Publications by authors named "Jinlong Yin"

45 Publications

Analysis of electric cigarette liquid effect on mouse brain tumor growth through EGFR and ERK activation.

PLoS One 2021 8;16(9):e0256730. Epub 2021 Sep 8.

Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, South Korea.

Introduction: Recently, electric cigarettes with liquid (e-liquid) were introduced as an alternative to tobacco smoking. They were promoted as possible cessation aids and were considered to be potentially less harmful than traditional tobacco-based cigarettes. However, there is little information on the toxicants present in e-liquids and their possible carcinogenic effects.

Methods: Western blot analysis was performed to identify the protein levels of cancer progression related signal transducers. Patient-derived brain tumor cells (CSC2) were injected into mouse brains and tumor growth was then observed by performing magnetic resonance imaging (MRI) and hematoxylin and eosin (H&E) staining of the whole brain. Immunohistochemistry (IHC) staining and Immunofluorescence staining were performed to study the expression of pEGFR and pERK.

Results: Western blotting revealed that e-liquids increased pEGFR and pERK expression in a dose dependent manner. Animal experiments revealed that the e-liquid treated group had accelerated tumor growth and poor prognosis compared to the vehicle group. Histological staining showed activation of pEGFR and pERK in the e-liquid treated group.

Conclusion: Our study revealed that e-liquid activates pEGFR and pERK, leading to accelerated brain tumor growth and poor prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256730PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425573PMC
September 2021

Tuning the Elasticity of Polymersomes for Brain Tumor Targeting.

Adv Sci (Weinh) 2021 Aug 22:e2102001. Epub 2021 Aug 22.

Henan and Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, 475004, China.

Nanoformulations show great potential for delivering drugs to treat brain tumors. However, how the mechanical properties of nanoformulations affect their ultimate brain destination is still unknown. Here, a library of membrane-crosslinked polymersomes with different elasticity are synthesized to investigate their ability to effectively target brain tumors. Crosslinked polymersomes with identical particle size, zeta potential and shape are assessed, but their elasticity is varied depending on the rigidity of incorporated crosslinkers. Benzyl and oxyethylene containing crosslinkers demonstrate higher and lower Young's modulus, respectively. Interestingly, stiff polymersomes exert superior brain tumor cell uptake, excellent in vitro blood brain barrier (BBB) and tumor penetration but relatively shorter blood circulation time than their soft counterparts. These results together affect the in vivo performance for which rigid polymersomes exerting higher brain tumor accumulation in an orthotopic glioblastoma (GBM) tumor model. The results demonstrate the crucial role of nanoformulation elasticity for brain-tumor targeting and will be useful for the design of future brain targeting drug delivery systems for the treatment of brain disease.
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http://dx.doi.org/10.1002/advs.202102001DOI Listing
August 2021

Development of a Viral RdRp-Assisted Gene Silencing System and Its Application in the Identification of Host Factors of Plant (+)RNA Virus.

Front Microbiol 2021 29;12:682921. Epub 2021 Jul 29.

Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, China.

Gene silencing induced by hairpin RNA or virus infection expression is one of the major tools in genetics studies in plants. However, when dealing with essential genes, virus-induced gene silencing (VIGS) and transgenic expression of hairpin RNA could lead to plant death, while transient expression of hairpin RNA in leaves is often less competent in downregulating target gene mRNA levels. Here, we developed a transient double-stranded RNA (dsRNA) expression system assisted by a modified viral RNA-dependent RNA polymerase (RdRp) in plant leaves. We show that this system is more effective in inducing gene silencing than the intron-spliced hairpin RNA expression. Furthermore, by using this system, we tested the role of the early secretory pathway during infection of (SMV). We found that key components of the coat protein complex II vesicles are required for the multiplication of SMV. Overall, this dsRNA-based gene silencing system is effective in downregulating plant gene expression and can be used to identify host genes involved in plant-virus interactions.
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http://dx.doi.org/10.3389/fmicb.2021.682921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358433PMC
July 2021

Polymeric nanoparticle mediated inhibition of miR-21 with enhanced miR-124 expression for combinatorial glioblastoma therapy.

Biomaterials 2021 09 20;276:121036. Epub 2021 Jul 20.

Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China; Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China; Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address:

Glioblastoma (GBM) is the most common and fatal form of malignant brain tumor. Despite intensive effort, there is still no effective GBM treatment. Therefore, novel and more effective GBM therapeutic approaches are highly desired. In this study, we combined polymeric nanotechnology with microRNA (miRNA) regulation technology to develop a targeted polymeric nanoparticle to co-deliver anti-miR-21 and miR-124 into the brain to effectively treat GBM. The polymeric nanoparticle decorated with Angiopep-2 peptide not only can encapsulate miRNA via triple-interaction (electrostatic, hydrogen bond and hydrophobic bonding) to protect miRNA against enzyme degradation in the blood, but also is capable of crossing blood brain barrier (BBB) and allowing targeted delivery of miRNAs to GBM tissue due to the dual-targeting function of Angiopep-2. Moreover, the co-delivered anti-miR-21 and miR-124 simultaneously regulated the mutant RAS/PI3K/PTEN/AKT signaling pathway in tumor cells, consequently achieving combinatorial GBM therapy. This combinatorial effect was confirmed by our results showing that these miRNA nanomedicines can effectively reduce tumor cell proliferation, migration and invasion as well as reducing tumor angiogenesis. Consequently, effective suppression of tumor growth and significantly improved medium survival time are observed when these miRNA nanomedicines were assessed in an orthotopic GBM xenograft model. This work indicated that our new polymeric nanoparticles successfully mediate inhibition of miR-21 and miR-124 supplementation to significantly reduce tumorigenesis, and may have strong potential in GBM therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121036DOI Listing
September 2021

A cell wall-localized NLR confers resistance to Soybean mosaic virus by recognizing viral-encoded cylindrical inclusion protein.

