath-Mészaros, André Fedier, Andreas Schoetzau, Francis Jacob, Viola Heinzelmann-Schwarz
OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis)...
February 14, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#19
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213380/complex-formation-with-pentraxin-2-regulates-factor-x-plasma-levels-and-macrophage-interactions
#20
Vincent Muczynski, Gabriel Aymé, Véronique Regnault, Marc Vasse, Delphine Borgel, Paulette Legendre, Amine Bazaa, Amélie Harel, Cécile Loubière, Peter J Lenting, Cécile V Denis, Olivier D Christophe
Recently, we have identified scavenger receptor-AI (SR-AI) as a receptor for coagulation factor X (FX), mediating the formation of a FX-reservoir at the macrophage-surface (Muczynski, Blood 2016 127:778). Here, we demonstrate that the FX/SR-AI-complex comprises a third protein, pentraxin-2. The presence of pentraxin-2 is essential to prevent internalization of FX by SR-AI, while the presence of FX is needed to interfere with internalization of pentraxin-2. Binding studies showed that FX, SR-AI and pentraxin-2 independently bind to each other (Kd,app: 0...
February 17, 2017: Blood
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