Displaying publications 1 - 20 of 54 in total

Abstract:
Sort:
  1. Fulltext Co-application of a biosolids product and biochar to two coarse-textured pasture soils influenced microbial N cycling genes and potential for N leaching
    Shanmugam S, Jenkins SN, Mickan BS, Jaafar NM, Mathes F, Solaiman ZM, et al.
    Sci Rep, 2021 01 13;11(1):955.
    PMID: 33441591 DOI: 10.1038/s41598-020-78843-9
    Co-application of biochar and biosolids to soil has potential to mitigate N leaching due to physical and chemical properties of biochar. Changes in N cycling pathways in soil induced by co-application of biological amendments could further mitigate N loss, but this is largely unexplored. The aim of this study was to determine whether co-application of a biochar and a modified biosolids product to three pasture soils differing in texture could alter the relative abundance of N cycling genes in soil sown with subterranean clover. The biosolids product contained lime and clay and increased subterranean clover shoot biomass in parallel with increases in soil pH and soil nitrate. Its co-application with biochar similarly increased plant growth and soil pH with a marked reduction in nitrate in two coarse textured soils but not in a clayey soil. While application of the biosolids product altered in silico predicted N cycling functional genes, there was no additional change when applied to soil in combination with biochar. This supports the conclusion that co-application of the biochar and biosolids product used here has potential to mitigate loss of N in coarse textured soils due to N adsoption by the biochar and independently of microbial N pathways.
    Matched MeSH terms: Signal Transduction/genetics
  2. Fulltext Differential expression of basal microRNAs' patterns in human dental pulp stem cells
    Vasanthan P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Musa S, Abu Kasim NH
    J Cell Mol Med, 2015 Mar;19(3):566-80.
    PMID: 25475098 DOI: 10.1111/jcmm.12381
    MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real-time PCR. Notably, we observed 19 up-regulated miRNAs and 29 significantly down-regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM-MSCs). The 19 up-regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa-miR-516a-3p, hsa-miR-125b-1-3p, hsa-miR-221-5p, hsa-miR-7, hsa-miR-584-5p, hsa-miR-190a, hsa-miR-106a-5p, hsa-mir-376a-5p, hsa-mir-377-5p and hsa-let-7f-2-3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa-miR-516a-3p and hsa-miR-7-5p as these miRNAs were highly expressed upon validation with qRT-PCR analysis. We further proceeded with loss-of-function analysis with these miRNAs and we observed that hsa-miR-516a-3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa-miR-7-5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa-miR-516a-3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs.
    Matched MeSH terms: Signal Transduction/genetics
  3. Effects of cell cycle phases on the induction of dental pulp stem cells toward dopaminergic-like cells
    Gnanasegaran N, Govindasamy V, Kathirvaloo P, Musa S, Abu Kasim NH
    J Tissue Eng Regen Med, 2018 02;12(2):e881-e893.
    PMID: 28079995 DOI: 10.1002/term.2401
    Parkinson's disease (PD) is characterized by tremors and cognitive issues, and is due to the death of dopaminergic (DA-ergic) neurons in brain circuits that are responsible for producing neurotransmitter dopamine (DA). Currently, cell replacement therapies are underway to improve upon existing therapeutic approaches such as drug treatments and electrical stimulation. Among the widely available sources, dental pulp stem cells (DPSCs) from deciduous teeth have gained popularity because of their neural crest origin and inherent propensity toward neuronal lineage. Despite the various pre-clinical studies conducted, an important factor yet to be elucidated is the influence of growth phases in a typical trans-differentiation process. This study selected DPSCs at three distinct time points with variable growth phase proportions (G0/G1, S and G2/M) for in vitro trans-differentiation into DA-ergic-like cells. Using commercially available PCR arrays, we identified distinct gene profiles pertaining to cell cycles in these phases. The differentiation outcomes were assessed in terms of morphology and gene and protein expression, as well as with functional assays. It was noted that DPSCs with the highest G0/G1 phase were comparatively the best, representing at least a 2-fold up regulation (p 
    Matched MeSH terms: Signal Transduction/genetics
  4. Fulltext Thymoquinone Induces Downregulation of BCR-ABL/JAK/STAT Pathway and Apoptosis in K562 Leukemia Cells
    Al-Rawashde FA, Wan Taib WR, Ismail I, Johan MF, Al-Wajeeh AS, Al-Jamal HAN
    Asian Pac J Cancer Prev, 2021 Dec 01;22(12):3959-3965.