Mol Plant 2021 Jul 21. Epub 2021 Jul 21.

National Center for Soybean Improvement, National Key Laboratory for Crop Genetics and Germplasm Enhancement, Key Laboratory of Biology and Genetic Improvement of Soybean-Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China. Electronic address:

Soybean mosaic virus (SMV) causes severe yield losses and seed quality reduction in soybean (Glycine max) production worldwide. Rsc4 from cultivar Dabaima is a dominant genetic locus for SMV resistance, and its mapping interval contains three nucleotide-binding domain leucine-rich repeat-containing (NLR) candidates (Rsc4-1, Rsc4-2, and Rsc4-3). The NLR-type resistant proteins were considered as important intracellular pathogen sensors in the previous studies. In this study, based on transient expression assay in Nicotiana benthamiana leaves, we found that the longest transcript of Rsc4-3 is sufficient to confer resistance to SMV, and CRISPR/Cas9-mediated editing of Rsc4-3 in resistant cultivar Dabaima compromised the resistance. Interestingly, Rsc4-3 encodes a cell-wall-localized NLR-type resistant protein. We found that the internal polypeptide region responsible for apoplastic targeting of Rsc4-3 and the putative palmitoylation sites on the N terminus are essential for the resistance. Furthermore, we showed that viral-encoded cylindrical inclusion (CI) protein partially localizes to the cell wall and can interact with Rsc4-3. Virus-driven or transient expression of CI protein of avirulent SMV strains is enough to induce resistance response in the presence of Rsc4-3, suggesting that CI is the avirulent gene for Rsc4-3-mediated resistance. Taken together, our work identified a unique NLR that recognizes plant virus in the apoplast, and provided a simple and effective method for identifying resistant genes against SMV infection.
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http://dx.doi.org/10.1016/j.molp.2021.07.013DOI Listing
July 2021

Impact of the gas dynamics on the cluster flux in a magnetron cluster-source: Influence of the chamber shape and gas-inlet position.

Rev Sci Instrum 2021 Mar;92(3):033901

Quantum Solid-State Physics, Department of Physics and Astronomy, KU Leuven, B-3001 Leuven, Belgium.

Although producing clusters by physical methods offers many benefits, low deposition rates have prevented cluster-beam deposition techniques from being adopted more widely. The influence of the gas aerodynamics inside the condensation chamber of a magnetron cluster-source on the cluster throughput is reported, leading to an improved understanding of the influence of gas aerodynamics on cluster transport. In the first part of this paper, the influence of the carrier gas's inlet position on the cluster flux is studied. In particular, two inlet configurations were investigated, i.e., from the rear of the chamber and from within the magnetron sputtering source. It was found experimentally that the latter configuration can lead to an increased cluster flux, under the same conditions of gas pressure and power applied to the magnetron. This behavior is explained with the help of simulations. In the second part of this paper, the gas dynamics behavior inside four chamber shapes, namely, two cylindrical shapes with different cross-sectional diameters and two conical shapes with different apex angles, was simulated. The modeling showed that the fraction of clusters successfully leaving the aggregation zone can be increased by up to eight times from the worst to the best performing chamber geometries studied. Finally, the cluster throughput was determined experimentally using a quartz microbalance in two of the four chamber designs. It was found that the cluster flux increased up to one order of magnitude, reaching ∼20 mg/h for a condensation chamber with a smaller cross section and a conical exit.
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http://dx.doi.org/10.1063/5.0028854DOI Listing
March 2021

Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.

Brain 2021 03;144(2):636-654

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.
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http://dx.doi.org/10.1093/brain/awaa408DOI Listing
March 2021

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma.

Genome Biol 2020 08 26;21(1):216. Epub 2020 Aug 26.

Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages.

Results: We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCO TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCO TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate the origination of MA-TAMs from peripheral blood, as well as their potential association with tumor-induced polarization states and immunosuppressive environments.

Conclusions: Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.
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http://dx.doi.org/10.1186/s13059-020-02140-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448990PMC
August 2020

ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages.

Nat Commun 2020 06 12;11(1):2978. Epub 2020 Jun 12.

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.

The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E (PGE), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.
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http://dx.doi.org/10.1038/s41467-020-16789-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293269PMC
June 2020

Evaluation of nanomechanical properties of hyperbranched polyglycerols as prospective cell membrane engineering block.

Colloids Surf B Biointerfaces 2020 Jun 17;190:110968. Epub 2020 Mar 17.

