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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 469 records · Page 26
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Highly expressed lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/β-catenin signaling

Glioma is the most common and aggressive primary brain tumor in adults. Long-non coding RNAs (lncRNAs) have been recently shown to play important roles in regulating numerous biological processes both in physiologic and pathologic condition. However, the role of lncRNAs in glioma remains largely unknown. In this study, we firstly found that lncRNA CCND2-AS2 is significantly up regulated in malignant glioma tissues and cell lines. Both loss- and gain-functions assays show that CCND2-AS1 promotes glioma cells proliferation and growth. In addition, we also revealed that highly expressed CCND2-AS1 could enhance Wnt/β-catenin signaling in glioma. Taken together, our findings revealed a novel lncRNA CCND2-AS1 promotes glioma cell proliferation through Wnt/β-catenin signaling and CCND2-AS1 might function as a potential novel therapeutic target for the treatment of glioma. - Highlights: • LncRNA CCND2-AS1 was significantly upregulated in glioma cancer tissues and cell lines. • Overexpression CCND2-AS1 confers a poor prognosis in glioma patients. • Knockdown of CCND2-AS1 inhibited glioma cell proliferation and induced cell cycle arrest. • Overexpression CCND2-AS1 promotes cell growth in Normal human astrocyte (NHA). • LncRNA CCND2-AS1 regulates the activation of Wnt/β-catenin signaling in glioma cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Structural study of the effects of mutations in proteins to identify the molecular basis of the loss of local structural fluidity leading to the onset of autoimmune diseases

Protein-Protein Interactions (PPIs) are crucial in most of the biological processes and PPI dysfunctions are known to be associated with the onsets of various diseases. One of such diseases is the auto-immune disease. Auto-immune diseases are one among the less studied group of diseases with very high mortality rates. Thus, we tried to correlate the appearances of mutations with their probable biochemical basis of the molecular mechanisms leading to the onset of the disease phenotypes. We compared the effects of the Single Amino Acid Variants (SAVs) in the wild type and mutated proteins to identify any structural deformities that might lead to altered PPIs leading ultimately to disease onset. For this we used Relative Solvent Accessibility (RSA) as a spatial parameter to compare the structural perturbation in mutated and wild type proteins. We observed that the mutations were capable to increase intra-chain PPIs whereas inter-chain PPIs would remain mostly unaltered. This might lead to more intra-molecular friction causing a deleterious alteration of protein's normal function. A Lyapunov exponent analysis, using the altered RSA values due to polymorphic and disease causing mutations, revealed polymorphic mutations have a positive mean value for the Lyapunov exponent while disease causing mutations have a negative mean value. Thus, local spatial stochasticity has been lost due to disease causing mutations, indicating a loss of structural fluidity. The amino acid conversion plot also showed a clear tendency of altered surface patch residue conversion propensity than polymorphic conversions. So far, this is the first report that compares the effects of different kinds of mutations (disease and non-disease causing polymorphic mutations) in the onset of autoimmune diseases. - Highlights: • Protein-Protein Interaction. • Changes in Relative Solvent Accessibility (RSA). • Amino acid conversion matrix. • Polymorphic mutations. • Disease causing mutations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

DISCO interacting protein 2 determines direction of axon projection under the regulation of c-Jun N-terminal kinase in the Drosophila mushroom body

Precisely controlled axon guidance for complex neuronal wiring is essential for appropriate neuronal function. c-Jun N-terminal kinase (JNK) was found to play a role in axon guidance recently as well as in cell proliferation, protection and apoptosis. In spite of many genetic and molecular studies on these biological processes regulated by JNK, how JNK regulates axon guidance accurately has not been fully explained thus far. To address this question, we use the Drosophila mushroom body (MB) as a model since the α/β axons project in two distinct directions. Here we show that DISCO interacting protein 2 (DIP2) is required for the accurate direction of axonal guidance. DIP2 expression is under the regulation of Basket (Bsk), the Drosophila homologue of JNK. We additionally found that the Bsk/DIP2 pathway is independent from the AP-1 transcriptional factor complex pathway, which is directly activated by Bsk. In conclusion, our findings revealed DIP2 as a novel effector downstream of Bsk modulating the direction of axon projection. - Highlights: • DIP2 is required for accurate direction of axon guidance in Drosophila mushroom body. • DIP2 is a downstream of JNK in the axon guidance of Drosophila mushroom body neuron. • JNK/DIP2 pathway is independent from JNK/AP-1 transcriptional factor complex pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Tumor suppressive role of miR-1224-5p in keloid proliferation, apoptosis and invasion via the TGF-β1/Smad3 signaling pathway