    PMID: 34967577 DOI: 10.31557/APJCP.2021.22.12.3959
    OBJECTIVE: BCR ABL oncogene encodes the BCR-ABL chimeric protein, which is a constitutively activated non-receptor tyrosine kinase. The BCR-ABL oncoprotein is a key molecular basis for the pathogenesis of chronic myeloid leukemia (CML) via activation of several downstream signaling pathways including JAK/STAT pathway. Development of leukemia involves constitutive activation of signaling molecules including, JAK2, STAT3, STAT5A and STAT5B. Thymoquinone (TQ) is a bioactive constituent of Nigella sativa that has shown anticancer properties in various cancers. The present study aimed to evaluate the effect of TQ on the expression of BCR ABL, JAK2, STAT3, STAT5A and STAT5B genes and their consequences on the cell proliferation and apoptosis in K562 CML cells.

    METHODS: BCR-ABL positive K562 CML cells were treated with TQ. Cytotoxicity was determined by Trypan blue exclusion assay. Apoptosis assay was performed by annexin V-FITC/PI staining assay and analyzed by flow cytometry. Transcription levels of BCR ABL, JAK2, STAT3, STAT5A and STAT5B genes were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Protein levels of JAK2 and STAT5 were determined by Jess Assay analysis.

    RESULTS: TQ markedly decreased the cell proliferation and induced apoptosis in K562 cells (P < 0.001) in a concentration dependent manner. TQ caused a significant decrease in the transcriptional levels of BCR ABL, JAK2, STAT3, STAT5A and STAT5B genes (P < 0.001). TQ induced a significant decrease in JAK2 and STAT5 protein levels (P < 0.001).

    CONCLUSION: our results indicated that TQ inhibited cell growth of K562 cells via downregulation of BCR ABL/ JAK2/STAT3 and STAT5 signaling and reducing JAK2 and STAT5 protein levels.

    Matched MeSH terms: Signal Transduction/genetics
  5. Fulltext Draft genome sequence of the rubber tree Hevea brasiliensis
    Rahman AY, Usharraj AO, Misra BB, Thottathil GP, Jayasekaran K, Feng Y, et al.
    BMC Genomics, 2013;14:75.
    PMID: 23375136 DOI: 10.1186/1471-2164-14-75
    Hevea brasiliensis, a member of the Euphorbiaceae family, is the major commercial source of natural rubber (NR). NR is a latex polymer with high elasticity, flexibility, and resilience that has played a critical role in the world economy since 1876.
    Matched MeSH terms: Signal Transduction/genetics
  6. Fulltext FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures
    Wong KK, Gascoyne DM, Soilleux EJ, Lyne L, Spearman H, Roncador G, et al.
    Oncotarget, 2016 Aug 16;7(33):52940-52956.
    PMID: 27224915 DOI: 10.18632/oncotarget.9507
    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
    Matched MeSH terms: Signal Transduction/genetics
  7. Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration
    Salleh MN, Ismail P, Abdullah AS, Taufiq-Yap YH, Carmichael P
    IUBMB Life, 2004 Jul;56(7):409-16.
    PMID: 15545218
    Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.
    Matched MeSH terms: Signal Transduction/genetics
  8. Fulltext Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway
    Chai AWY, Yee PS, Price S, Yee SM, Lee HM, Tiong VK, et al.
    Elife, 2020 09 29;9.
    PMID: 32990596 DOI: 10.7554/eLife.57761
    New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non-essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets. We validate a distinctive dependency on YAP1 and WWTR1 of the Hippo pathway, where the lost-of-fitness effect of one paralog can be compensated only in a subset of lines. We also discover that OSCCs with WWTR1 dependency signature are significantly associated with biomarkers of favorable response toward immunotherapy. In summary, we have delineated the genetic vulnerabilities of OSCC, enabling the prioritization of therapeutic targets for further exploration, including the targeting of YAP1 and WWTR1.