School of Life Sciences, Henan University, Kaifeng, Henan Province, 475004, China. Electronic address:

Owing to the excellent biocompatibility, hyperbranched polyglycerols (hbPGs) are one of the most promising polymers and widely employed in drug delivery. Presented as an excellent bioinert coating material, hbPGs can significantly improve the biosafety of biomedical nanomaterials. However, it is still unclear what specific properties of hbPGs are the key effectors to bioinertness. Here, atomic force microscopy was employed to test the Young's modulus and adhesion of hbPGs, spin-coated onto mica substrate. High Young's modulus indicated that the hbPGs cannot be further compressed and low adhesion implied that it is not easy to form hbPGs aggregators. This could owe to the intramolecular hydrogen bond. Morphology characterization of hbPGs self-assembled monolayer onto Si(100) substrate, confirmed the lower adhesion among different hbPGs and indicated their biofouling properties. Further confocal laser microscopy of cell membrane modified with alkyl chain (C18)-modified hbPGs and hbPGs-NH, confirmed that the antifouling properties of hbPGs are determined by terminal glycerol units. Our findings demonstrated that only hbPGs with entire terminal surface can be used as perspective cell membrane modification skeleton.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110968DOI Listing
June 2020

Charge Conversional Biomimetic Nanocomplexes as a Multifunctional Platform for Boosting Orthotopic Glioblastoma RNAi Therapy.

Nano Lett 2020 03 7;20(3):1637-1646. Epub 2020 Feb 7.

Henan-Macquarie Uni Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan 475004, China.

Nanotechnology-based RNA interference (RNAi) has shown great promise in overcoming the limitations of traditional clinical treatments for glioblastoma (GBM). However, because of the complexity of brain physiology, simple blood-brain barrier (BBB) penetration or tumor-targeting strategies cannot entirely meet the demanding requirements of different therapeutic delivery stages. Herein, we developed a charge conversional biomimetic nanoplatform with a three-layer core-shell structure to programmatically overcome persistent obstacles in siRNA delivery to GBM. The resulting nanocomplex presents good biocompatibility, prolonged blood circulation, high BBB transcytosis, effective tumor accumulation, and specific uptake by tumor cells in the brain. Moreover, red blood cell membrane (RBCm) disruption and effective siRNA release can be further triggered elegantly by charge conversion from negative to positive in the endo/lysosome (pH 5.0-6.5) of tumor cells, leading to highly potent target-gene silencing with a strong anti-GBM effect. Our study provides an intelligent biomimetic nanoplatform tailored for systemically siRNA delivery to GBM, leveraging Angiopep-2 peptide-modified, immune-free RBCm and charge conversional components. Improved therapeutic efficacy, higher survival rates, and minimized systemic side effects were achieved in orthotopic U87MG-luc human glioblastoma tumor-bearing nude mice.
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http://dx.doi.org/10.1021/acs.nanolett.9b04683DOI Listing
March 2020

A DnaJ protein that interacts with soybean mosaic virus coat protein serves as a key susceptibility factor for viral infection.

Virus Res 2020 05 18;281:197870. Epub 2020 Jan 18.

National Center for Soybean Improvement, National Key Laboratory for Crop Genetics and Germplasm Enhancement, Key Laboratory of Biology and Genetic Improvement of Soybean, Ministry of Agriculture, Nanjing Agricultural University, Weigang 1, Nanjing, China. Electronic address:

Soybean mosaic virus (SMV)-disease is one of the most serious and widespread diseases in soybean (Glycine max). In the present study, a DnaJ protein in soybean designated GmCPIP (SMV coat protein-interacting protein) was screened by the QIS-Seq (quantitative interactor screening with next-generation sequencing) method, and the interaction between SMV CP and GmCPIP was confirmed by the yeast two-hybrid (Y2H) system and bimolecular fluorescence complementation (BiFC) assay. Subcellular localization analysis indicated that both proteins are localized in the cytoplasm, cytomembrane and nucleus. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that infection with SMV-SC4 temporarily increased the transcription of GmCPIP. Virus-induced gene silencing (VIGS) down-regulated the GmCPIP gene by 82%, and the accumulation of SMV was decreased by 88.6% in GmCPIP-silenced plants inoculated with SMV-SC4. The interaction of GmCPIP with SMV CP seems to contribute to SMV infection in soybean.
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http://dx.doi.org/10.1016/j.virusres.2020.197870DOI Listing
May 2020

Phosphoserine Phosphatase Promotes Lung Cancer Progression through the Dephosphorylation of IRS-1 and a Noncanonical L-Serine-Independent Pathway.

Mol Cells 2019 Aug;42(8):604-616

Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.

