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Dysregulation of miR-31 and miR-375 expression is associated with clinical outcomes in oral carcinoma

Siow MY, Ng LP, Vincent-Chong VK, Jamaludin M, Abraham MT, Abdul Rahman ZA, et al.

Oral Dis, 2014 May;20(4):345-51.
PMID: 23651447 DOI: 10.1111/odi.12118

To identify differentially expressed miRNA between oral squamous cell carcinoma (OSCC) and non-cancer (NC) and to associate these with clinico-pathological parameters.

Matched MeSH terms: Gene Expression Regulation, Neoplastic
Genome-wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11

Vincent-Chong VK, Ismail SM, Rahman ZA, Sharifah NA, Anwar A, Pradeep PJ, et al.

Oral Dis, 2012 Jul;18(5):469-76.
PMID: 22251088 DOI: 10.1111/j.1601-0825.2011.01894.x

Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression.

Matched MeSH terms: Gene Expression Regulation, Neoplastic; Gene Expression Profiling
Caveolin 1 (Cav-1) and actin-related protein 2/3 complex, subunit 1B (ARPC1B) expressions as prognostic indicators for oral squamous cell carcinoma (OSCC)

Auzair LB, Vincent-Chong VK, Ghani WM, Kallarakkal TG, Ramanathan A, Lee CE, et al.

Eur Arch Otorhinolaryngol, 2016 Jul;273(7):1885-93.
PMID: 26138391 DOI: 10.1007/s00405-015-3703-9

Caveolin-1 (Cav-1) and Actin-Related Protein 2/3 Complex, Subunit 1B (ARPC1B) have been implicated in various human cancers, yet its role in tumorigenesis remains controversial. Therefore, this study aims to determine the protein expression of these two genes in oral squamous cell carcinomas (OSCCs) and to evaluate the clinical and prognostic impact of these genes in OSCC. Protein expressions of these two genes were determined by immunohistochemistry technique. The association between Cav-1 and ARPC1B with clinico-pathological parameters was evaluated by Chi-square test (or Fisher exact test where appropriate). Correlation between the protein expressions of these 2 genes with survival was analyzed using Kaplan-Meier and Cox regression models. Cav-1 and ARPC1B were found to be significantly over-expressed in OSCC compared to normal oral mucosa (p = 0.002 and p = 0.033, respectively). Low level of ARPC1B protein expression showed a significant correlation with lymph node metastasis (LNM) (p = 0.010) and advanced tumor staging (p = 0.003). Kaplan-Meier survival analyses demonstrated that patients with over-expression of Cav-1 protein were associated with poor prognosis (p = 0.030). Adjusted multivariate Cox regression model revealed that over-expression of Cav-1 remained as an independent significant prognostic factor for OSCC (HRR = 2.700, 95 % CI 1.013-7.198, p = 0.047). This study demonstrated that low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients.

Matched MeSH terms: Gene Expression Regulation, Neoplastic*
Fulltext A genetic programming approach to oral cancer prognosis

Tan MS, Tan JW, Chang SW, Yap HJ, Abdul Kareem S, Zain RB

PeerJ, 2016;4:e2482.
PMID: 27688975 DOI: 10.7717/peerj.2482

The potential of genetic programming (GP) on various fields has been attained in recent years. In bio-medical field, many researches in GP are focused on the recognition of cancerous cells and also on gene expression profiling data. In this research, the aim is to study the performance of GP on the survival prediction of a small sample size of oral cancer prognosis dataset, which is the first study in the field of oral cancer prognosis.

Matched MeSH terms: Gene Expression Profiling
Fulltext Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

Vincent-Chong VK, Salahshourifar I, Woo KM, Anwar A, Razali R, Gudimella R, et al.

PLoS One, 2017;12(4):e0174865.
PMID: 28384287 DOI: 10.1371/journal.pone.0174865

BACKGROUND: Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy.
OBJECTIVES: The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes.
MATERIALS AND METHODS: Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software.
RESULTS: Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC.
CONCLUSION: Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways.

Matched MeSH terms: Gene Expression Profiling*
Fulltext Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats

Yida Z, Imam MU, Ismail M, Ooi DJ, Sarega N, Azmi NH, et al.

J Diabetes Res, 2015;2015:760535.
PMID: 26273674 DOI: 10.1155/2015/760535

Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance.