The molecular mechanism of the pathogenesis of keloids is still not known and the clinical management of keloids remains challenging. MiRNA (microRNA) is a novel class of small regulatory RNAs that has emerged as key post-transcriptional regulators of gene expression. MiRNAs participate in diverse biological processes of various skin diseases and function as key regulators in the occurrence and development of tumors. The purpose of this study was to investigate the involvement of miRNAs in keloid pathogenesis. We performed miRNA microarray analysis to compare miRNA expression between keloid and normal skin samples. We found that 46 miRNAs were upregulated and 28 miRNAs were downregulated in keloid compared with normal skin samples. We focused on miR-1224-5p, which has been reported to function in cancers, although the expression and mechanism of miR-1224-5p in keloids remain to be explored. Overexpression of miR-1224-5p led to inhibition of keloid fibroblast proliferation, promotion of apoptosis and decrease of migration and invasion. Our results suggest that downregulation of miR-1224-5p may be one of the mechanisms involved in the occurrence and development of keloids.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Sequence conservation of protein binding segments in intrinsically disordered regions

Highlights: • Sequence conservation in protein-binding segments in IDRs is analyzed. • Functionally constraint residues in protein-binding segments in IDRs are conserved. • Evolutionary distance should be considered in the comparison of IDRs. • Cryptic binding regions may influence sequence conservation of IDRs. Intrinsically disordered proteins are proteins with intrinsically disordered regions (IDRs) that do not adopt a globular structure in their free state. IDRs have unique regions having protein-binding segments of which play pivotal roles in many biological processes. The binding sites in IDRs are heterogeneous in terms of their sequence conservation: some are conserved and others are not. We have been running a database of intrinsically disordered proteins, IDEAL, and collecting such binding segments, which are called protean segments (ProSs), within it. In this study, we compared the sequence conservation of ProSs, structural domains (SDs), and IDRs other than ProSs (non-ProSs) and found that i) functionally constrained residues in ProSs tend to be conserved, ii) the distribution of conservation scores of ProSs is similar to those of SDs but not non-ProSs, and iii) ProSs found in human proteins are mostly conserved only in vertebrates. These results indicate that the conservation patterns in ProSs principally follow the general rules found in SDs. However, we need to consider evolutionary distance when comparing IDR sequences because ProSs can readily emerge and disappear over the course of protein evolution. Moreover, many ProSs may remain to be identified, which may account for the heterogeneity of the sequence conservation of IDRs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Effects of connective tissue growth factor (CTGF/CCN2) on condylar chondrocyte proliferation, migration, maturation, differentiation and signalling pathway

Highlights: • It is the first discovery of CCN2 expression in the whole layers of condylar cartilage. • CCN2 promotes condylar chondrocyte migration, maturation and differentiation. • Blocking PI3K/Akt pathway impairs the stimulatory effect of CCN2 on the proliferation of condylar chondrocyte. CCN2, also known as connective tissue growth factor (CTGF), is a 38 kDa cysteine-rich extracellular matrix protein that regulates a sequence of cellular functions and participates in multiple complex biological processes, such as chondrogenesis and osteogenesis. In the present study, we provided the first evidence describing the physiological role of CCN2 in condylar chondrocyte proliferation, migration, maturation and differentiation. CCN2 was widely expressed throughout the whole layers of condylar cartilage and predominantly distributed in the proliferative zone. Recombinant CCN2 promoted the proliferation, migration, proteoglycan synthesis and differentiation capacity of isolated condylar chondrocytes. The stimulatory effect of CCN2 on chondrocyte proliferation was associated with the activation of phosphatidylinositol 3-kinase/Akt signalling pathway. The blocking of this pathway by its inhibitor LY294002 impaired the proliferative effect of CCN2 on chondrocytes. These results suggested a novel physiological role of CCN2 in the development of condylar cartilage.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Silencing LncRNA LOXL1-AS1 attenuates mesenchymal characteristics of glioblastoma via NF-κB pathway