Phosphoserine phosphatase (PSPH) is one of the key enzymes of the L-serine synthesis pathway. PSPH is reported to affect the progression and survival of several cancers in an L-serine synthesis-independent manner, but the mechanism remains elusive. We demonstrate that PSPH promotes lung cancer progression through a noncanonical L-serine-independent pathway. PSPH was significantly associated with the prognosis of lung cancer patients and regulated the invasion and colony formation of lung cancer cells. Interestingly, L-serine had no effect on the altered invasion and colony formation by PSPH. Upon measuring the phosphatase activity of PSPH on a serine-phosphorylated peptide, we found that PSPH dephosphorylated phospho-serine in peptide sequences. To identify the target proteins of PSPH, we analyzed the protein phosphorylation profile and the PSPH-interacting protein profile using proteomic analyses and found one putative target protein, IRS-1. Immunoprecipitation and immunoblot assays validated a specific interaction between PSPH and IRS1 and the dephosphorylation of phospho-IRS-1 by PSPH in lung cancer cells. We suggest that the specific interaction and dephosphorylation activity of PSPH have novel therapeutic potential for lung cancer treatment, while the metabolic activity of PSPH, as a therapeutic target, is controversial.
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http://dx.doi.org/10.14348/molcells.2019.0160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715339PMC
August 2019

ROS-Responsive Polymeric siRNA Nanomedicine Stabilized by Triple Interactions for the Robust Glioblastoma Combinational RNAi Therapy.

Adv Mater 2019 Sep 26;31(37):e1903277. Epub 2019 Jul 26.

Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China.

Small interfering RNA (siRNA) holds inherent advantages and great potential for treating refractory diseases. However, lack of suitable siRNA delivery systems that demonstrate excellent circulation stability and effective at-site delivery ability is currently impeding siRNA therapeutic performance. Here, a polymeric siRNA nanomedicine ([email protected]) stabilized by triple interactions (electrostatic, hydrogen bond, and hydrophobic) is constructed. Incorporating extra hydrogen and hydrophobic interactions significantly improves the physiological stability compared to an siRNA nanomedicine analog that solely relies on the electrostatic interaction for stability. The developed [email protected] nanomedicine demonstrates effective at-site siRNA release resulting from tumoral reactive oxygen species (ROS)-triggered sequential destabilization. Furthermore, the utility of [email protected] for treating glioblastoma (GBM) by functionalizing [email protected] nanomedicine with angiopep-2 peptide is enhanced. The targeted [email protected] exhibits superb blood-brain barrier penetration and potent tumor accumulation. Moreover, by cotargeting polo-like kinase 1 and vascular endothelial growth factor receptor-2, [email protected] shows effective suppression of tumor growth and significantly improved survival time of nude mice bearing orthotopic GBM brain tumors. New siRNA nanomedicines featuring triple-interaction stabilization together with inbuilt self-destruct delivery ability provide a robust and potent platform for targeted GBM siRNA therapy, which may have utility for RNA interference therapy of other tumors or brain diseases.
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http://dx.doi.org/10.1002/adma.201903277DOI Listing
September 2019

Discovery of the Agrobacterium growth inhibition sequence in virus and its application to recombinant clone screening.

AMB Express 2019 Jul 24;9(1):116. Epub 2019 Jul 24.

National Center for Soybean Improvement, National Key Laboratory for Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Weigang 1, Nanjing, 210095, People's Republic of China.

Infectious clone vectors used widely in genetic research. While constructing soybean mosaic virus (SMV) clone vectors, we found that transformed Agrobacterium grew significantly different depending on the viral strains used. In particular, the clone vectors constructed with SMV SC15 significantly suppressed the growth of Agrobacterium. Recombinant and truncated virus vector experiments showed that the polymorphism of a P1 protein coding sequence of SC15 leads to the growth inhibition of Agrobacterium. But the lack of other protein encoding sequences, except for the sequence encoding coat protein, should reduce the ability of SC15 to suppress Agrobacterium growth. A vector (pCB301-attL-SC15P) compatible with the Gateway cloning system was constructed using this Agrobacterium inhibitory sequence. The results from the LR recombination reaction with pCB301-attL-SC15P and Agrobacterium transformation showed the valuable application potential of the Agrobacterium inhibitory sequence to serve as a negative screening factor for effective recombinant clone screening in Agrobacterium.
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http://dx.doi.org/10.1186/s13568-019-0840-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656845PMC
July 2019

Interplay between TRAP1 and Sirtuin-3 Modulates Mitochondrial Respiration and Oxidative Stress to Maintain Stemness of Glioma Stem Cells.

Cancer Res 2019 04 25;79(7):1369-1382. Epub 2019 Jan 25.

Department of Biological Sciences, Ulsan National Institutes of Science and Technology (UNIST), Ulsan, Republic of Korea.

Glioblastoma (GBM) cancer stem cells (CSC) are primarily responsible for metastatic dissemination, resistance to therapy, and relapse of GBM, the most common and aggressive brain tumor. Development and maintenance of CSCs require orchestrated metabolic rewiring and metabolic adaptation to a changing microenvironment. Here, we show that cooperative interplay between the mitochondrial chaperone TRAP1 and the major mitochondria deacetylase sirtuin-3 (SIRT3) in glioma stem cells (GSC) increases mitochondrial respiratory capacity and reduces production of reactive oxygen species. This metabolic regulation endowed GSCs with metabolic plasticity, facilitated adaptation to stress (particularly reduced nutrient supply), and maintained "stemness." Inactivation of TRAP1 or SIRT3 compromised their interdependent regulatory mechanisms, leading to metabolic alterations, loss of stemness, and suppression of tumor formation by GSC . Thus, targeting the metabolic mechanisms regulating interplay between TRAP1 and SIRT3 may provide a novel therapeutic option for intractable patients with GBM. SIGNIFICANCE: Discovery and functional analysis of a TRAP1-SIRT3 complex in glioma stem cells identify potential target proteins for glioblastoma treatment.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2558DOI Listing
April 2019

Performance of Preformed Au/Cu Nanoclusters Deposited on MgO Powders in the Catalytic Reduction of 4-Nitrophenol in Solution.