Matched MeSH terms: Gene Expression Regulation
Disruption of MAPK1 expression in the ERK signalling pathway and the RUNX1‑RUNX1T1 fusion gene attenuate the differentiation and proliferation and induces the growth arrest in t(8;21) leukaemia cells

Bashanfer SAA, Saleem M, Heidenreich O, Moses EJ, Yusoff NM

Oncol Rep, 2019 Mar;41(3):2027-2040.
PMID: 30569130 DOI: 10.3892/or.2018.6926

The t(8;21) translocation is one of the most frequent chromosome abnormalities associated with acute myeloid leukaemia (AML). This abberation deregulates numerous molecular pathways including the ERK signalling pathway among others. Therefore, the aim of the present study was to investigate the gene expression patterns following siRNA‑mediated suppression of RUNX1‑RUNX1T1 and MAPK1 in Kasumi‑1 and SKNO‑1 cells and to determine the differentially expressed genes in enriched biological pathways. BeadChip microarray and gene ontology analysis revealed that RUNX1‑RUNX1T1 and MAPK1 suppression reduced the proliferation rate of the t(8;21) cells with deregulated expression of several classical positive regulator genes that are otherwise known to enhance cell proliferation. RUNX1‑RUNX1T1 suppression exerted an anti‑apoptotic effect through the overexpression of BCL2, BIRC3 and CFLAR genes, while MAPK1 suppression induced apopotosis in t(8;21) cells by the apoptotic mitochondrial changes stimulated by the activity of upregulated TP53 and TNFSF10, and downregulated JUN gene. RUNX1‑RUNX1T1 suppression supported myeloid differentiation by the differential expression of CEBPA, CEBPE, ID2, JMJD6, IKZF1, CBFB, KIT and CDK6, while MAPK1 depletion inhibited the differentiation of t(8;21) cells by elevated expression of ADA and downregulation of JUN. RUNX1‑RUNX1T1 and MAPK1 depletion induced cell cycle arrest at the G0/G1 phase. Accumulation of cells in the G1 phase was largely the result of downregulated expression of TBRG4, CCNE2, FOXO4, CDK6, ING4, IL8, MAD2L1 and CCNG2 in the case of RUNX1‑RUNX1T1 depletion and increased expression of RASSF1, FBXO6, DADD45A and P53 in the case of MAPK1 depletion. Taken together, the current results demonstrate that MAPK1 promotes myeloid cell proliferation and differentiation simultaneously by cell cycle progression while suppresing apoptosis.

Matched MeSH terms: Gene Expression Regulation, Leukemic*; Gene Expression Profiling
Immunogenic properties of recombinant ectodomain of Newcastle disease virus hemagglutinin-neuraminidase protein expressed in Escherichia coli

Wong SK, Tan WS, Omar AR, Tan CS, Yusoff K

Acta Virol., 2009;53(1):35-41.
PMID: 19301949

Hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) plays a vital role in the viral infectivity, host immunity, and disease diagnosis. A portion of the HN gene encoding the ectodomain (nt 142-1739) was cloned and expressed in Escherichia coli yielding an insoluble HN protein and a soluble NusA-HN protein containing N-utilization substance A (NusA) fusion component. Both recombinant proteins were purified and used for immunization of chickens. The recombinant HN protein induced higher antibody titers as compared to the recombinant NusA-HN protein. These antibodies were able to react in immunoblot analysis with the corresponding recombinant proteins as well as with the HN protein of NDV.

Matched MeSH terms: Gene Expression
Recombinant Newcastle Disease virus capsids displaying enterovirus 71 VP1 fragment induce a strong immune response in rabbits

Sivasamugham LA, Cardosa MJ, Tan WS, Yusoff K

J Med Virol, 2006 Aug;78(8):1096-104.
PMID: 16789020

The complete VP1 protein of EV71 was truncated into six segments and fused to the C-terminal ends of full-length nucleocapsid protein (NPfl) and truncated NP (NPt; lacks 20% amino acid residues from its C-terminal end) of newcastle disease virus (NDV). Western blot analysis using anti-VP1 rabbit serum showed that the N-terminal region of the VP1 protein contains a major antigenic region. The recombinant proteins carrying the truncated VP1 protein, VP1(1-100), were expressed most efficiently in Escherichia coli as determined by Western blot analysis. Electron microscopic analysis of the purified recombinant protein, NPt-VP(1-100) revealed that it predominantly self-assembled into intact ring-like structures whereas NPfl-VP(1-100) recombinant proteins showed disrupted ring-like formations. Rabbits immunized with the purified NPt-VP(1-100) and NPfl-VP(1-100) exhibited a strong immune response against the complete VP1 protein. The antisera of these recombinant proteins also reacted positively with authentic enterovirus 71 and the closely related Coxsackievirus A16 when analyzed by an immunofluorescence assay suggesting their potential as immunological reagents for the detection of anti-enterovirus 71 antibodies in serum samples.