Highlights: • LncRNA LOXL1-AS1 expression is increased in mesenchymal subtype of GBM. • Knocking down LOXL1-AS1 could suppresse GBM cell proliferation. • Silencing LncRNA LOXL1-AS1 Attenuates Mesenchymal Characteristics of Glioblastoma via reducing NF-κB transcription activity. The mesenchymal (MES) subtype of glioblastoma (GBM) suggested worse prognosis and a more malignant phenotype in comparison with their proneural (PN) counterpart. The plasticity between PN and MES transcriptome signatures provided clinical intervention with an manner. Few LncRNA, however, have been discovered to take part in the shift between subtypes. Here, we used transcriptomic data and experimental evidences to demonstrate that silencing LncRNA LOXL1-AS1 was a new regulator of NF-κB signaling pathway through repressing RELB directly, resulting in increased marker genes of PN subtype and decreased those of MES.GBM cell proliferation was functionally suppressed by LOXL1-AS1's knockdown expression,. Furthermore, RELB's rescue could reverse LOXL1-AS1's effects partially in GBM malignant behaviors. LOXL1-AS1 could clinically serve as a poor prognostic indicator for GBM patients. In conclusion, our results suggest that LOXL1-AS1 contributes to aggressive biological processes that are related with MES phenotype via NF-κB signaling, which expand our perceptions into the underlying mechanisms in LOXL1-AS1-based and subtype transition adapted medicine for GBM management.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MicroRNA-139-5p suppresses myosin heavy chain I and IIa expression via inhibition of the calcineurin/NFAT signaling pathway

Highlights: • MiR-139-5p was higher in mouse slow-twitch than in fast-twitch muscle. • MiR-139-5p overexpression downregulated the expression of MyHC I and MyHC IIa. • CaN/NFAT signaling was notably inhibited by miR-139-5p overexpression. • MiR-139-5p suppressed MyHC I and IIa expression via inhibiting CaN/NFAT signaling. MicroRNAs (miRNAs) are a class of small non-coding RNAs that are widely involved in a variety of biological processes. Different skeletal muscle fiber type composition exhibits characteristic differences in functional properties and energy metabolism of skeletal muscle. However, the molecular mechanism by which miRNAs control the different type of muscle fiber formation is still not fully understood. In the present study, we characterized the role of microRNA-139-5p (miR-139-5p) in the regulation of myosin heavy chain (MyHC) isoform expression and its underlying mechanisms. Here we found that the expression of miR-139-5p was significantly higher in mouse slow-twitch muscle than in fast-twitch muscle. Overexpression of miR-139-5p downregulated the expression of MyHC I and MyHC IIa, whereas inhibition of miR-139-5p upregulated them. We also found that the levels of calcineurin (CaN), NFATc1, MEF2C and MCIP1.4, which are the components of CaN/NFAT signaling pathway that has shown to positively regulate slow fiber-selective gene expression, were notably inhibited by miR-139-5p overexpression. Furthermore, treatment of phenylephrine (PE), a α1-adrenoceptor agonist, abolished the inhibitory effect of miR-139-5p on MyHC I and MyHC IIa expression. Together, our findings indicated that the role of miR-139-5p in regulating the MyHC isoforms, especially MyHC I and MyHC IIa, may be achieved through inhibiting CaN/NFAT signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RBM14 is indispensable for pluripotency maintenance and mesoderm development of mouse embryonic stem cells