Small 2018 03 7;14(13):e1703734. Epub 2018 Feb 7.

College of Engineering, Swansea University, Bay Campus, Fabian Way, Swansea, SA1 8EN, UK.

The deposition of preformed nanocluster beams onto suitable supports represents a new paradigm for the precise preparation of heterogeneous catalysts. The performance of the new materials must be validated in model catalytic reactions. It is shown that gold/copper (Au/Cu) nanoalloy clusters (nanoparticles) of variable composition, created by sputtering and gas phase condensation before deposition onto magnesium oxide powders, are highly active for the catalytic reduction of 4-nitrophenol in solution at room temperature. Au/Cu bimetallic clusters offer decreased catalyst cost compared with pure Au and the prospect of beneficial synergistic effects. Energy-dispersive X-ray spectroscopy coupled with aberration-corrected scanning transmission electron microscopy imaging confirms that the Au/Cu bimetallic clusters have an alloy structure with Au and Cu atoms randomly located. Reaction rate analysis shows that catalysts with approximately equal amounts of Au and Cu are much more active than Au-rich or Cu-rich clusters. Thus, the interplay between the Au and Cu atoms at the cluster surface appears to enhance the catalytic activity substantially, consistent with model density functional theory calculations of molecular binding energies. Moreover, the physically deposited clusters with Au/Cu ratio close to 1 show a 25-fold higher activity than an Au/Cu reference sample made by chemical impregnation.
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http://dx.doi.org/10.1002/smll.201703734DOI Listing
March 2018

Inhibition of ID1-BMPR2 Intrinsic Signaling Sensitizes Glioma Stem Cells to Differentiation Therapy.

Clin Cancer Res 2018 01 5;24(2):383-394. Epub 2017 Dec 5.

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.

Normal stem cells tightly control self-renewal and differentiation during development, but their neoplastic counterparts, cancer stem cells (CSCs), sustain tumorigenicity both through aberrant activation of stemness and evasion of differentiation. Although regulation of CSC stemness has been extensively studied, the molecular mechanisms suppressing differentiation remain unclear. We performed screening and validation studies through Western blotting, qRT-PCR for treatment of WNT and SHH signaling inhibitors, and BMP signaling inducer with control and ID1-overexpressing cells. We also performed drug treatment assays with Balb/c nude mice. Inhibitor of differentiation 1 (ID1) abrogated differentiation signals from bone morphogenetic protein receptor (BMPR) signaling in glioblastoma stem cells (GSCs) to promote self-renewal. ID1 inhibited BMPR2 expression through miRNAs, miR-17 and miR-20a, which are transcriptional targets of MYC. ID1 increases MYC expression by activating WNT and SHH signaling. Combined pharmacologic blockade of WNT and SHH signaling with BMP treatment significantly suppressed GSC self-renewal and extended survival of tumor-bearing mice. Collectively, our results suggested that ID1 simultaneously regulates stemness through WNT and SHH signaling and differentiation through BMPR-mediated differentiation signaling in GSCs, informing a novel therapeutic strategy of combinatorial targeting of stemness and differentiation. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1529DOI Listing
January 2018

Fine-mapping and identifying candidate genes conferring resistance to Soybean mosaic virus strain SC20 in soybean.

Theor Appl Genet 2018 Feb 27;131(2):461-476. Epub 2017 Nov 27.

Soybean Research Institute, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China.

Key Message: The Mendelian gene conferring resistance to Soybean mosaic virus Strain SC20 in soybean was fine-mapped onto a 79-kb segment on Chr.13 where two closely linked candidate genes were identified and qRT-PCR verified. Soybean mosaic virus (SMV) threatens the world soybean production, particularly in China. A country-wide SMV strain system composed of 22 strains was established in China, among which SC20 is a dominant strain in five provinces in Southern China. Resistance to SC20 was evaluated in parents, F, F and the F RIL (recombinant inbred line) population derived from a cross between Qihuang-1 (resistant) and NN1138-2 (susceptible). The segregation ratio of resistant to susceptible in the populations suggested a single dominant gene involved in the resistance to SC20 in Qihuang-1. A "partial genome mapping strategy" was used to map the resistance gene on Chromosome 13. Linkage analysis between 178 RILs and genetic markers showed that the SC20-resistance gene located at 3.9 and 3.8 cM to the flanking markers BARCSOYSSR_13_1099 and BARCSOYSSR_13_1185 on Chromosome 13. Subsequently, a residual heterozygote segregating population with 346 individuals was developed by selfing four plants heterozygous at markers adjacent to the tentative SC20-resistance gene; then, the candidate region was delimited to a genomic interval of approximately 79 kb flanked by the new markers gm-ssr_13-14 and gm-indel_13-3. Among the seven annotated candidate genes in this region, two genes, Glyma.13G194700 and Glyma.13G195100, encoding Toll Interleukin Receptor-nucleotide-binding-leucine-rich repeat resistance proteins were identified as candidate resistance genes by quantitative real-time polymerase chain reaction and sequence analysis. The two closely linked genes work together to cause the phenotypic segregation as a single Mendelian gene. These results will facilitate marker-assisted selection, gene cloning and breeding for the resistance to SC20.
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http://dx.doi.org/10.1007/s00122-017-3014-1DOI Listing
February 2018