Matched MeSH terms: Gene Expression Regulation, Viral
Cloning and expression of the phosphoprotein gene of Newcastle disease virus in Escherichia coli

Kho CL, Tan WS, Yusoff K

J. Biochem. Mol. Biol. Biophys., 2002 Apr;6(2):117-21.
PMID: 12186767

The phosphoprotein (P) gene of a heat stable Newcastle disease virus (NDV) was cloned, sequenced and expressed in Escherichia coli. SDS-PAGE analysis of the recombinant P protein (395 amino acids) and a C-terminal extension derivative (424 amino acids), gave rise to two distinct protein bands with molecular masses of approximately 53-55 and 56-58 kDa, respectively, which are approximately 26-30% heavier than those calculated from the deduced amino acid sequences. The differences in molecular mass on SDS-PAGE are thought to be attributed to the acidic nature of the P protein (pI=6.27) and also the different degrees of phosphorylation in the prokaryotic cell. Amino acid sequence comparison of the P protein among the published NDV strains showed that they were highly conserved particularly at the putative phosphorylation sites.

Matched MeSH terms: Gene Expression
Lactobacillus acidophilus as a live vehicle for oral immunization against chicken anemia virus

Moeini H, Rahim RA, Omar AR, Shafee N, Yusoff K

Appl Microbiol Biotechnol, 2011 Apr;90(1):77-88.
PMID: 21181148 DOI: 10.1007/s00253-010-3050-0

The AcmA binding domains of Lactococcus lactis were used to display the VP1 protein of chicken anemia virus (CAV) on Lactobacillus acidophilus. One and two repeats of the cell wall binding domain of acmA gene were amplified from L. lactis MG1363 genome and then inserted into co-expression vector, pBudCE4.1. The VP1 gene of CAV was then fused to the acmA sequences and the VP2 gene was cloned into the second MCS of the same vector before transformation into Escherichia coli. The expressed recombinant proteins were purified using a His-tag affinity column and mixed with a culture of L. acidophilus. Whole cell ELISA and immunofluorescence assay showed the binding of the recombinant VP1 protein on the surface of the bacterial cells. The lactobacilli cells carrying the CAV VP1 protein were used to immunize specific pathogen-free chickens through the oral route. A moderate level of neutralizing antibody to CAV was detected in the serum of the immunized chickens. A VP1-specific proliferative response was observed in splenocytes of the chickens after oral immunization. The vaccinated groups also showed increased levels of Th1 cytokines interleukin (IL)-2, IL-12, and IFN-γ. These observations suggest that L. acidophilus can be used in the delivery of vaccines to chickens.

Matched MeSH terms: Gene Expression
Fulltext Proof of concept in utilizing in-trans surface display system of Lactobacillus plantarum as mucosal tuberculosis vaccine via oral administration in mice

Mustafa AD, Kalyanasundram J, Sabidi S, Song AA, Abdullah M, Abdul Rahim R, et al.

BMC Biotechnol, 2018 10 11;18(1):63.
PMID: 30309359 DOI: 10.1186/s12896-018-0461-y

BACKGROUND: Tuberculosis is one of the most common and deadliest infectious diseases worldwide affecting almost a third of the world's population. Although this disease is being prevented and controlled by the Bacille Calmette Guérin (BCG) vaccine, the protective efficacy is highly variable and substandard (0-80%) in adults. Therefore, novel and effective tuberculosis vaccine that can overcome the limitations from BCG vaccine need to be developed.
RESULTS: A novel approach of utilizing an in-trans protein surface display system of Lactobacillus plantarum carrying and displaying combination of Mycobacterium tuberculosis subunit epitope antigens (Ag85B, CFP-10, ESAT-6, Rv0475 and Rv2031c) fused with LysM anchor motif designated as ACERL was constructed, cloned and expressed in Esherichia coli Rossetta expression host. Subsequently the binding capability of ACERL to the cell wall of L. plantarum was examined via the immunofluorescence microscopy and whole cell ELISA where successful attachment and consistent stability of cell wall binding up to 4 days was determined. The immunization of the developed vaccine of L. plantarum surface displaying ACERL (Lp ACERL) via the oral route was studied in mice for its immunogenicity effects. Lp ACERL immunization was able to invoke significant immune responses that favor the Th1 type cytokine response of IFN-γ, IL-12 and IL-2 as indicated by the outcome from the cytokine profiling of spleen, lung, gastrointestinal tract (GIT), and the re-stimulation of the splenocytes from the immunized mice. Co-administration of an adjuvant consisting of Lactococcus lactis secreting mouse IL-12 (LcIL-12) with Lp ACERL was also investigated. It was shown that the addition of LcIL-12 was able to further generate significant Th1 type cytokines immune responses, similar or better than that of Lp ACERL alone which can be observed from the cytokine profiling of the immunized mice's spleen, lung and GIT.
CONCLUSIONS: This study represents a proof of concept in the development of L. plantarum as a carrier for a non-genetically modified organism (GMO) tuberculosis vaccine, which may be the strategy in the future for tuberculosis vaccine development.