Highlights: • RBM14 knockout mouse embryonic stem cells were successfully generated. • RBM14 depletion altered gene expression profiles in mouse embryonic stem cells. • RBM14 depletion impeded mesoderm development in vitro. • RBM14 depletion impeded mesoderm development in vivo. The pluripotency of embryonic stem cells (ESCs) is maintained by core pluripotency transcription factors, cofactors and several signaling pathways. RBM14 is a component of the para-speckle complex, which has been implicated in multiple important biological processes. The role of RBM14 in ESCs and lineage differentiation remains to be elucidated. In the present study, we provided evidence that RBM14 plays important roles in maintaining pluripotency and in the early differentiation of ESCs. RBM14 was demonstrated to be expressed in mouse embryonic stem cells (mESCs) and localized in the nucleus. RBM14 expression was depleted in mESCs using clustered regularly interspaced short palindromic repeats (CRISPR) technology. Our results also showed that RBM14 depletion altered the gene expression profiles of mESCs. In particular, pluripotency-associated genes and genes involved in the Wnt and TGF-β signaling pathways were downregulated in RBM14 knockout mESCs. Furthermore, RBM14 was found to be essential for mesoderm development in vitro and in vivo. The specific effects of RBM14 depletion were verified by conducting a rescue experiment. Our findings demonstrated that RBM14 not only plays an important role in maintaining the pluripotency of mESCs but is also indispensable for mesoderm development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Knockdown of Trnau1ap inhibits the proliferation and migration of NIH3T3, JEG-3 and Bewo cells via the PI3K/Akt signaling pathway

Highlights: • Knockdown of Trnau1ap attenuated cellular antioxidant activity. • Knockdown of Trnau1ap reduced cell migration and proliferation. • Knockdown of Trnau1ap blocked the PI3K/Akt signaling pathway. The tRNA selenocysteine 1 associated protein 1 (Trnau1ap, initially named SECp43) is involved in Selenocysteine (Sec) biosynthesis and incorporation into selenoproteins, which play a key role in biological processes, such as embryonic development. We previously reported that downregulation of Trnau1ap inhibited proliferation of cardiomyocyte-like H9c2 cells. However, the effects of Trnau1ap on cell proliferation and migration of embryonic development are not known, and the mechanisms remain elusive. Herein, lentiviral shRNA vectors were transfected in NIH3T3, JEG-3 and Bewo cells (embryonic, trophoblast and placental cells). We found that knockdown of Trnau1ap resulted in reduced expression levels of selenoproteins. The data of Cell Count Kit-8 (CCK-8) assay and wound scratch assay revealed the proliferation and migration rates were reduced in the Trnau1ap-shRNA groups. Furthermore, western blot analysis showed that the phosphorylation level of Akt in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was attenuated. These results indicate that Trnau1ap plays an important role in regulation of cell proliferation and migration through the PI3K/Akt signaling pathway, as well as being essential for embryonic development by regulating the expression of selenoproteins.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-193a inhibits osteogenic differentiation of bone marrow-derived stroma cell via targeting HMGB1

Highlights: • miR-193a inhibits osteogenic differentiation of hBMSC. • miR-193a attenuates activation of MAPK and Wnt signaling pathway. • miR-193a suppresses osteogenic differentiation partially via HMGB1. • HMGB1 greatly rescues miR-193a-inhibited activation of MAPK and Wnt signaling pathway. miR-193a has been shown to be involved in a variety of biological processes, including cell proliferation, differentiation, and apoptosis. However, little is known about how miR-193a regulates osteogenic differentiation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression

Highlights: • The prognostic value of m{sup 6}A methyltransferase and demethylase in lung cancer. • Differentially expressed FTO accounts for the aberrant m{sup 6}A modification in LUSC. • FTO acts as an oncogene in LUSC. • MZF1 mediates FTO regulation in LUSC. N{sup 6}-Methyladenosine (m{sup 6}A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m{sup 6}A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m{sup 6}A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m{sup 6}A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m{sup 6}A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m{sup 6}A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Synthesis and detoxification of nitric oxide in the plant beneficial rhizobacterium Bacillus amyloliquefaciens SQR9 and its effect on biofilm formation

