Displaying publications 521 - 540 of 1901 in total

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  1. Navien TN, Thevendran R, Hamdani HY, Tang TH, Citartan M
    Biochimie, 2020 Oct 18;180:54-67.
    PMID: 33086095 DOI: 10.1016/j.biochi.2020.10.005
    Aptamers are single-stranded DNA or RNA oligonucleotides generated by SELEX that exhibit binding affinity and specificity against a wide variety of target molecules. Compared to RNA aptamers, DNA aptamers are much more stable and therefore are widely adopted in a number of applications especially in diagnostics. The tediousness and rigor associated with certain steps of the SELEX intensify the efforts to adopt in silico molecular docking approaches together with in vitro SELEX procedures in developing DNA aptamers. Inspired by these endeavors, we carry out an overview of the in silico molecular docking approaches in DNA aptamer generation, by detailing the stepwise procedures as well as shedding some light on the various softwares used. The in silico maturation strategy and the limitations of the in silico approaches are also underscored.
    Matched MeSH terms: RNA
  2. Sato H, Torii H, Une Y, Ooi HK
    J Parasitol, 2007 Dec;93(6):1476-86.
    PMID: 18314696 DOI: 10.1645/GE-1106.1
    Strongyloides callosciureus n. sp. (Nematoda: Rhabditoidea), from Asian sciurids, is described based on morphology, morphometry, and the small and large subunit (SSU/LSU) ribosomal RNA gene (rDNA) sequences. This new species was collected from Pallas's squirrels (Callosciurus erythraeus) in the central part of mainland Japan (Honshu), which were originally introduced from Taiwan some decades ago, and plantain squirrels (Callosciurus notatus) imported from Malaysia as personal pets. For comparison, Strongyloides robustus Chandler, 1942 was collected from American red squirrels (Tamiasciurus hudsonicus) and southern flying squirrels (Glaucomys volans) imported from the United States as personal pets. The parasitic females found in North American and Asian sciurids shared some key morphological features such as the ovary running spirally around the gut, and the shapes of the stoma in the apical view and the tail. However, morphometric features of parasitic females in North American and Asian sciurids differed significantly from each other; the former was larger than the latter, and the relative position of the vulva to the whole body length from the mouth was different. The SSU/LSU rDNA sequences supported the division of sciurid Strongyloides isolates by geographical distribution of the host and morphological features, leading us to propose the erection of new species.
    Matched MeSH terms: RNA, Ribosomal, 18S/genetics; RNA, Ribosomal, 28S/genetics
  3. Le Van Thien, Ngo Thi Tuong Chau, Pham Thi Ngoc Lan, Hiroyuki Futamata
    Sains Malaysiana, 2018;47:1051-1060.
    Pulp and paper mill sludge (PPMS) was found to be poorly colonised with thermophilic microorganisms. However,
    evidence to support the need for inoculation to facilitate PPMS composting has only been demonstrated in one instance.
    In this study, we aimed to: screen and identify PPMS digesting thermophilic bacterial strains; investigate effects of the
    mixture of selected thermophilic bacterial strains on PPMS digestion; and utilize this mixture as start inoculum in PPMS
    composting and assess the quality of compost product. The results showed that eleven thermophilic bacterial strains were
    isolated from Bai Bang PPMS by the enrichment culture method. Among these, three strains which reflected high growth
    rates on the plates of Minimal Media Agar supplemented with Bai Bang PPMS and showed hydrolytic and ligninolytic
    activities on the agar plates containing appropriate inductive substrates were selected. Based on the morphological,
    biochemical characteristics and 16S rRNA gene sequencing, they were identified as Bacillus subtilis. The inoculation
    with the mixture of selected strains enhanced remarkably Bai Bang PPMS digestion. The dry weight decrease, volatile
    suspended solids removal, dehydrogenase and protease activities in the inoculated sludge were 2.1-, 1.5-, 1.3- and 1.2-
    fold higher, respectively, compared to the non-inoculated sludge. The assessment of compost quality based on stability
    using the alkaline trap method and maturity using the germination and root elongation test showed that the inoculated
    compost was stable and mature while the non-inoculated compost was unstable and immature. These thermophilic
    bacterial strains therefore have great potential for Bai Bang PPMS composting.