    Matched MeSH terms: Signal Transduction/genetics*
  9. Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha (PPARα) in human hepatocarcinoma HepG2 cells by activation of NF-κB pathway
    Lim WS, Ng DL, Kor SB, Wong HK, Tengku-Muhammad TS, Choo QC, et al.
    Cytokine, 2013 Jan;61(1):266-74.
    PMID: 23141142 DOI: 10.1016/j.cyto.2012.10.007
    Peroxisome proliferator activated receptor-alpha (PPARα) plays a major role in the regulation of lipid and glucose homeostasis, and inflammatory responses. The objectives of the study were to systematically investigate the effects of TNF-α and its regulatory pathway on PPARα expression in HepG2 cells using Real-Time RT-PCR and western blot analysis. Here, TNF-α suppressed PPARα mRNA expression in a dose- and time-dependent manner at the level of gene transcription. Pre-treatment of cells with 10μM of Wedelolactone for 2h was sufficient to restore PPARα expression to basal levels and also affected the expression of PPARα-regulated genes. This study also demonstrated that TNF-α represses PPARα expression by augmenting the activity of canonical NF-κB signalling pathway. This was shown by the abrogation of TNF-α-mediated PPARα down-regulation, after both p65 and p50 were knocked down via siRNA. The IKK contributes to IκBα degradation and mediates inducible phosphorylation of p105 at Ser933. Surprisingly, phosphorylation of p65 at Ser468 and Ser536 were severely abrogated with Wedelolactone inhibition, suggesting that Ser468 and Ser536, but not Ser276, may mediate the TNF-α inhibitory action on PPARα gene expression. These results suggest that TNF-α might, at least in part, suppress PPARα expression through activation of IKK/p50/p105/p65 pathway. Furthermore, phosphorylation of p65 at Ser468 and Ser536 may play a crucial role in the mechanism that limits PPARα production in the human HepG2 cells.
    Matched MeSH terms: Signal Transduction/genetics
  10. Fulltext MicroRNA-362 negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling to suppress cell migration and invasion
    Cheng HP, Huang CJ, Tsai ML, Ong HT, Cheong SK, Choo KB, et al.
    Int J Med Sci, 2021;18(8):1798-1809.
    PMID: 33746597 DOI: 10.7150/ijms.50871
    Cell migration and invasion are modulated by epithelial-to-mesenchymal transition (EMT) and the reverse MET process. Despite the detection of microRNA-362 (miR-362, both the miR-362-5p and -3p species) in cancers, none of the identified miR-362 targets is a mesenchymal or epithelial factor to link miR-362 with EMT/MET and metastasis. Focusing on the TGF-β/SMAD signaling pathway in this work, luciferase assays and western blot data showed that miR-362 targeted and negatively regulated expression of SMAD4 and E-cadherin, but not SNAI1, which is regulated by SMAD4. However, miR-362 knockdown also down-regulated SMAD4 and SNAI1, but up-regulated E-cadherin expression. Wound-healing and transwell assays further showed that miR-362 knockdown suppressed cell migration and invasion, effects which were reversed by over-expressing SMAD4 or SNAI1, or by knocking down E-cadherin in the miR-362 knockdown cells. In orthotopic mice, miR-362 knockdown inhibited metastasis, and displayed the same SMAD4 and E-cadherin expression profiles in the tumors as in the in vitro studies. A scheme is proposed to integrate miR-362 negative regulation via SMAD4, and to explain miR-362 positive regulation of SMAD4 via miR-362 targeting of known SMAD4 suppressors, BRK and DACH1, which would have resulted in SMAD4 depletion and annulment of subsequent involvement in TGF-β signaling actions. Hence, miR-362 both negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling pathway to suppress cell motility and invasiveness and metastasis, and may explain the reported clinical association of anti-miR-362 with suppressed metastasis in various cancers. MiR-362 knockdown in miR-362-positive cancer cells may be used as a therapeutic strategy to suppress metastasis.
    Matched MeSH terms: Signal Transduction/genetics
  11. Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy
    Ricos MG, Hodgson BL, Pippucci T, Saidin A, Ong YS, Heron SE, et al.