Nitric oxide (NO) is an important gas signal that regulates many biological processes, and due to the high nitrogen recycling activity in the rhizosphere, NO is an important signaling molecule in this region. Thus, an understanding of the effect of NO on the rhizomicrobiome, especially on plant beneficial rhizobacteria, is important for the use of these bacteria in agriculture. In this study, the effect of exogenous NO on the beneficial rhizobacterium Bacillus amyloliquefaciens SQR9 was investigated. The results showed that low concentrations of NO increased the ability of the strain SQR9 to form biofilms, while high concentrations of NO inhibited the growth of this bacterium. The SQR9 gene yflM encodes nitric oxide synthase (NOS), which is used to synthesize NO, while the gene ykvO encodes a sepiapterin reductase that is used to synthesize tetrahydrobiopterin, the coenzyme of NOS. Isothermal titration calorimetry and high-performance liquid chromatography analyses demonstrated an interaction between YkvO and NADPH. SQR9 has two hmp genes, although only one was observed to be responsible for NO detoxification through oxidization. This study revealed the effect of NO on plant beneficial rhizobacterium and assessed the ability of this strain to adapt to exogenous NO, which will help to improve the application of this strain in agricultural production.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Circular RNA HIPK3 regulates human lens epithelial cells proliferation and apoptosis by targeting the miR-193a/CRYAA axis

Highlights: • CircRNA sequencing reveals 26 up-regulated and 75 down-regulated circRNAs in ARC. • CircHIPK3 is down-regulated in all three subtypes of ARC. • CircHIPK3 knockdown affects the cellular function in primary cultured HLECs. • CircHIPK3 exerts its role via modulation of circHIPK3/miR-193a/CRYAA axis in HLECs. Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated from back splicing. Accumulating evidence has demonstrated their vital regulation in several biological processes and ocular diseases. However, the role of circRNAs in age-related cataract (ARC), the leading cause of visual impairment worldwide, is still unknown. CircRNA sequencing reveals that 101 circRNAs are differentially expressed between the capsules of transparent and ARC lenses, including 75 down-regulated circRNAs and 26 up-regulated circRNAs transcripts. Eight of 10 differentially expressed circRNAs are further verified by quantitative RT-PCRs. One highly conserved circRNA, circHIPK3, is significantly down-regulated in all cortical, nuclear and posterior subcapsular subtypes of ARC. The silencing of circHIPK3, but not HIPK3 mRNA, significantly accelerates apoptosis development upon oxidative stress and decreases cell viability and proliferation in primary cultured human lens epithelial cells (HLECs). The expression of α-SMA and vimentin was downregulated, while the expression of E-cadherin and ZO-1was upregulated, suggesting the repression of epithelial-mesenchymal transition after circHIPK3 knockdown. CircHIPK3 silencing increases miR-193a expression. miR-193a regulates CRYAA expression by targeting the binding site within the 3′UTR. Moreover, miR-193a decreases the viability and proliferation, and increases the apoptosis of HLECs upon oxidative stress. This study suggests that circRNAs are the potential regulators in cataractogenesis. CircHIPK3 regulates HLECs function through miR-193a-mediated CRYAA expression. This finding would provide a novel insight into the pathogenesis of ARC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

FoxO1 expression in osteoblasts modulates bone formation through resistance to oxidative stress in mice

Accumulation of reactive oxygen species (ROS) induced by oxidative stress (OS) affects cell survival, cell function and even results in cell death. As a major transcription factor of forkhead O (FoxOs) family, FoxO1 orchestrates multiple osteoblastic biological processes, thus regulating osteoblast physiology and bone metabolism. However, the outcome of osteoblast behaviors varies under different physiological and pathological conditions. Also, the underlying impact of FoxO1 on oxidative stress and further on bone metabolism still remains unclear. In this study, using osteoblast-specific FoxO1 knockout (FoxO1{sub OB}{sup -/-}) mice, we investigated the potential roles of FoxO1 on bone formation and osteoblast bioactivity under physiological condition. We show herein that FoxO1-knockout decreased bone volume and bone formation rate in FoxO1{sub OB}{sup -/-} mice, which might be related to the decreased osteoblasts number. We also found that FoxO1-knockout increased apoptosis-related caspase-3 activity of osteoblasts, and inhibited the expression of osteogenic phenotypic markers (i.e. Runx2, Osx, ALP and OPN), leading to reduced osteoblasts differentiation. The alterations of bone formation and osteoblasts bioactivity were further testified to be linked to the elevated intracellular oxidative stress levels in FoxO1-deficient osteoblasts. Besides, administration of the antioxidant N-acetyl-l-cysteine (NAC) normalized the increased ROS levels in FoxO1-deficient osteoblasts, restoring the decreased osteoblasts differentiation, suppressing apoptosis-related caspase-3 activity, and promoting the expression of osteogenic markers in FoxO1-deficient osteoblasts. These results together illustrated that as a major regulator in redox homeostasis and osteoblast physiology, FoxO1 provides a favorable intracellular environment for osteoblast functions by defensing against the adverse effects of oxidative stress.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Differential inhibition of mucin-type O-glycosylation (MTOG) induced by peracetyl N-thioglycolyl-d-galactosamine (Ac5GalNTGc) in myeloid cells

