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Article ; Online: Myo-Inositol Moderates Glucose-Induced Effects on Human Placental

Watkins, Oliver C / Cracknell-Hazra, Victoria K B / Pillai, Reshma Appukuttan / Selvam, Preben / Yong, Hannah E J / Sharma, Neha / Patmanathan, Sathya Narayanan / Cazenave-Gassiot, Amaury / Bendt, Anne K / Godfrey, Keith M / Lewis, Rohan M / Wenk, Markus R / Chan, Shiao-Yng

Nutrients

2022 Volume 14, Issue 19

Abstract: Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol ...

Abstract	Maternal hyperglycemia is associated with disrupted transplacental arachidonic acid (AA) supply and eicosanoid synthesis, which contribute to adverse pregnancy outcomes. Since placental inositol is lowered with increasing glycemia, and since myo-inositol appears a promising intervention for gestational diabetes, we hypothesized that myo-inositol might rectify glucose-induced perturbations in placental AA metabolism. Term placental explants (
MeSH term(s)	Arachidonic Acid/pharmacology ; Diabetes, Gestational/chemically induced ; Ethanolamines ; Female ; Glucose/pharmacology ; Humans ; Inositol/adverse effects ; Phospholipids ; Placenta/metabolism ; Pregnancy ; Pregnancy Outcome
Chemical Substances	Ethanolamines ; Phospholipids ; Arachidonic Acid (27YG812J1I) ; Inositol (4L6452S749) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-09-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14193988
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Article ; Online: Mechanisms of sphingosine 1-phosphate receptor signalling in cancer.

Patmanathan, Sathya Narayanan / Wang, Wei / Yap, Lee Fah / Herr, Deron R / Paterson, Ian C

Cellular signalling

2017 Volume 34, Page(s) 66–75

Abstract: S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as ... ...

Abstract	S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2017.03.002
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Zs.A 2579: Show issues

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Article ; Online: CRISPR/Cas9 in Stem Cell Research: Current Application and Future Perspective.

Patmanathan, Sathya Narayanan / Gnanasegaran, Nareshwaran / Lim, Moon Nian / Husaini, Roslina / Fakiruddin, Kamal Shaik / Zakaria, Zubaidah

Current stem cell research & therapy

2018 Volume 13, Issue 8, Page(s) 632–644

Abstract: The clustered regularly interspaced short palindromic repeats-associated protein 9 or CRISPR/Cas9 system is one of the hottest topics discussed lately due to its robustness and effectiveness in genome editing. The technology has been widely used in life ... ...

Abstract	The clustered regularly interspaced short palindromic repeats-associated protein 9 or CRISPR/Cas9 system is one of the hottest topics discussed lately due to its robustness and effectiveness in genome editing. The technology has been widely used in life science research including microbial, plant, animal, and human cell studies. Combined with the pluripotency of stem cells, the technology represents a powerful tool to generate various cell types for disease modeling, drug screening, toxicology, and targeted therapies. Generally, the CRISPR/Cas9 system has been applied in genetic modification of pluripotent or multipotent stem cells, after which the cells are differentiated into specific cell types and used for functional analysis or even clinical transplantation. Recent advancement in CRISPR/Cas9 technology has widened the scope of stem cell research and its therapeutic application. This review provides an overview of the current application and the prospect of CRISPR/Cas9 technology, particularly in stem cell research and therapy.
MeSH term(s)	Animals ; CRISPR-Associated Protein 9/metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Genetic Therapy ; Humans ; Regenerative Medicine ; Stem Cell Research ; Stem Cells/metabolism
Chemical Substances	CRISPR-Associated Protein 9 (EC 3.1.-)
Language	English
Publishing date	2018-06-11
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2251937-3
ISSN	2212-3946 ; 1574-888X
ISSN (online)	2212-3946
ISSN	1574-888X
DOI	10.2174/1574888X13666180613081443
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Article ; Online: A PDZ Protein GIPC3 Positively Modulates Hedgehog Signaling and Melanoma Growth.