    Matched MeSH terms: RNA, Ribosomal, 16S
  4. Shafiq N, Kumar R, Zahid M, Tufail RF
    Materials (Basel), 2019 Jul 17;12(14).
    PMID: 31319615 DOI: 10.3390/ma12142291
    This paper discussed the effects of modified metakaolin (MK) with nano-silica (NS) on the mechanical properties and durability of concrete. In the first phase, trial mixes of concrete were prepared for achieving the desired value of the 28 days compressive strength, and the charge passed in rapid chloride permeability test (RCPT). In the second phase, statistical analysis was performed on the experimental results using the response surface method (RSM). The RSM was applied for optimizing the mix proportions for the required performance by exploiting the relationship between the mix characteristics and the corresponding test results. A blend of 10% MK + 1% NS as part of cement replacement exhibited the highest mechanical properties and durability characteristics of concrete; concrete mix showed that the 28-days compressive strength (CS) was 103 MPa, which was 15% greater than the CS of the control mix without MK or NS. The same mix showed more than 40% higher flexural and split-tensile strength than the control mix; also it resulted in a reduction of 73% in the rapid chloride permeability value. ANOVA technique was used for optimizing the nano-silica and metakaolin content for achieving maximum compressive strength and minimum RCPT value. Statistical analysis using ANOVA technique showed that the maximum compressive strength and lowest RCPT value could be achieved with a blend of 10% MK and 1.55% NS.
    Matched MeSH terms: RNA-Binding Proteins
  5. Lim FS, Khoo JJ, Tan KK, Zainal N, Loong SK, Khor CS, et al.
    Ticks Tick Borne Dis, 2020 03;11(2):101352.
    PMID: 31866439 DOI: 10.1016/j.ttbdis.2019.101352
    Ticks are hematophagous vectors of arthropod-borne disease agents globally. In Malaysia, despite seroprevalence studies indicating the presence of tick-borne diseases among the indigenous people, the etiological agents of these diseases are still unclear. These indigenous people, also known as the Orang Asli, still live in forested areas with frequent contact with wildlife. Wild boar are ubiquitously found in the forested areas where the Orang Asli communities are located and are commonly hunted as a food supplement. In this study, we aim to determine the tick species parasitizing wild boar from an Orang Asli community, and explore the tick-associated bacterial communities using 16 s rRNA amplicon sequencing on the Ion Torrent PGM™ platform. A total of 72 ticks were collected from three wild boar and were morphologically identified as Haemaphysalis hystricis (n = 32), Dermacentor compactus (n = 15), Amblyomma testudinarium (n = 13), Dermacentor steini (n = 10) and Dermacentor atrosignatus (n = 2). Across all tick samples, 910 bacterial taxa were identified. Although the bacterial communities were not significantly distinct between tick species in beta-diversity analyses, Coxiella, Rickettsia and Francisella were detected at high relative abundance in H. hystricis, D. compactus and D. steini respectively. Many other bacterial genera, including those that have been described in many different tick species, were also identified, including Pseudomonas, Acinetobacter, Staphylococcus and Corynebacterium. Beta-diversity analyses also showed that the bacterial communities were separated based on the animal host from which the ticks were collected from, suggesting that the bacterial communities here may be influenced by the animal skin microflora, host blood or the environment. PCR screening confirmed the presence of Rickettsia sp. related to spotted fever group Rickettsia in some of the ticks. This study provides baseline knowledge of the microbiome of H. hystricis, D. atrosignatus, D. compactus, D. steini and A. testudinarium parasitizing wild boar in this region. The information gained in this study provides the basis to target our efforts in H. hystricis, D. compactus and D. steini for the future investigation of vector competence and the zoonotic potential for the Coxiella, Rickettsia and Francisella detected here, as well as their implications for the risks of tick-borne diseases among the Orang Asli communities.
    Matched MeSH terms: RNA, Bacterial/analysis; RNA, Ribosomal, 16S/analysis
  6. Guan J, He Z, Qin M, Deng X, Chen J, Duan S, et al.
    BMC Infect Dis, 2021 Feb 10;21(1):166.
    PMID: 33568111 DOI: 10.1186/s12879-021-05823-3
    BACKGROUND: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported.