    Ann Neurol, 2016 Jan;79(1):120-31.
    PMID: 26505888 DOI: 10.1002/ana.24547
    Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3, also contribute to cases of focal epilepsy.
    Matched MeSH terms: Signal Transduction/genetics*
  12. Dietary non-nutritive factors in targeting of regulatory molecules in colorectal cancer: an update
    Pandurangan AK, Esa NM
    Asian Pac J Cancer Prev, 2013;14(10):5543-52.
    PMID: 24289544
    Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), Wnt/β-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.
    Matched MeSH terms: Signal Transduction/genetics*
  13. Identification of immune response-related genes and signalling pathways in spleen of Vibrio parahaemolyticus-infected Epinephelus fuscoguttatus (Forskal) by next-generation sequencing
    Low CF, Mariana NS, Maha A, Chee HY, Fatimah MY
    J Fish Dis, 2016 Mar;39(3):389-94.
    PMID: 25786532 DOI: 10.1111/jfd.12359
    Matched MeSH terms: Signal Transduction/genetics*
  14. A review on epidermal growth factor receptor's role in breast and non-small cell lung cancer
    Subramaniyan V, Fuloria S, Gupta G, Kumar DH, Sekar M, Sathasivam KV, et al.
    Chem Biol Interact, 2022 Jan 05;351:109735.
    PMID: 34742684 DOI: 10.1016/j.cbi.2021.109735
    Epithelial growth factor receptor (EGFR) is a cell surface transmembrane receptor that mediates the tyrosine signaling pathway to carry the extracellular messages inside the cell and thereby alter the function of nucleus. This leads to the generation of various protein products to up or downregulate the cellular function. It is encoded by cell erythroblastosis virus oncogene B1, so called C-erb B1/ERBB2/HER-2 gene that acts as a proto-oncogene. It belongs to the HER-2 receptor-family in breast cancer and responds best with anti-Herceptin therapy (anti-tyrosine kinase monoclonal antibody). HER-2 positive breast cancer patient exhibits worse prognosis without Herceptin therapy. Similar incidence and prognosis are reported in other epithelial neoplasms like EGFR + lung non-small cell carcinoma and glioblastoma (grade IV brain glial tumor). Present study highlights the role and connectivity of EGF with various cancers via signaling pathways, cell surface receptors mechanism, macromolecules, mitochondrial genes and neoplasm. Present study describes the EGFR associated gene expression profiling (in breast cancer and NSCLC), relation between mitrochondrial genes and carcinoma, and several in vitro and in vivo models to screen the synergistic effect of various combination treatments. According to this study, although clinical studies including targeted treatments, immunotherapies, radiotherapy, TKi-EGFR combined targeted therapy have been carried out to investigate the synergism of combination therapy; however still there is a gap to apply the scenarios of experimental and clinical studies for further developments. This review will give an idea about the transition from experimental to most advanced clinical studies with different combination drug strategies to treat cancer.
    Matched MeSH terms: Signal Transduction/genetics
  15. Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis
    Wei LK, Menon S, Griffiths LR, Gan SH
    J Hum Hypertens, 2015 Feb;29(2):99-104.
    PMID: 25055800 DOI: 10.1038/jhh.2014.53
    Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.
    Matched MeSH terms: Signal Transduction/genetics
  16. KSR1 regulates BRCA1 degradation and inhibits breast cancer growth
    Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.
    Oncogene, 2015 Apr 16;34(16):2103-14.
    PMID: 24909178 DOI: 10.1038/onc.2014.129
    Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras-dependent cancers, including pancreatic and lung carcinomas but its role in breast cancer has not been well studied. Here, we demonstrate for the first time it functions as a tumor suppressor in breast cancer in contrast to data in other tumors. Breast cancer patients (n>1000) with high KSR1 showed better disease-free and overall survival, results also supported by Oncomine analyses, microarray data (n=2878) and genomic data from paired tumor and cell-free DNA samples revealing loss of heterozygosity. KSR1 expression is associated with high breast cancer 1, early onset (BRCA1), high BRCA1-associated ring domain 1 (BARD1) and checkpoint kinase 1 (Chk1) levels. Phospho-profiling of major components of the canonical Ras-RAF-mitogen-activated protein kinases pathway showed no significant changes after KSR1 overexpression or silencing. Moreover, KSR1 stably transfected cells formed fewer and smaller size colonies compared to the parental ones, while in vivo mouse model also demonstrated that the growth of xenograft tumors overexpressing KSR1 was inhibited. The tumor suppressive action of KSR1 is BRCA1 dependent shown by 3D-matrigel and soft agar assays. KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination through increasing BARD1 abundance. These data link these proteins in a continuum with clinical relevance and position KSR1 in the major oncoprotein pathways in breast tumorigenesis.