Inhibition of BMP signaling overcomes acquired resistance to cetuximab in oral squamous cell carcinomas.

Cancer Lett 2018 02 15;414:181-189. Epub 2017 Nov 15.

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea; Rare Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea; Oral Oncology Clinic, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea. Electronic address:

Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that bone morphogenic protein-7-phosphorylated Smad-1, -5, -8 (BMP7-p-Smad1/5/8) signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of p-Smad1/5/8. Treatment with the bone morphogenic protein receptor type 1 (BMPRI) inhibitor, DMH1 significantly reduced cetuximab-resistant OSCC tumor growth, and combined treatment of DMH1 and cetuximab remarkably reduced relapsed tumor growth in vivo. Importantly, p-Smad1/5/8 level was elevated in cetuximab-resistant patients and this correlated with poor prognosis. Collectively, our results indicate that the BMP7-p-Smad1/5/8 signaling is a key pathway to acquired cetuximab resistance, and demonstrate that combination therapy of cetuximab and a BMP signaling inhibitor as potentially a new therapeutic strategy for overcoming acquired resistance to cetuximab in OSCC.
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http://dx.doi.org/10.1016/j.canlet.2017.11.013DOI Listing
February 2018

Fine-mapping and identification of a novel locus Rsc15 underlying soybean resistance to Soybean mosaic virus.

Theor Appl Genet 2017 Nov 19;130(11):2395-2410. Epub 2017 Aug 19.

National Center for Soybean Improvement, Key Laboratory of Biology and Genetic Improvement of Soybean, Ministry of Agriculture, Nanjing, People's Republic of China.

Key Message: Rsc15, a novel locus underlying soybean resistance to SMV, was fine mapped to a 95-kb region on chromosome 6. The Rsc15- mediated resistance is likely attributed to the gene GmPEX14 , the relative expression of which was highly correlated with the accumulation of H O along with the activities of POD and CAT during the early stages of SMV infection in RN-9. Soybean mosaic virus (SMV) causes severe yield losses and seed quality deterioration in soybean [Glycine max (L.) Merr.] worldwide. A series of single dominant SMV resistance genes have been identified on respective soybean chromosomes 2, 13 and 14, while one novel locus, Rsc15, underlying resistance to the virulent SMV strain SC15 from soybean cultivar RN-9 has been recently mapped to a 14.6-cM region on chromosome 6. However, candidate gene has not yet been identified within this region. In the present study, we aimed to fine map the Rsc15 region and identify candidate gene(s) for this invaluable locus. High-resolution fine-mapping revealed that the Rsc15 gene was located in a 95-kb genomic region which was flanked by the two simple sequence repeat (SSR) markers SSR_06_17 and BARCSOYSSR_06_0835. Allelic sequence comparison and expression profile analysis of candidate genes inferred that the gene Glyma.06g182600 (designated as GmPEX14) was the best candidate gene attributing for the resistance of Rsc15, and that genes encoding receptor-like kinase (RLK) (i.e., Glyma.06g175100 and Glyma.06g184400) and serine/threonine kinase (STK) (i.e., Glyma.06g182900 and Glyma.06g183500) were also potential candidates. High correlations were established between the relative expression level of GmPEX14 and the hydrogen peroxide (HO) concentration and activities of catalase (CAT) and peroxidase (POD) during the early stages of SMV-SC15 infection in RN-9. The results of the present study will be useful in marker-assisted breeding for SMV resistance and will lead to further understanding of the molecular mechanisms of host resistance against SMV.
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http://dx.doi.org/10.1007/s00122-017-2966-5DOI Listing
November 2017

Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C/EBPβ Signaling.

Cancer Res 2017 09 28;77(18):4973-4984. Epub 2017 Jul 28.

Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-0388DOI Listing
September 2017

TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling.

Oncotarget 2016 Nov;7(48):79854-79868

Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi, Korea.