    METHODS: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed.

    RESULTS: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q → H) and 670th (E390: N → S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China.

    CONCLUSIONS: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.

    Matched MeSH terms: RNA, Viral/metabolism; RNA, Viral/chemistry; Sequence Analysis, RNA
  7. Ahmad Nazri MUI, Mahmud MH, Saidi B, Mat Isa MN, Ehsak Z, Ross O, et al.
    Heliyon, 2021 Feb;7(2):e06307.
    PMID: 33681499 DOI: 10.1016/j.heliyon.2021.e06307
    The polychaete Diopatra claparedii Grube, 1878 is among those organisms successfully carrying out full body regeneration, including the whole nervous system. Thus, D. claparedii potentially can be regarded for the nervous system regeneration (NSR) study. However, data on the property of its nervous system and the NSR profile are still lacking. In this study, we investigated the morphology of D. claparedii anterior nervous system (ANS) and examined the cellular and molecular profiles on its early anterior NSR. The nervous system of D. claparedii consists of a symmetry brain with nerves branching off, circumpharyngeal connectives that connect the brain and nerve cord as well as obvious segmental ganglia. Moreover, we identified changes in the cellular condition of the ganglionic cells in the regenerating tissue, such as the accumulation of lysosomes and lipofuscins, elongated mitochondria and multiple nucleoli. Furthermore, mRNA of tissues at two regenerating stages, as well as intact tissue (non-regenerating), were sequenced with Illumina sequencer. We identified from these tissues 37,248 sequences, 18 differential expressed proteins of which upregulated were involved in NSR with noelin-like isoform X2 turned up to be the highest being expressed. Our results highlight the cellular and molecular changes during early phase of NSR, thus providing essential insights on regeneration within Annelida and understanding the neurodegenerative diseases.
    Matched MeSH terms: RNA, Messenger
  8. Jahari PNS, Mohd Azman S, Munian K, Ahmad Ruzman NH, Shamsir MS, Richter SR, et al.
    Mitochondrial DNA B Resour, 2021 Feb 11;6(2):502-504.
    PMID: 33628904 DOI: 10.1080/23802359.2021.1872433
    Two mitogenomes of long-tailed giant rat, Leopoldamys sabanus (Thomas, 1887), which belongs to the family Muridae were sequenced and assembled in this study. Both mitogenomes have a length of 15,973 bp and encode 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes and one control region. The circular molecule of L. sabanus has a typical vertebrate gene arrangement. Phylogenetic and BLASTn analysis using 10 Leopoldamys species mitogenomes revealed sequence variation occurred within species from different time zones. Along with the taxonomic issues, this suggests a landscape change might influence genetic connectivity.
    Matched MeSH terms: RNA, Transfer
  9. Huertas-Rosales Ó, Romero M, Chan KG, Hong KW, Cámara M, Heeb S, et al.
    Front Mol Biosci, 2021;8:624061.
    PMID: 33693029 DOI: 10.3389/fmolb.2021.624061
    Post-transcriptional regulation is an important step in the control of bacterial gene expression in response to environmental and cellular signals. Pseudomonas putida KT2440 harbors three known members of the CsrA/RsmA family of post-transcriptional regulators: RsmA, RsmE and RsmI. We have carried out a global analysis to identify RNA sequences bound in vivo by each of these proteins. Affinity purification and sequencing of RNA molecules associated with Rsm proteins were used to discover direct binding targets, corresponding to 437 unique RNA molecules, 75 of them being common to the three proteins. Relevant targets include genes encoding proteins involved in signal transduction and regulation, metabolism, transport and secretion, stress responses, and the turnover of the intracellular second messenger c-di-GMP. To our knowledge, this is the first combined global analysis in a bacterium harboring three Rsm homologs. It offers a broad overview of the network of processes subjected to this type of regulation and opens the way to define what are the sequence and structure determinants that define common or differential recognition of specific RNA molecules by these proteins.
    Matched MeSH terms: RNA
  10. Tan PPS, Hall D, Chilian WM, Chia YC, Mohd Zain S, Lim HM, et al.
    Am J Physiol Heart Circ Physiol, 2021 04 01;320(4):H1486-H1497.
