Displaying publications 1 - 20 of 267 in total

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  1. Jegathesan Y, Stephen PP, Sati ISEE, Narayanan P, Monif M, Kamarudin MNA
    Biomed Pharmacother, 2024 Mar;172:116277.
    PMID: 38377734 DOI: 10.1016/j.biopha.2024.116277
    Notorious for its high mortality rate, the current standard treatment for high-grade gliomas remains a challenge. This is largely due to the complex heterogeneity of the tumour coupled with dysregulated molecular mechanisms leading to the development of drug resistance. In recent years, microRNAs (miRNAs) have been considered to provide important information about the pathogenesis and prognostication of gliomas. miRNAs have been shown to play a specific role in promoting oncogenesis and regulating resistance to anti-glioma therapeutic agents through diverse cellular mechanisms. These include regulation of apoptosis, alterations in drug efflux pathways, enhanced activation of oncogenic signalling pathways, Epithelial-Mesenchymal Transition-like process (EMT-like) and a few others. With this knowledge, upregulation or inhibition of selected miRNAs can be used to directly affect drug resistance in glioma cells. Moreover, the clinical use of miRNAs in glioma management is becoming increasingly valuable. This comprehensive review delves into the role of miRNAs in drug resistance in high-grade gliomas and underscores their clinical significance. Our analysis has identified a distinct cluster of oncogenic miRNAs (miR-9, miR-21, miR-26a, miR-125b, and miR-221/222) and tumour suppressive miRNAs (miR-29, miR-23, miR-34a-5p, miR 181b-5p, miR-16-5p, and miR-20a) that consistently emerge as key players in regulating drug resistance across various studies. These miRNAs have demonstrated significant clinical relevance in the context of resistance to anti-glioma therapies. Additionally, the clinical significance of miRNA analysis is emphasised, including their potential to serve as clinical biomarkers for diagnosing, staging, evaluating prognosis, and assessing treatment response in gliomas.
    Matched MeSH terms: Up-Regulation
  2. Haris K, Ismail S, Idris Z, Abdullah JM, Yusoff AA
    Asian Pac J Cancer Prev, 2014;15(11):4499-505.
    PMID: 24969876
    Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
    Matched MeSH terms: Up-Regulation/drug effects; Up-Regulation/genetics
  3. Sugiatno E, Samsudin AR, Sosroseno W
    J Appl Biomater Biomech, 2009 Jan-Apr;7(1):29-33.
    PMID: 20740436
    The aim of this study was to test the hypothesis that the proliferation of hydroxyapatite (HA)-induced human osteoblast cell line (HOS cells) may be up-regulated by exogenous nitric oxide (NO).
    Matched MeSH terms: Up-Regulation
  4. Liew KJ, Bruce NC, Sani RK, Chong CS, Yaakop AS, Shamsir MS, et al.
    Microorganisms, 2020 Jun 29;8(7).
    PMID: 32610703 DOI: 10.3390/microorganisms8070976
    The majority of the members in order Rhodothermales are underexplored prokaryotic extremophiles. Roseithermus, a new genus within Rhodothermales, was first described in 2019. Roseithermus sacchariphilus is the only species in this genus. The current report aims to evaluate the transcriptomic responses of R. sacchariphilus strain RA when cultivated on beechwood xylan. Strain RA doubled its growth in Marine Broth (MB) containing xylan compared to Marine Broth (MB) alone. Strain RA harbors 54 potential glycosyl hydrolases (GHs) that are affiliated with 30 families, including cellulases (families GH 3, 5, 9, and 44) and hemicellulases (GH 2, 10, 16, 29, 31,43, 51, 53, 67, 78, 92, 106, 113, 130, and 154). The majority of these GHs were upregulated when the cells were grown in MB containing xylan medium and enzymatic activities for xylanase, endoglucanase, β-xylosidase, and β-glucosidase were elevated. Interestingly, with the introduction of xylan, five out of six cellulolytic genes were upregulated. Furthermore, approximately 1122 genes equivalent to one-third of the total genes for strain RA were upregulated. These upregulated genes were mostly involved in transportation, chemotaxis, and membrane components synthesis.
    Matched MeSH terms: Up-Regulation
  5. Shetty SS, Sharma M, Fonseca FP, Jayaram P, Tanwar AS, Kabekkodu SP, et al.
    Jpn Dent Sci Rev, 2020 Nov;56(1):97-108.
    PMID: 32874377 DOI: 10.1016/j.jdsr.2020.07.002
    Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.