TRIM71 (tripartite motif-containing 71) belongs to the TRIM-NHL protein family, which plays a conserved role in regulating early development and differentiation. However, the molecular functions of TRIM71 have remained largely unknown. Here, we explored the role of TRIM71 together with modulation of Lin28B-let-7-HMGA2 (high-mobility group AT-hook 2) signaling in tumorigenesis. TRIM71 overexpression opposed Lin28B-induced transformation in primary cells and inhibited tumor formation in a mouse model. Specific knockdown of TRIM71 expression increased cancer cell proliferation and invasion. Conversely, overexpression of wild-type TRIM71 in non-small cell lung carcinoma (NSCLC) cells in which Lin28B-let-7-HMGA2 signaling was conserved decreased both cancer cell phenotypes. More importantly, overexpression of an ubiquitin transfer activity-deficient TRIM71 mutant in NSCLC cells had no effect on proliferation or invasion, regardless of the conservation status of Lin28B-let-7-HMGA2 signaling. The tumorigenic inhibitory action of TRIM71 was antagonized by overexpression of the TRIM71 downstream targets, Lin28B and HMGA2. Furthermore, a bioinformatics analysis revealed that TRIM71 expression was downregulated in various types of cancer tissue from patients. Taken together, these data indicate that TRIM71 acts through post-transcriptional repression of Lin28B and subsequent modulation of let-7-HMGA2 signaling during tumorigenesis to potentially function as a tumor suppressor.
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http://dx.doi.org/10.18632/oncotarget.13036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346756PMC
November 2016

Enhancement of the Hydrogen Evolution Reaction from Ni-MoS Hybrid Nanoclusters.

ACS Catal 2016 Sep 2;6(9):6008-6017. Epub 2016 Aug 2.

Nanoscale Physics Research Laboratory, School of Physics and Astronomy, University of Birmingham , Birmingham B15 2TT, United Kindgom.

This report focuses on a novel strategy for the preparation of transition metal-MoS hybrid nanoclusters based on a one-step, dual-target magnetron sputtering, and gas condensation process demonstrated for Ni-MoS. Aberration-corrected STEM images coupled with EDX analysis confirms the presence of Ni and MoS in the hybrid nanoclusters (average diameter = 5.0 nm, Mo:S ratio = 1:1.8 ± 0.1). The Ni-MoS nanoclusters display a 100 mV shift in the hydrogen evolution reaction (HER) onset potential and an almost 3-fold increase in exchange current density compared with the undoped MoS nanoclusters, the latter effect in agreement with reported DFT calculations. This activity is only reached after air exposure of the Ni-MoS hybrid nanoclusters, suggested by XPS measurements to originate from a Ni dopant atoms oxidation state conversion from metallic to 2+ characteristic of the NiO species active to the HER. Anodic stripping voltammetry (ASV) experiments on the Ni-MoS hybrid nanoclusters confirm the presence of Ni-doped edge sites and reveal distinctive electrochemical features associated with both doped Mo-edge and doped S-edge sites which correlate with both their thermodynamic stability and relative abundance.
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http://dx.doi.org/10.1021/acscatal.6b01274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5089059PMC
September 2016

The ID1-CULLIN3 Axis Regulates Intracellular SHH and WNT Signaling in Glioblastoma Stem Cells.

Cell Rep 2016 08 28;16(6):1629-1641. Epub 2016 Jul 28.

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea. Electronic address:

Inhibitor of differentiation 1 (ID1) is highly expressed in glioblastoma stem cells (GSCs). However, the regulatory mechanism responsible for its role in GSCs is poorly understood. Here, we report that ID1 activates GSC proliferation, self-renewal, and tumorigenicity by suppressing CULLIN3 ubiquitin ligase. ID1 induces cell proliferation through increase of CYCLIN E, a target molecule of CULLIN3. ID1 overexpression or CULLIN3 knockdown confers GSC features and tumorigenicity to murine Ink4a/Arf-deficient astrocytes. Proteomics analysis revealed that CULLIN3 interacts with GLI2 and DVL2 and induces their degradation via ubiquitination. Consistent with ID1 knockdown or CULLIN3 overexpression in human GSCs, pharmacologically combined control of GLI2 and β-CATENIN effectively diminishes GSC properties. A ID1-high/CULLIN3-low expression signature correlates with a poor patient prognosis, supporting the clinical relevance of this signaling axis. Taken together, a loss of CULLIN3 represents a common signaling node for controlling the activity of intracellular WNT and SHH signaling pathways mediated by ID1.
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http://dx.doi.org/10.1016/j.celrep.2016.06.092DOI Listing
August 2016

The cluster beam route to model catalysts and beyond.

Faraday Discuss 2016 07;188:39-56

Nanoscale Physics Research Laboratory, School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT, UK.

The generation of beams of atomic clusters in the gas phase and their subsequent deposition (in vacuum) onto suitable catalyst supports, possibly after an intermediate mass filtering step, represents a new and attractive approach for the preparation of model catalyst particles. Compared with the colloidal route to the production of pre-formed catalytic nanoparticles, the nanocluster beam approach offers several advantages: the clusters produced in the beam have no ligands, their size can be selected to arbitrarily high precision by the mass filter, and metal particles containing challenging combinations of metals can be readily produced. However, until now the cluster approach has been held back by the extremely low rates of metal particle production, of the order of 1 microgram per hour. This is more than sufficient for surface science studies but several orders of magnitude below what is desirable even for research-level reaction studies under realistic conditions. In this paper we describe solutions to this scaling problem, specifically, the development of two new generations of cluster beam sources, which suggest that cluster beam yields of grams per hour may ultimately be feasible. Moreover, we illustrate the effectiveness of model catalysts prepared by cluster beam deposition onto agitated powders in the selective hydrogenation of 1-pentyne (a gas phase reaction) and 3-hexyn-1-ol (a liquid phase reaction). Our results for elemental Pd and binary PdSn and PdTi cluster catalysts demonstrate favourable combinations of yield and selectivity compared with reference materials synthesised by conventional methods.
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http://dx.doi.org/10.1039/c5fd00178aDOI Listing
July 2016

DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis.