    PMID: 33577433 DOI: 10.1152/ajpheart.00888.2020
    MicroRNAs (miRNAs) are small regulatory molecules that are involved in posttranscriptional modifications. These noncoding RNAs are usually ferried by extracellular carriers such as exosomes or other protein and lipid carriers inside a range of body fluids including plasma and urine. Due to their ability to withstand harsh external conditions, exosomal miRNAs possess enormous potential as noninvasive disease biomarkers for, notably hypertension, whereby exosomal miRNAs have been implicated in its pathophysiological processes. More importantly, alterations in the microenvironment as a result of disease progression can induce active and selective loading of miRNAs into exosomes. In this paper, we first review the mechanisms of miRNA loading into exosomes, followed by the roles of exosomal miRNAs in the development of hypertension, and the potentials of exosomal miRNAs as biomarkers in comparison with other free circulating miRNAs. Finally, challenges and future research surrounding exosomal miRNAs will also be discussed. This review will aid in the understanding of noninvasive biomarkers for the early diagnosis of hypertension and for probing therapeutic efficacy.
    Matched MeSH terms: RNA, Untranslated
  11. Nor Muhammad NA, Ramlee IA, Mohd Nor D, Satyavenathan MV, Rahmat NL, Awang A, et al.
    Data Brief, 2021 Feb;34:106638.
    PMID: 33365368 DOI: 10.1016/j.dib.2020.106638
    Cocoa bean (Theobroma cacao L.) is part of the global cocoa and chocolate industry valued at 44 billion US dollars in 2019. Cocoa pod borer (CPB), Conopomorpha cramerella is a major pest of cocoa in Malaysia and Indonesia that is responsible for the decline for cocoa production. They have been detected since 1980s. Unfortunately, current control strategies are inefficient for CPB management. Although biotechnological alternatives, including RNA interference (RNAi), have been proposed in recent years to control insect pests, characterizing the genetics of the target pest is essential for successful application of these emerging technologies. We generated a comprehensive RNA-seq dataset (135,915,430 clean reads) for larva and adult stages of CPB by using the Illumina HiseqTM 4000 system to increase the understanding of CPB in relation to molecular features. The CPB transcriptome was assembled de novo and annotated. The final assembled produced 249,280 unigenes, of which 75,929 unigenes annotated against NCBI NR database and were distributed among 156 KEGG pathways. The raw data were uploaded to SRA database and the BioProject ID is PRJNA553611. The transcriptomic dataset we present are the first reports of transcriptome information in CPB that is valuable for further exploration and understanding of CPB molecular pathways.
    Matched MeSH terms: RNA Interference
  12. Yang MJ, Liu JH, Wan XS, Zhang QL, Fu DY, Wang XB, et al.
    Mitochondrial DNA B Resour, 2020 Oct 27;5(3):3638-3639.
    PMID: 33367040 DOI: 10.1080/23802359.2020.1831984
    The black-winged fly, Felderimyia fuscipennis (Diptera: Tephritidae), is an insect pest of bamboo shoot, mainly distributed in Thailand, Malaysia and Yunnan Province and Guangxi Autonomous Region, China. The complete sequence of the mitogenome of F. fuscipennis has been determined in this study. The whole mitogenome sequence is 16,536 bp in length, which totally contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a non-coding region (putative control region, CR). The phylogeny indicates that F. fuscipennis of subfamily Trypetinae was monophyletic and clearly separated from both Dacinae and Tephritinae with high bootstrap value supported.
    Matched MeSH terms: RNA, Transfer
  13. Jahari PNS, Mohd Azman S, Munian K, Zakaria NA, Omar MSS, Richter SR, et al.
    Mitochondrial DNA B Resour, 2021 Jan 12;6(1):53-55.
    PMID: 33521264 DOI: 10.1080/23802359.2020.1846472
    We assembled the complete mitogenome of Cynopterus sphinx (Vahl, 1797) of the family Pteropodidae originating from Malaysia. The total mitogenome size was 16,710bp which consists of 37 genes (13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one control region). A phylogenetic and BLASTn result showed the mitogenome sequence in this study varies by nearly 7% (93.48% similarity) from the same species in Cambodia. The next closest match of BLASTn was at 92% similarity to the C. brachyotis. This suggests the species-complex in Cynopterus sp. has given rise to the genetic variability.
