scholarly journals Prostaglandin E2 Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population

2020 ◽  
Vol 21 (20) ◽  
pp. 7680
Author(s):  
Catarina Lopes ◽  
Carina Pereira ◽  
Mónica Farinha ◽  
Rui Medeiros ◽  
Mário Dinis-Ribeiro
Keyword(s):  
Prostaglandin E2 ◽  
Organic Anion ◽  
Caucasian Population ◽  
Organic Anion Transporter ◽  
Independent Manner ◽  
Asian Populations ◽  
Anion Transporter ◽  
Transporter Family ◽  
Ffpe Samples ◽  
Formalin Fixed Paraffin Embedded

Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E2, a key player in the hallmarks of cancer, are mainly regulated by prostaglandin-endoperoxide synthase 2 (PTGS2) and ATP-binding cassette subfamily C member 4 (ABCC4), involved in its synthesis and exportation, respectively, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), responsible for its inactivation. Even though there are distinct molecular signatures across ethnic populations, most published studies focus on Asian populations. Our main aim was to explore the genetic expression of the aforementioned molecules in a Caucasian population. 94 “Normal” and 89 tumoral formalin-fixed paraffin-embedded (FFPE) samples from GC patients were used to assess the mRNA expression of PTGS2, ABCC4, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), SLCO2A1 by Real-Time PCR. We found an upregulation for the PTGS2 gene mean factor of 2.51 and a downregulation for the HPGD and SLCO2A1 genes (mean factor of 0.10 and 0.37, respectively) in tumorous mucosa in a gender-independent manner. In females, we observed an ABCC4 downregulation and a PTGS2 mRNA upregulation compared to males in tumoral mucosa (mean factor of 0.61 and 1.64, respectively). We reported dysregulation of the inflammation triggered PGE2 pathway in a Caucasian population with an intermediate risk for GC, which might highlight the applicability of aspirin in the treatment of GC patients.

scholarly journals Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country

2021 ◽  
Vol 22 (2) ◽  
pp. 648
Author(s):  
Catarina Lopes ◽  
Carina Pereira ◽  
Mónica Farinha ◽  
Rui Medeiros ◽  
Mário Dinis-Ribeiro
Keyword(s):  
Gastric Cancer ◽  
Prostaglandin E2 ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Intermediate Risk ◽  
Multifactor Dimensionality Reduction Analysis ◽  
Allelic Discrimination ◽  
Anion Transporter ◽  
Transporter Family ◽  
Increased Risk

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 (PTGS2), ATP binding cassette subfamily C member 4 (ABCC4), hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), and solute carrier organic anion transporter family member 2A1 (SLCO2A1) PGE2 pathway-related genes with gastric cancer (GC) risk in a European Caucasian population. A hospital-based case-control study gathering 260 GC cases and 476 cancer-free controls was implemented. Using a tagSNP approach, 51 single nucleotide polymorphisms (SNPs) were genotyped through MassARRAY® iPLEX Gold Technology or allelic discrimination by real-time polymerase chain reaction (PCR). Homozygous carriers of the minor allele for both rs689466 and rs10935090 SNPs were associated with a 2.98 and 4.30-fold increased risk for GC, respectively (95% confidence interval (CI): 1.14–7.74, p = 0.027; 95% CI: 1.22–15.16, p = 0.026), with the latter also being associated with an anticipated diagnosis age. A multifactor dimensionality reduction analysis identified an overall three-factor best interactive model composed of age, rs689466, and rs1678374 that was associated with a 17.6-fold GC increased risk (95% CI: 11.67–26.48, p < 0.0001, (cross-validation) CV consistency of 8/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE2 pathway-related genes were identified as risk biomarkers for GC development. This approach may help to identify higher-risk individuals and may contribute to the tailoring screening of GC in intermediate-risk European countries.

scholarly journals SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qing Li ◽  
Dachuan Zhang ◽  
Hui Wang ◽  
Jun Xie ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Gastric Cancer Cells ◽  
Anion Transporter ◽  
Transporter Family ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

Case of pachydermoperiostosis with solute carrier organic anion transporter family, member 2A1 (SLCO2A1) mutations

2015 ◽  
Vol 42 (9) ◽  
pp. 908-910 ◽  
Author(s):  
Satoko Minakawa ◽  
Takahide Kaneko ◽  
Hironori Niizeki ◽  
Hiroki Mizukami ◽  
Yoko Saito ◽  
...  
Keyword(s):  
Family Member ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Transporter Family ◽  
Solute Carrier

scholarly journals cDNA cloning of rat kidney organic anion transporter family.

1996 ◽  
Vol 71 ◽  
pp. 291
Author(s):  
Takashi Sekine ◽  
Makoto Hosoyamada ◽  
Yoshikatsu Kanai ◽  
Hitoshi Endou
Keyword(s):  
Cdna Cloning ◽  
Rat Kidney ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Transporter Family

The organic anion transporter family: from physiology to ontogeny and the clinic

2001 ◽  
Vol 281 (2) ◽  
pp. F197-F205 ◽  
Author(s):  
Douglas H. Sweet ◽  
Kevin T. Bush ◽  
Sanjay K. Nigam
Keyword(s):  
Kidney Development ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
New Drugs ◽  
Spatiotemporal Pattern ◽  
Nucleotide Polymorphisms ◽  
Anion Transporter ◽  
Transporter Family ◽  
Computer Based ◽  
Anionic Drugs

The organic anion transporter (OAT) family handles a wide variety of clinically important compounds (antibiotics, nonsteriodal anti-inflammatory drugs, etc.) and toxins. However, little is known about their appearance during development despite documented differences in the handling of anionic drugs among neonates, children, and adults. A similar spatiotemporal pattern of mRNA expression of the OATs (OAT1–4) during kidney development suggests that OAT genes may be useful in understanding the mechanisms of proximal tubule maturation. Moreover, OAT expression in unexpected extrarenal sites (e.g., spinal cord, bone, skin) has also been detected during development, possibly indicating a role for these transporters in the formation or preservation of extrarenal tissues. The cloning of these transporters also paves the way for computer-based modeling of drug-transporter interactions at the molecular level, potentially aiding in the design and assessment of new drugs. Additionally, increased understanding of single nucleotide polymorphisms in OATs and other transporters may eventually allow the use of a patient's expression profile and polymorphisms to individualize drug therapy.

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