    Matched MeSH terms: Up-Regulation
  6. Phei-Lian, Wang, Edmund Sim, Ui Hang
    MyJurnal
    Increasing evidence of the association between ribosomal protein (RP) genes with nasopharyngeal carcinoma (NPC) have been derived from findings of their differential expression patterns in NPC cell lines. Nevertheless, expression data from a comprehensive list of RP gene family members is still lacking. This paper reports the assessment of two RP genes, eL13 and eL14, with regards to their expression patterns in several NPC cell lines (TW04, TW01, HK1, HONE1 and SUNE-1) relative to a non-malignant control (NP69). A conventional Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay was employed. Analysis of eL13 has never been explored before this, whereas investigation of eL14 represents an extended study. We found a general over-expression trend of eL14 in 40% (2 of 5; TW01 and HONE-1) of the NPC cell lines studied, with higher upregulated level in only one (TW01) of them. However, this pattern of expression level is not statistically significant. Expression of eL13 was not detected in any of the cell lines used. The inconsistency of these expression patterns demonstrates an elusive nature of RP activities in the malignancy of the nasopharynx.
    Matched MeSH terms: Up-Regulation
  7. Mariani Mohd Zain, Zary Shariman Yahaya, Nik Ahmad Irwan Izzauddin Nik Him
    Trop Life Sci Res, 2016;27(11):3-8.
    MyJurnal
    To date, the ivermectin resistance in nematode parasites has been reported
    and many studies are carried out to determine the causes of this problem. A free-living
    Caenorhabditis elegans is used as a model system for this study to investigate the
    response of C. elegans to ivermectin exposure by using larval development assay. Worms
    were exposed to ivermectin at concentration from 1 ng/mL to 10 ng/mL and dimethyl
    sulphoxide (DMSO) as a control. The developments of the worms were monitored for 24,
    48, 72, and 96 hours until the worms become adults. Results indicated that worms’ growth
    began to be affected by ivermectin at a concentration of 5 ng/mL, while at the
    concentration of 6, 7, 8, 9, and 10 ng/mL, the growth of worms were inhibited compared to
    control worms. Further study of the protein expression in C. elegans should be done to
    investigate the up-regulated and down-regulated proteins involve in ivermectin resistance.
    Matched MeSH terms: Up-Regulation
  8. Tan MS, Chang SW, Cheah PL, Yap HJ
    PeerJ, 2018;6:e5285.
    PMID: 30065881 DOI: 10.7717/peerj.5285
    Although most of the cervical cancer cases are reported to be closely related to the Human Papillomavirus (HPV) infection, there is a need to study genes that stand up differentially in the final actualization of cervical cancers following HPV infection. In this study, we proposed an integrative machine learning approach to analyse multiple gene expression profiles in cervical cancer in order to identify a set of genetic markers that are associated with and may eventually aid in the diagnosis or prognosis of cervical cancers. The proposed integrative analysis is composed of three steps: namely, (i) gene expression analysis of individual dataset; (ii) meta-analysis of multiple datasets; and (iii) feature selection and machine learning analysis. As a result, 21 gene expressions were identified through the integrative machine learning analysis which including seven supervised and one unsupervised methods. A functional analysis with GSEA (Gene Set Enrichment Analysis) was performed on the selected 21-gene expression set and showed significant enrichment in a nine-potential gene expression signature, namely PEG3, SPON1, BTD and RPLP2 (upregulated genes) and PRDX3, COPB2, LSM3, SLC5A3 and AS1B (downregulated genes).
    Matched MeSH terms: Up-Regulation
  9. Razak AM, Khor SC, Jaafar F, Karim NA, Makpol S
    Genes Nutr, 2018;13:31.
    PMID: 30519366 DOI: 10.1186/s12263-018-0618-2
    Background: Several muscle-specific microRNAs (myomiRs) are differentially expressed during cellular senescence. However, the role of dietary compounds on myomiRs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on myomiRs and myogenic genes during differentiation of human myoblasts. Young and senescent human skeletal muscle myoblasts (HSMM) were treated with 50 μg/mL TRF for 24 h before and after inducing differentiation.