    Matched MeSH terms: RNA, Transfer
  14. Teoh SL, Lim YH, Lai NM, Lee SWH
    Front Microbiol, 2020;11:1857.
    PMID: 32849448 DOI: 10.3389/fmicb.2020.01857
    The outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China in December 2019 has now become a pandemic with no approved therapeutic agent. At the moment, the genomic structure, characteristics, and pathogenic mechanisms of SARS-CoV-2 have been reported. Based upon this information, several drugs including the directly acting antivirals have been proposed to treat people with coronavirus disease 2019 (COVID-19). This rapid review aims to describe the directly acting antivirals that have been examined for use in the management of COVID-19. Searches were conducted in three electronic databases, supplemented with a search on arXiv, bioRxiv, medRxiv, ChinaXiv, ClinicalTrials.gov, and Chinese Clinical Trial Registry for studies examining the use of antivirals in COVID-19 to identify for case reports, case series, observational studies, and randomized controlled studies describing the use of antivirals in COVID-19. Data were extracted independently and presented narratively. A total of 98 studies were included, comprising of 38 published studies and 60 registered clinical trials. These drugs include the broad spectrum antivirals such as umifenovir, protease inhibitors such as lopinavir/ritonavir as well as the RNA-dependent RNA polymerase inhibitors, remdesivir, and favipiravir. Other drugs that have been used include the nucleosidase inhibitors and polymerase acidic endonuclease inhibitors which are currently approved for prevention of influenza infections. While some of the drugs appear promising in small case series and reports, more clinical trials currently in progress are required to provide higher quality evidence.
    Matched MeSH terms: RNA Replicase
  15. Xie Z, Tan H, Lin F, Guan M, Waiho K, Fang S, et al.
    Mitochondrial DNA B Resour, 2018 Mar 27;3(1):397-398.
    PMID: 33474181 DOI: 10.1080/23802359.2018.1456374
    The complete mitochondrial genome sequence of Atergatis integerrimus from China has been amplified and sequenced in this study. The mitogenome assembly was found to be 15,924 bp in length with base composition of A (32.88%), G (10.58%), C (20.87%), T (35.66%), A + T (68.54%), and G + C (31.46%). It contained 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a control region. The phylogenetic position was constructed and the A. integerrimus was closely clustered with Pseudocarcinus gigas and Leptodius sanguineus. The complete mitochondrial genome sequence would be useful for further understanding the evolution of A. integerrimus.
    Matched MeSH terms: RNA, Transfer
  16. Lin F, Xie Z, Fazhan H, Baylon JC, Yang X, Tan H, et al.
    Mitochondrial DNA B Resour, 2018 Feb 23;3(1):263-264.
    PMID: 33474136 DOI: 10.1080/23802359.2018.1443043
    The complete mitochondrial genome plays an important role in the research on phylogenetic relationship. Here, we reported the first complete mitochondrial genome sequence of Varuna yui Hwang & Takeda, 1986 (Varunidae). The complete mtDNA (15,915 bp in length) consisted of 13 protein-coding genes, 22 tRNAs, two rRNA genes, and a control region. The gene arrangement was identical to those observed in the Varunidae species. The phylogenetic analysis suggested that V. yui had close relationship with other Varunidae species (Helicetient sinensis, Eriocher sinesis, etc.). The newly described genome may facilitate further comparative mitogenomic analysis within Varunidae species.
    Matched MeSH terms: RNA, Transfer
  17. Matthew P, Manjaji-Matsumoto BM, Rodrigues KF
    Mitochondrial DNA B Resour, 2018 Oct 12;3(2):943-944.
    PMID: 33474374 DOI: 10.1080/23802359.2018.1473725
    We report here the complete mitochondrial (mt) genomes of six individuals of Cheilinus undulatus (Napoleon Wrasse), an endangered marine fish species. The six mt DNA sequences had an average size of 17,000 kb and encoded 22 tRNA, two sRNA, 13 highly conserved protein coding genes and a control region. The polymorphic variation (control region) in these six individuals suggests their potential use as a specific marker for phylogeographic conservation. Moreover, the sequence polymorphism within the control region (D-loop) suggests that this locus can be applied for phylogenetic studies.