Brain 2015 Sep 29;138(Pt 9):2553-70. Epub 2015 Jun 29.

1 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea 3 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Republic of Korea

Upregulation of microRNA-21 (miR-21) is known to be strongly associated with the proliferation, invasion, and radio-resistance of glioma cells. However, the regulatory mechanism that governs the biogenesis of miR-21 in glioma is still unclear. Here, we demonstrate that the DEAD-box RNA helicase, DDX23, promotes miR-21 biogenesis at the post-transcriptional level. The expression of DDX23 was enhanced in glioma tissues compared to normal brain, and expression level of DDX23 was highly associated with poor survival of glioma patients. Specific knockdown of DDX23 expression suppressed glioma cell proliferation and invasion in vitro and in vivo, which is similar to the function of miR-21. We found that DDX23 increased the level of miR-21 by promoting primary-to-precursor processing of miR-21 through an interaction with the Drosha microprocessor. Mutagenesis experiments critically demonstrated that the helicase activity of DDX23 was essential for the processing (cropping) of miR-21, and we further found that ivermectin, a RNA helicase inhibitor, decreased miR-21 levels by potentially inhibiting DDX23 activity and blocked invasion and cell proliferation. Moreover, treatment of ivermectin decreased glioma growth in mouse xenografts. Taken together, these results suggest that DDX23 plays an essential role in glioma progression, and might thus be a potential novel target for the therapeutic treatment of glioma.
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http://dx.doi.org/10.1093/brain/awv167DOI Listing
September 2015

Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells.

PLoS Biol 2015 May 20;13(5):e1002152. Epub 2015 May 20.

Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea; Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea.

Epidermal growth factor receptor variant III (EGFRvIII) has been associated with glioma stemness, but the direct molecular mechanism linking the two is largely unknown. Here, we show that EGFRvIII induces the expression and secretion of pigment epithelium-derived factor (PEDF) via activation of signal transducer and activator of transcription 3 (STAT3), thereby promoting self-renewal and tumor progression of glioma stem cells (GSCs). Mechanistically, PEDF sustained GSC self-renewal by Notch1 cleavage, and the generated intracellular domain of Notch1 (NICD) induced the expression of Sox2 through interaction with its promoter region. Furthermore, a subpopulation with high levels of PEDF was capable of infiltration along corpus callosum. Inhibition of PEDF diminished GSC self-renewal and increased survival of orthotopic tumor-bearing mice. Together, these data indicate the novel role of PEDF as a key regulator of GSC and suggest clinical implications.
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http://dx.doi.org/10.1371/journal.pbio.1002152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439169PMC
May 2015

The complete chloroplast genome provides insight into the evolution and polymorphism of Panax ginseng.

Front Plant Sci 2014 14;5:696. Epub 2015 Jan 14.

CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences Beijing, China.

Panax ginseng C.A. Meyer (P. ginseng) is an important medicinal plant and is often used in traditional Chinese medicine. With next generation sequencing (NGS) technology, we determined the complete chloroplast genome sequences for four Chinese P. ginseng strains, which are Damaya (DMY), Ermaya (EMY), Gaolishen (GLS), and Yeshanshen (YSS). The total chloroplast genome sequence length for DMY, EMY, and GLS was 156,354 bp, while that for YSS was 156,355 bp. Comparative genomic analysis of the chloroplast genome sequences indicate that gene content, GC content, and gene order in DMY are quite similar to its relative species, and nucleotide sequence diversity of inverted repeat region (IR) is lower than that of its counterparts, large single copy region (LSC) and small single copy region (SSC). A comparison among these four P. ginseng strains revealed that the chloroplast genome sequences of DMY, EMY, and GLS were identical and YSS had a 1-bp insertion at base 5472. To further study the heterogeneity in chloroplast genome during domestication, high-resolution reads were mapped to the genome sequences to investigate the differences at the minor allele level; 208 minor allele sites with minor allele frequencies (MAF) of ≥0.05 were identified. The polymorphism site numbers per kb of chloroplast genome sequence for DMY, EMY, GLS, and YSS were 0.74, 0.59, 0.97, and 1.23, respectively. All the minor allele sites located in LSC and IR regions, and the four strains showed the same variation types (substitution base or indel) at all identified polymorphism sites. Comparison results of heterogeneity in the chloroplast genome sequences showed that the minor allele sites on the chloroplast genome were undergoing purifying selection to adapt to changing environment during domestication process. A study of P. ginseng chloroplast genome with particular focus on minor allele sites would aid in investigating the dynamics on the chloroplast genomes and different P. ginseng strains typing.
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http://dx.doi.org/10.3389/fpls.2014.00696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294130PMC
February 2015
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