    Results: The fusion index and myotube surface area were higher (p 

    Matched MeSH terms: Up-Regulation
  10. Moo EK, Han SK, Federico S, Sibole SC, Jinha A, Abu Osman NA, et al.
    J Biomech, 2014 Mar 21;47(5):1004-13.
    PMID: 24480705 DOI: 10.1016/j.jbiomech.2014.01.003
    Cartilage lesions change the microenvironment of cells and may accelerate cartilage degradation through catabolic responses from chondrocytes. In this study, we investigated the effects of structural integrity of the extracellular matrix (ECM) on chondrocytes by comparing the mechanics of cells surrounded by an intact ECM with cells close to a cartilage lesion using experimental and numerical methods. Experimentally, 15% nominal compression was applied to bovine cartilage tissues using a light-transmissible compression system. Target cells in the intact ECM and near lesions were imaged by dual-photon microscopy. Changes in cell morphology (N(cell)=32 for both ECM conditions) were quantified. A two-scale (tissue level and cell level) Finite Element (FE) model was also developed. A 15% nominal compression was applied to a non-linear, biphasic tissue model with the corresponding cell level models studied at different radial locations from the centre of the sample in the transient phase and at steady state. We studied the Green-Lagrange strains in the tissue and cells. Experimental and theoretical results indicated that cells near lesions deform less axially than chondrocytes in the intact ECM at steady state. However, cells near lesions experienced large tensile strains in the principal height direction, which are likely associated with non-uniform tissue radial bulging. Previous experiments showed that tensile strains of high magnitude cause an up-regulation of digestive enzyme gene expressions. Therefore, we propose that cartilage degradation near tissue lesions may be due to the large tensile strains in the principal height direction applied to cells, thus leading to an up-regulation of catabolic factors.
    Matched MeSH terms: Up-Regulation/physiology
  11. Hor JY
    Middle East J Anaesthesiol, 2010 Oct;20(6):881-3.
    PMID: 21526679
    We report a case of cardiac arrhythmia occurring in a Guillain-Barré syndrome (GBS) patient after succinylcholine administration during third endotracheal intubation, on day 13 of illness. The probable cause of arrhythmia is succinylcholine-induced hyperkalemia. Of interest, this case demonstrated in the same patient that arrhythmia only occurred during third intubation, when duration of illness is prolonged, and not during previous two intubation episodes, despite succinylcholine was also being used. In GBS, muscle denervation resulted in up-regulation of acetylcholine receptors at neuromuscular junctions, causing the muscle cell membrane to become supersensitive to succinylcholine, leading to severe hyperkalemia and arrhythmia when succinylcholine was administered.
    Matched MeSH terms: Up-Regulation/drug effects
  12. Tay YL, Amanah A, Adenan MI, Wahab HA, Tan ML
    Sci Rep, 2019 12 24;9(1):19757.
    PMID: 31874991 DOI: 10.1038/s41598-019-56106-6
    Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.
    Matched MeSH terms: Up-Regulation/drug effects*
  13. Swain N, Samanta L, Agarwal A, Kumar S, Dixit A, Gopalan B, et al.
    Antioxid Redox Signal, 2020 03 10;32(8):504-521.
    PMID: 31691576 DOI: 10.1089/ars.2019.7828
    Aims:
    To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach.
    Results:
    Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group. Ingenuity pathway analysis (IPA) predicted suppression of oxidative phosphorylation (OXPHOS) (validated by Western blotting [WB]) along with augmentation in OS and mitochondrial dysfunction in UV. The top affected networks indicated by IPA involved heat shock proteins (HSPs: HSPA2 and HSP90B1). Their expression profile was corroborated by immunocytochemistry and WB. Hypoxia-inducible factor 1A as an upstream regulator of HSPs was predicted by MetaCore. Occurrence of reductive stress in UV spermatozoa was corroborated by thiol redox status.
    Innovation:
    This is the first evidence of a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction.
    Conclusions:
    Upregulation of antioxidant system and dysfunctional OXPHOS would have shifted the redox balance of biological redox couples (GSH/GSSG, NAD+/NADH, and NADP+/NADPH) to a more reducing state leading to reductive stress. Chronic reductive stress-induced OS may be involved in sperm dysfunction in infertile men with UV, where the role of HSPs cannot be ignored. Intervention with antioxidant therapy warrants proper prior investigation.
    Matched MeSH terms: Up-Regulation/physiology*
  14. Sim EU, Chan SL, Ng KL, Lee CW, Narayanan K
    Dis Markers, 2016;2016:5179594.
    PMID: 28018022 DOI: 10.1155/2016/5179594
    Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes' involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins.
    Matched MeSH terms: Up-Regulation*
  15. Pingguan-Murphy B, Nawi I
    Clinics (Sao Paulo), 2012 Aug;67(8):939-44.
    PMID: 22948463
    OBJECTIVES: The promotion of extracellular matrix synthesis by chondrocytes is a requisite part of an effective cartilage tissue engineering strategy. The aim of this in vitro study was to determine the effect of bi-axial cyclic mechanical loading on cell proliferation and the synthesis of glycosaminoglycans by chondrocytes in three-dimensional cultures.