    Matched MeSH terms: RNA, Transfer
  18. Okuyama H, Tingek S, Takahashi JI
    Mitochondrial DNA B Resour, 2017 Jul 31;2(2):475-476.
    PMID: 33473869 DOI: 10.1080/23802359.2017.1361344
    The complete mitochondrial genome of the cavity-nesting honeybee Apis cerana from Sabah on Borneo Island was analyzed using next-generation sequencing. The mitochondrial genome of A. cerana was a circular molecule of 15,884 bp and was similar to that of the other cavity-nesting honeybee species. The average AT content in the A. cerana mitochondrial genome was 84.4%. It was predicted to contain 13 protein-coding, 22 tRNA, and two rRNA genes, along with one A + T-rich control region.
    Matched MeSH terms: RNA, Transfer
  19. Chan LL, Mak JW, Low YT, Koh TT, Ithoi I, Mohamed SM
    Acta Trop, 2011 Jan;117(1):23-30.
    PMID: 20858455 DOI: 10.1016/j.actatropica.2010.09.004
    During a study on the quality of the indoor environment, Acanthamoeba spp. were detected in 20 out of 87 dust samples collected from air-conditioners installed in a four-story campus building located in Kuala Lumpur, Malaysia. Twenty-one cloned Acanthamoeba isolates designated as IMU1 to IMU21 were established from the positive primary cultures. Five species were identified from the 16 isolates according to the morphological criteria of Pussard and Pons; i.e. A. castellanii, A. culbertsoni, A. griffini, A. hatchetti and A. polyphaga. Species identities for the remaining five isolates (IMU4, IMU5, IMU15, IMU20 and IMU21), however, could not be determined morphologically. At genotypic characterization, these isolates were placed into T3 (IMU14); T5 (IMU16 and IMU17) and T4 (all the remaining isolates). To predict the potential pathogenicity of these Acanthamoeba isolates, thermo- and osmotolerance tests were employed; many isolates were predicted as potential human pathogens based on the outcome of these tests. This is the first time potentially pathogenic Acanthamoeba have been isolated from air-conditioners in Malaysia.
    Matched MeSH terms: RNA, Ribosomal, 18S/genetics; RNA, Protozoan/genetics
  20. Che Mat MF, Abdul Murad NA, Ibrahim K, Mohd Mokhtar N, Wan Ngah WZ, Harun R, et al.
    Int J Oncol, 2016 Dec;49(6):2359-2366.
    PMID: 27840905 DOI: 10.3892/ijo.2016.3755
    Glioblastoma multiforme (GBM) is an aggressive brain tumor and most patients have poor prognosis. Despite many advances in research, there has been no significant improvement in the patient survival rate. New molecular therapies are being studied and RNA interference (RNAi) therapy is one of the promising approaches to improve prognosis and increase survival in patients with GBM. We performed a meta‑analysis of five different microarray datasets and identified 460 significantly upregulated genes in GBM. Loss‑of‑function screening of these upregulated genes using LN18 cells was performed to identify the significant target genes for glioma. Further investigations were performed using siRNA in LN18 cells and various functional assays were carried out on the selected candidate gene to understand further its role in GBM. We identified PROS1 as a candidate gene for GBM from the meta‑analysis and RNAi screening. Knockdown of PROS1 in LN18 cells significantly induced apoptosis compared to siPROS1‑untreated cells (p<0.05). Migration in cells treated with siPROS1 was reduced significantly (p<0.05) and this was confirmed with wound-healing assay. PROS1 knockdown showed substantial reduction in cell invasion up to 82% (p<0.01). In addition, inhibition of PROS1 leads to decrease in cellular proliferation by 18%. Knockdown of PROS1 in LN18 cells caused activation of both of the extrinsic and intrinsic apoptotic pathways. It caused major upregulation of FasL which is important for death receptor signaling activation and also downregulation of GAS6 and other members of TAM family of receptors. PROS1 may play an important role in the development of GBM through cellular proliferation, migration and invasion as well as apoptosis. Targeting PROS1 in GBM could be a novel therapeutic strategy in GBM treatment.
    Matched MeSH terms: RNA Interference; RNA, Small Interfering/genetics; RNA, Small Interfering/therapeutic use
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