Matched MeSH terms: Gene Expression
Fulltext Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells

Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA

Nutr J, 2015;14:31.
PMID: 25889965 DOI: 10.1186/s12937-015-0015-2

The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29.

Matched MeSH terms: Gene Expression/drug effects
Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against chikungunya virus

Rothan HA, Bahrani H, Shankar EM, Rahman NA, Yusof R

Antiviral Res, 2014 Aug;108:173-80.
PMID: 24929084 DOI: 10.1016/j.antiviral.2014.05.019

Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.

Matched MeSH terms: Gene Expression
All serotypes of dengue virus induce HLA-A2 major histocompatibility complex class I promoter activity in human liver cells

Othman S, Rahman NA, Yusof R

Trans R Soc Trop Med Hyg, 2010 Dec;104(12):806-8.
PMID: 20800252 DOI: 10.1016/j.trstmh.2010.07.004

In contrast to many viruses that escape the host's immune responses by suppressing the major histocompatibility complex (MHC) class I pathway, flaviviruses have been shown to up-regulate the cell surface expression of MHC class I complex. The mechanism by which dengue virus (DV) achieves this up-regulation remains unclear. Our investigation on the HLA-A2 gene in human liver cells demonstrated that all four serotypes of dengue virus, DV1 to DV4, resulted in variable degrees of promoter induction. This illustrates the importance of MHC class I transcription regulation in primary infections by different DV serotypes that may have even greater impact in secondary infections, associated with increased disease severity.

Matched MeSH terms: Gene Expression Regulation
Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NFκB binding domains of the Class I Regulatory Complex

Othman S, Rahman NA, Yusof R

Virus Res, 2012 Jan;163(1):238-45.
PMID: 22001567 DOI: 10.1016/j.virusres.2011.09.040

Despite aggressive efforts in dengue research, the control of dengue diseases and discovery of therapeutics against them await complete elucidation of its complex immune-pathogenesis. Unlike many viruses that escape the host's immune responses by suppressing the major histocompatibility complex (MHC) Class I pathway, many Flaviviruses up-regulate the cell surface expression of MHC Class I complex. We recently reported MHC Class I HLA-A2 promoter activation by all serotypes of dengue virus (DV). The mechanism by which DV regulates this is further explored here in HepG2 human liver cell line. Using real-time PCR, evidence that, similar to infections by other Flaviviruses, DV infection has the ability to up-regulate the MHC Class I transcription and mRNA synthesis, is presented. The region responsive towards DV infection of all serotypes was mapped to the Class I Regulatory Complex (CRC) of the HLA-A2 promoter. Competition electrophoretic mobility shift assay (EMSA) with NFκB probe established the presence of specific DNA-protein complex in DV-infected nuclear extracts. Antibody-supershift assays identified the MHC Class I promoter activation by DV to occur through binding of p65/p50 heterodimers and p65 homodimers to κB1 and κB2 cis-acting elements, respectively, within the CRC, and not with the interferon consensus sequence (ICS). This study presents evidence of MHC Class I gene modulation by DV, hence providing a better understanding of dengue immune-pathogenesis that would consequently facilitate the discovery of antiviral therapeutics against dengue.

Matched MeSH terms: Gene Expression Profiling
Fulltext Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication

Rothan HA, Bahrani H, Mohamed Z, Abd Rahman N, Yusof R

PLoS One, 2014;9(4):e94561.
PMID: 24722532 DOI: 10.1371/journal.pone.0094561

Dengue virus (DENV) broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1) and plectasin (PLSN) were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN) as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro) with half-maximal inhibitory concentration (IC50) 0.5±0.1 μM. The real-time proliferation assay (RTCA) and the end-point proliferation assay (MTT assay) showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.

Matched MeSH terms: Gene Expression
Are ERM (ezrin/radixin/moesin) proteins targets for autoantibodies in demyelinating neuropathies?