    Matched MeSH terms: Signal Transduction/genetics
  17. Fulltext Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5
    Ibrahim E, Diakonov I, Arunthavarajah D, Swift T, Goodwin M, McIlvride S, et al.
    Sci Rep, 2018 05 08;8(1):7110.
    PMID: 29740092 DOI: 10.1038/s41598-018-25569-4
    Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists. The bile acid-induced cAMP production does not lead to an increase in contraction rate, and seems to be mediated by the RI isoform of adenylate cyclase, unlike adrenaline-dependent release which is mediated by the RII isoform. In contrast, bile acids elicited slowing of neonatal cardiomyocyte contraction indicating that other signalling pathways are involved. The conjugated bile acids were found to be partial agonists of the muscarinic M2, but not sphingosin-1-phosphate-2, receptors, and act partially through the Gi pathway. Furthermore, the contraction slowing effect of unconjugated bile acids may also relate to cytotoxicity at higher concentrations.
    Matched MeSH terms: Signal Transduction/genetics
  18. Fulltext A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas
    Ponnampalam SN, Kamaluddin NR, Zakaria Z, Matheneswaran V, Ganesan D, Haspani MS, et al.
    Oncol Rep, 2017 Jan;37(1):10-22.
    PMID: 28004117 DOI: 10.3892/or.2016.5285
    The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.
    Matched MeSH terms: Signal Transduction/genetics
  19. Fulltext TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets
    Wong KK, Hussain FA
    PLoS One, 2020;15(6):e0233884.
    PMID: 32484822 DOI: 10.1371/journal.pone.0233884
    Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4+; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4+; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p<0.01 and false discovery rate<0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.
    Matched MeSH terms: Signal Transduction/genetics
  20. Insights into the molecular mechanisms and signalling pathways of epithelial to mesenchymal transition (EMT) in colorectal cancer: A systematic review and bioinformatic analysis of gene expression
    Azizan S, Cheng KJ, Mejia Mohamed EH, Ibrahim K, Faruqu FN, Vellasamy KM, et al.
    Gene, 2024 Feb 20;896:148057.
    PMID: 38043836 DOI: 10.1016/j.gene.2023.148057
    Colorectal cancer (CRC) is ranked as the second leading cause of mortality worldwide, mainly due to metastasis. Epithelial to mesenchymal transition (EMT) is a complex cellular process that drives CRC metastasis, regulated by changes in EMT-associated gene expression. However, while numerous genes have been identified as EMT regulators through various in vivo and in vitro studies, little is known about the genes that are differentially expressed in CRC tumour tissue and their signalling pathway in regulating EMT. Using an integration of systematic search and bioinformatic analysis, gene expression profiles of CRC tumour tissues were compared to non-tumour adjacent tissues to identify differentially expressed genes (DEGs), followed by performing systematic review on common identified DEGs. Fifty-eight common DEGs were identified from the analysis of 82 tumour tissue samples obtained from four gene expression datasets (NCBI GEO). These DEGS were then systematically searched for their roles in modulating EMT in CRC based on previously published studies. Following this, 10 common DEGs (CXCL1, CXCL8, MMP1, MMP3, MMP7, TACSTD2, VIP, HPGD, ABCG2, CLCA4) were included in this study and subsequently subjected to further bioinformatic analysis. Their roles and functions in modulating EMT in CRC were discussed in this review. This study enhances our understanding of the molecular mechanisms underlying EMT and uncovers potential candidate genes and pathways that could be targeted in CRC.
    Matched MeSH terms: Signal Transduction/genetics
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links