Patmanathan, Sathya Narayanan / Tong, Bing Teck / Teo, Jia Hao Jackie / Ting, Yong Zheng Jonathan / Tan, Nguan Soon / Sim, Siew Hoon Kenice / Ta, Yng-Cun / Woo, Wei-Meng

The Journal of investigative dermatology

2021 Volume 142, Issue 1, Page(s) 179–188.e4

Abstract: The hedgehog (Hh) pathway is essential for animal development, but aberrant activation promotes cancer growth. In this study, we show that GIPC3, a PDZ domain-containing protein with putative adaptor protein function, positively modulates Hh target gene ... ...

Abstract	The hedgehog (Hh) pathway is essential for animal development, but aberrant activation promotes cancer growth. In this study, we show that GIPC3, a PDZ domain-containing protein with putative adaptor protein function, positively modulates Hh target gene expression in normal fibroblasts and melanoma cells and supports melanoma tumor growth. Using overexpression and epistasis studies, we show that Gipc3 potentiates Hh transcriptional output and that it modulates GLI-dependent transcription independently of Sufu. Whereas we find that GIPC3 protein does not interact with Hh pathway components, Ingenuity Pathway Analyses of GIPC3-interacting proteins identified by coimmunoprecipitation and mass spectrometry show an association with cancer pathogenesis. Subsequent interrogation of The Cancer Genome Atlas and the Human Protein Atlas databases reveals GIPC3 upregulation in many cancers. Using expression screens in selected groups of GIPC3-upregulated cancers with reported Hh pathway activation, we find a significant positive correlation of GIPC3 expression with Hh pathway components GLI1, GLI2, and GPR161 in melanoma lines. Consistently, GIPC3 knockdown in melanoma lines significantly reduces GLI1 and GLI2 expression, cell viability, colony formation, and allograft tumor growth. Our findings highlight previously unidentified roles of GIPC3 in potentiating Hh response and melanoma tumorigenesis and suggest that GIPC3 modulation on Hh signaling may be targeted to reduce melanoma growth.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Allografts ; Animals ; Carcinogenesis ; Cell Growth Processes ; Gene Expression Regulation, Neoplastic ; Hedgehogs/metabolism ; Melanoma/metabolism ; Melanoma, Experimental ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Skin Neoplasms/metabolism ; Zinc Finger Protein GLI1/genetics ; Zinc Finger Protein GLI1/metabolism ; Zinc Finger Protein Gli2/genetics ; Zinc Finger Protein Gli2/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; GPR161 protein, mouse ; Gipc3 protein, mouse ; Receptors, G-Protein-Coupled ; Zinc Finger Protein GLI1 ; Zinc Finger Protein Gli2
Language	English
Publishing date	2021-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2021.04.033
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Article ; Online: The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod.

Patmanathan, Sathya Narayanan / Yap, Lee Fah / Murray, Paul G / Paterson, Ian C

Journal of cellular and molecular medicine

2015 Volume 19, Issue 10, Page(s) 2329–2340

Abstract: Almost all drugs approved for use in humans possess potentially beneficial 'off-target' effects in addition to their principal activity. In some cases this has allowed for the relatively rapid repurposing of drugs for other indications. In this review we ...

Abstract	Almost all drugs approved for use in humans possess potentially beneficial 'off-target' effects in addition to their principal activity. In some cases this has allowed for the relatively rapid repurposing of drugs for other indications. In this review we focus on the potential for re-purposing FTY720 (also known as fingolimod, Gilenya(™)), an immunomodulatory drug recently approved for the treatment of multiple sclerosis (MS). The therapeutic benefit of FTY720 in MS is largely attributed to the immunosuppressive effects that result from its modulation of sphingosine 1-phosphate receptor signalling. However, this drug has also been shown to inhibit other cancer-associated signal transduction pathways in part because of its structural similarity to sphingosine, and consequently shows efficacy as an anti-cancer agent both in vitro and in vivo. Here, we review the effects of FTY720 on signal transduction pathways and cancer-related cellular processes, and discuss its potential use as an anti-cancer drug.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Drug Delivery Systems ; Drug Repositioning ; Fingolimod Hydrochloride/pharmacology ; Humans ; Phenotype ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; Fingolimod Hydrochloride (G926EC510T)
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.12635
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Article ; Online: HOPX functions as a tumour suppressor in head and neck cancer.