Miyaji K, Shahrizaila N, Umapathi T, Chan YC, Hirata K, Yuki N

Hum Immunol, 2014 Nov;75(11):1089-91.
PMID: 25286001 DOI: 10.1016/j.humimm.2014.09.010

Ezrin, radixin and moesin, which are strongly expressed in the Schwann cell microvilli, are putative targets for autoantibodies in acute or chronic inflammatory demyelinating polyneuropathy (AIDP or CIDP). An association between anti-moesin IgG antibodies and cytomegalovirus-related AIDP has been postulated. None of 41 AIDP patients, including 8 cytomegalovirus-related AIDP patients, and 23 CIDP had IgG or IgM antibodies to ezrin, radixin and moesin; whereas, one patient with cytomegalovirus-related AIDP had anti-ezrin IgM antibodies. Ezrin, radixin and moesin are unlikely targets for autoantibodies in AIDP and CIDP, and the association of anti-moesin antibodies with cytomegalovirus-related AIDP was not confirmed.

Matched MeSH terms: Gene Expression
Fulltext TRANSPARENT TESTA GLABRA1 Regulates the Accumulation of Seed Storage Reserves in Arabidopsis

Chen M, Zhang B, Li C, Kulaveerasingam H, Chew FT, Yu H

Plant Physiol, 2015 Sep;169(1):391-402.
PMID: 26152712 DOI: 10.1104/pp.15.00943

Seed storage reserves mainly consist of starch, triacylglycerols, and storage proteins. They not only provide energy for seed germination and seedling establishment, but also supply essential dietary nutrients for human beings and animals. So far, the regulatory networks that govern the accumulation of seed storage reserves in plants are still largely unknown. Here, we show that TRANSPARENT TESTA GLABRA1 (TTG1), which encodes a WD40 repeat transcription factor involved in many aspects of plant development, plays an important role in mediating the accumulation of seed storage reserves in Arabidopsis (Arabidopsis thaliana). The dry weight of ttg1-1 embryos significantly increases compared with that of wild-type embryos, which is accompanied by an increase in the contents of starch, total protein, and fatty acids in ttg1-1 seeds. FUSCA3 (FUS3), a master regulator of seed maturation, binds directly to the TTG1 genomic region and suppresses TTG1 expression in developing seeds. TTG1 negatively regulates the accumulation of seed storage proteins partially through transcriptional repression of 2S3, a gene encoding a 2S albumin precursor. TTG1 also indirectly suppresses the expression of genes involved in either seed development or synthesis/modification of fatty acids in developing seeds. In addition, we demonstrate that the maternal allele of the TTG1 gene suppresses the accumulation of storage proteins and fatty acids in seeds. Our results suggest that TTG1 is a direct target of FUS3 in the framework of the regulatory hierarchy controlling seed filling and regulates the accumulation of seed storage proteins and fatty acids during the seed maturation process.

Matched MeSH terms: Gene Expression Regulation, Plant
scGGAN: single-cell RNA-seq imputation by graph-based generative adversarial network

Huang Z, Wang J, Lu X, Mohd Zain A, Yu G

Brief Bioinform, 2023 Mar 19;24(2).
PMID: 36733262 DOI: 10.1093/bib/bbad040

Single-cell RNA sequencing (scRNA-seq) data are typically with a large number of missing values, which often results in the loss of critical gene signaling information and seriously limit the downstream analysis. Deep learning-based imputation methods often can better handle scRNA-seq data than shallow ones, but most of them do not consider the inherent relations between genes, and the expression of a gene is often regulated by other genes. Therefore, it is essential to impute scRNA-seq data by considering the regional gene-to-gene relations. We propose a novel model (named scGGAN) to impute scRNA-seq data that learns the gene-to-gene relations by Graph Convolutional Networks (GCN) and global scRNA-seq data distribution by Generative Adversarial Networks (GAN). scGGAN first leverages single-cell and bulk genomics data to explore inherent relations between genes and builds a more compact gene relation network to jointly capture the homogeneous and heterogeneous information. Then, it constructs a GCN-based GAN model to integrate the scRNA-seq, gene sequencing data and gene relation network for generating scRNA-seq data, and trains the model through adversarial learning. Finally, it utilizes data generated by the trained GCN-based GAN model to impute scRNA-seq data. Experiments on simulated and real scRNA-seq datasets show that scGGAN can effectively identify dropout events, recover the biologically meaningful expressions, determine subcellular states and types, improve the differential expression analysis and temporal dynamics analysis. Ablation experiments confirm that both the gene relation network and gene sequence data help the imputation of scRNA-seq data.

Matched MeSH terms: Gene Expression Profiling

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