Highlights: • Each cell type expresses specific set of glycosyl transferases that result in unique pattern of mucin-type O-glycosylation. • MTOG of CD antigens is regulated depending on the specific cell type, developmental stage, and resting or activated state. • Metabolic incorporation of N-thioglycolyl-d-galactosamine results in cell-type dependent differential inhibition of MTOG. • Myeloid cells metabolize Ac{sub 5}GalNTGc with varying efficiency resulting in differential inhibition of MTOG on CD43. Investigations on the structure and functional roles of glycosylation – an intricate, complex, and dynamic post translational modification on proteins – in biological processes has been a challenging task. Glycan modifications vary depending on the specific cell type, its developmental stage, and resting or activated state. In the present study, we aim to understand the differences between the mucin-type O-glycosylation (MTOG) of two functionally divergent human cell lines, K562 (chronic myeloid leukemia) and U937 (histiocytic lymphoma), having myeloid origins. MTOG is initiated by the addition of N-acetyl-α-d-galactosamine (GalNAc) to Ser/Thr of glycoproteins. We exploited the metabolic glycan engineering (MGE) strategy using the peracetyl N-thioglycolyl-d-galactosamine (Ac{sub 5}GalNTGc), a synthetic GalNAc analogue, to engineer the glycoconjugates. Ac{sub 5}GalNTGc was metabolized and incorporated as N-thioglycolyl-d-galactosamine (GalNTGc) in cell surface glycoproteins in both the cell lines with varying degrees of efficiency. Notably, metabolic incorporation of GalNTGc resulted in differential inhibition of MTOG. It was observed that endogenous glycosylation machinery of K562 is relatively more stringent for selecting GalNTGc whereas U937 is flexible towards this selection. Additionally, we studied how the glycan modifications vary on a given CD antigen in these cell lines. Particularly, MTOG on CD43 was differentially inhibited in K562 and U937 as revealed by glycan-dependent and glycan-independent antibodies. It was observed that the effect of MGE on CD43 was similar to global effects on both cell lines. Consequences of MGE using GalNAc analogues depend on the expression and activity of various glycosyl transferases which determine global glycosylation on cell surface as well as on specific glycoproteins.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Global identification of circular RNAs in chronic myeloid leukemia reveals hsa{sub c}irc{sub 0}080145 regulates cell proliferation by sponging miR-29b

Highlights: • A large number of circRNAs aberrantly expressed in chronic myeloid leukemia. • Top 20 aberrantly expressed interacted with leukemia-associated miRNAs. • hsa{sub c}irc{sub 0}080145 knockdown significantly suppressed CML cell proliferation. • hsa{sub c}irc{sub 0}080145 acts as an miR-29b sponge in CML. Circular RNAs (circRNAs) are a class of non-coding RNAs that participate in various biological processes and disease pathogenesis. However, the role of circRNAs in chronic myeloid leukemia (CML) remains largely unknown. In this study, high-throughput sequencing was performed to explore the expression profile of circRNAs in CML patients for the first time, and a large number of differentially expressed circRNAs were identified. In addition, we constructed potential circRNA-miRNA interaction networks in CML, including a detailed hsa{sub c}irc{sub 0}080145-mediated competing endogenous RNA (ceRNA) regulatory network. Furthermore, functional experiments demonstrated that hsa{sub c}irc{sub 0}080145 knockdown significantly suppressed CML cell proliferation and hsa{sub c}irc{sub 0}080145 regulated CML cell proliferation by acting as an miR-29b sponge.

60 APPLIED LIFE SCIENCES↗