Yap, Lee Fah / Lai, Sook Ling / Patmanathan, Sathya Narayanan / Gokulan, Ravindran / Robinson, C Max / White, Joe B / Chai, San Jiun / Rajadurai, Pathmanathan / Prepageran, Narayanan / Liew, Yew Toong / Lopes, Victor / Wei, Wenbin / Hollows, Robert J / Murray, Paul G / Lambert, Daniel W / Hunter, Keith D / Paterson, Ian C

Scientific reports

2016 Volume 6, Page(s) 38758

Abstract: Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC ... ...

Abstract	Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis.
MeSH term(s)	Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; DNA Damage ; DNA Methylation ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/pathology ; Homeodomain Proteins/genetics ; Homeostasis ; Humans ; Promoter Regions, Genetic ; RNA, Messenger/genetics ; Squamous Cell Carcinoma of Head and Neck ; Transcription, Genetic ; Tumor Suppressor Proteins/genetics
Chemical Substances	HOPX protein, human ; Homeodomain Proteins ; RNA, Messenger ; Tumor Suppressor Proteins
Language	English
Publishing date	2016-12-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep38758
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Article ; Online: Association between inflammatory bowel disease gene 5 (IBD5) and interleukin-23 receptor (IL23R) genetic polymorphisms in Malaysian patients with Crohn's disease.

Chua, Kek Heng / Hilmi, Ida / Lian, Lay Hoong / Patmanathan, Sathya Narayanan / Hoe, See Ziau / Lee, Way Seah / Goh, Khean Lee

Journal of digestive diseases

2012 Volume 13, Issue 9, Page(s) 459–465

Abstract: Objective: This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a_1 (rs11739135), IGR2096a_1 (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) ...

Abstract	Objective: This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a_1 (rs11739135), IGR2096a_1 (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) in the Malaysian population. Methods: Blood samples from 80 CD patients and 100 healthy controls were recruited. Genomic DNA was extracted and analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: The results revealed that there was an increased frequency of IGR2198a_1 C allele (8.8% in CD, 1.5% in controls, P < 0.05, OR 6.30, 95% CI 1.77-22.31) and IGR2096a_1 T allele (6.9% in CD, 1.5% in controls, P < 0.05, OR 4.85, 95% CI 1.33-17.69) in the CD patients as compared to the controls, suggesting the two variants were potential risk factors of CD. Both risk alleles (C and T) were highest in Indians. In contrast, no significant difference was observed for the IL23R gene variant (rs1004819) between these two groups (P = 0.941). All genotypes and alleles of this gene variant were present in equal ratios in the CD and control groups (OR 1.02, 95% CI 0.66-1.57 for T allele and OR 0.98, 95% CI 0.64-1.52 for C allele). Conclusions: There is a strong association between both IBD5 locus variants but not the IL23R gene variant with CD in the Malaysian population. The IBD5 locus variants were highest in Indians, which may explain the increased susceptibility of this particular ethnic group to the disease.
MeSH term(s)	Crohn Disease/genetics ; Genetic Predisposition to Disease ; Humans ; Inflammatory Bowel Diseases/genetics ; Malaysia ; Polymorphism, Single Nucleotide ; Receptors, Interleukin/genetics
Chemical Substances	IL23R protein, human ; Receptors, Interleukin
Language	English
Publishing date	2012-09
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2317117-0
ISSN	1751-2980 ; 1751-2972
ISSN (online)	1751-2980
ISSN	1751-2972
DOI	10.1111/j.1751-2980.2012.00617.x
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Article ; Online: Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

Patmanathan, Sathya Narayanan / Johnson, Steven P / Lai, Sook Ling / Panja Bernam, Suthashini / Lopes, Victor / Wei, Wenbin / Ibrahim, Maha Hafez / Torta, Federico / Narayanaswamy, Pradeep / Wenk, Markus R / Herr, Deron R / Murray, Paul G / Yap, Lee Fah / Paterson, Ian C

Scientific reports

2016 Volume 6, Page(s) 25650

Abstract: 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- ... ...

Abstract	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.
Language	English
Publishing date	2016-05-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep25650
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