    METHOD: A strain comprising 10% direct compression and 1% compressive shear was applied to bovine chondrocytes seeded in an agarose gel during two 12-hour conditioning periods separated by a 12-hour resting period.

    RESULTS: The bi-axial-loaded chondrocytes demonstrated a significant increase in glycosaminoglycan synthesis compared with samples exposed to uni-axial or no loading over the same period (p<0.05). The use of a free-swelling recovery period prior to the loading regime resulted in additional glycosaminoglycan production and a significant increase in DNA content (p<0.05), indicating cell proliferation.

    CONCLUSIONS: These results demonstrate that the use of a bi-axial loading regime results in increased matrix production compared with uni-axial loading.

    Matched MeSH terms: Up-Regulation/physiology*
  16. Goh BH, Chan CK, Kamarudin MN, Abdul Kadir H
    J Ethnopharmacol, 2014 Apr 28;153(2):375-85.
    PMID: 24613274 DOI: 10.1016/j.jep.2014.02.036
    Swietenia macrophylla King is a traditional herb used to treat various diseases including hypertension, diabetes and cancer. Previous study demonstrated its anti-tumor effect but the potential mechanisms have not been clearly defined. The current study was to further investigate the underlying mechanism of ethyl acetate fraction of Swietenia macrophylla (SMEAF)-induced anti-proliferative effect and apoptosis in HCT116 colorectal carcinoma cell.
    Matched MeSH terms: Up-Regulation/drug effects; Up-Regulation/physiology
  17. Jiang L, Hindmarch CC, Rogers M, Campbell C, Waterfall C, Coghill J, et al.
    Sci Rep, 2016 10 24;6:35671.
    PMID: 27774996 DOI: 10.1038/srep35671
    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or 'podocytes', the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes.
    Matched MeSH terms: Up-Regulation/drug effects; Up-Regulation/genetics
  18. Arockiaraj J, Bhatt P, Kumaresan V, Dhayanithi NB, Arshad A, Harikrishnan R, et al.
    Fish Shellfish Immunol, 2015 Nov;47(1):221-30.
    PMID: 26363233 DOI: 10.1016/j.fsi.2015.09.015
    In this study, we reported a molecular characterization of three CC chemokines namely, CsCC-Chem14, CsCC-Chem20 and CsCC-Chem25 which are were identified from the established cDNA library of striped murrel Channa striatus. Multiple sequence alignment of all the three chemokines revealed the presence of gene specific domains and motifs including small cytokine domain, IL8 like domain, receptor binding site and glycosaminoglycan (GAG) binding sites. Three dimensional structures of the chemokines under study showed an important facet on their anti-microbial property. Tissue specific mRNA expression showed that the CsCC-Chem14 is highly expressed in spleen, CsCC-Chem20 in liver and CsCC-Chem25 in trunk kidney. On challenge C. striatus with oomycete fungus Aphanomyces invadans, both CsCC-Chem20 and CsCC-Chem25 showed significant (P < 0.05) up-regulation compared to CsCC-Chem14. The increase in the expression levels of CsCC-Chem20 and CsCC-Chem25 due to infection showed that they are antimicrobial proteins. But considering the CsCC-Chem14 expression, it is found to be a constitutive chemokine and is involved in homeostatic function in spleen of C. striatus. C. striatus challenged with bacteria Aeromonas hydrophila also exhibited different up-regulation pattern in all the three chemokines at various time points. However, extensive studies are required to determine the functional activities of CsCC-Chem14, CsCC-Chem20 and CsCC-Chem25 in vitro and in vivo to gain more knowledge at the molecular and proteomic levels.
    Matched MeSH terms: Up-Regulation
  19. Samie N, Muniandy S, Kanthimathi MS, Haerian BS, Azudin RE
    Sci Rep, 2016 Apr 13;6:24172.
    PMID: 27072064 DOI: 10.1038/srep24172
    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.
    Matched MeSH terms: Up-Regulation
  20. Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.
    Sci Rep, 2016 05 10;6:25650.
    PMID: 27160553 DOI: 10.1038/srep25650
    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
    Matched MeSH terms: Up-Regulation
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