Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer

Matula, K M; Collie-Duguid, Elaina Susan Renata; Murray, Graeme I.; Parikh, Khyati; Grabsch, Heike; Tan, Patrick; Lalwani, Salina; Garau, Roberta; Ong, Ariel Yuhan; Bain, Gillian; Smith, Asa-Dahle; Urquhart, Gordon; Bielawski, Jacek; Finnegan, M. Beth; Petty, Russell

doi:10.1186/s12885-015-1718-7

Cited by 39 publications

(35 citation statements)

References 50 publications

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“…Among three, the absolute level of SPHK1 expression was higher than two other mRNAs. In addition, the up‐regulation expression of SPHK1 in human GC has been reported previously , while the mechanism has not yet been fully clarified. Therefore, we chose SPHK1 as the object for follow‐up study.…”

Section: Resultsmentioning

confidence: 93%

Up‐regulation and tumor‐promoting role of SPHK1 were attenuated by miR‐330‐3p in gastric cancer

Wang

Gong

et al. 2018

IUBMB Life

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We intended to clarify the role of sphingosine kinase 1 (SPHK1) in gastric cancer (GC) using both in vitro and in vivo assays. The study was designed to identify novel therapeutic targets for GC treatment. Differential analysis was utilized to dissect two gene expression omnibus series (GSE49515 and GSE79973) microarray data form Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) dataset. MRNA and protein expressions were determined by quantitative polymerase chain reaction and Western blot, respectively. GC cell growth was measured by MTT assays and verified by in vivo analysis. Cell cycle and cell apoptosis were detected via flow cytometer observation. Cell migration and invasion were assessed by wound healing assays and Transwell assays. The targeting relationship between miRNA and SPHK1/S1PR1 was identified via dualluciferase assay. Twenty-four common differentially expressed genes were screened out from two gene expression omnibus series (GSE49515 and GSE79973), among which SPHK1 was chosen for its higher fold change. We found elevated SPHK1 expression in GC tissues and cells, along with an increased concentration of SPHK1-generated sphingosine-1-phosphate (S1P) in both GC serum and tissue. SPHK1 knockdown significantly suppressed cell proliferation, migration, and invasion of MKN1 and KATO3 cells. It also blocked cell cycle and induced apoptosis in MKN1 and KATO3 cells. Silencing of SPHK1 also refrained tumor growth and inhibited S1P level. MiR-330-3p directly targeted SPHK1 and S1PR1. Overexpressed miR-330-3p in MKN1 cells repressed SPHK1 and S1PR1 expressions like their chemical inhibitors-SPHK1 inhibitors (FTY720) and S1PR1 inhibitors (VPC23019), and acted anti-tumor both in vitro and in vivo. Our study provides evidence that SPHK1 was promotive for GC tumor growth and cell biological behaviors, and that miR-330-3p targeted 3 0 -UTR of SPHK1 and inhibited its expression. SPHK1 was expected to become a new molecular marker and miR-330-3p a novel therapeutic target for GC. © 2018 IUBMB Life, 70(11):1164Life, 70(11): -1176Life, 70(11): , 2018

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Section: Resultsmentioning

confidence: 93%

Up‐regulation and tumor‐promoting role of SPHK1 were attenuated by miR‐330‐3p in gastric cancer

Wang

Gong

et al. 2018

IUBMB Life

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“…6C). Sphingolipids have been attributed to, among others, insulin resistance, inflammation, and carcinogenesis (71)(72)(73). Detection of high levels of sphingolipids in the serum of obese animals could indicate the potential for susceptibility to many diseases.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic activation of estrogen receptor α increases mitochondrial function, energy expenditure, and brown adipose tissue

Ponnusamy¹,

Tran

Harvey

et al. 2016

FASEB j.

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Most satiety-inducing obesity therapeutics, despite modest efficacy, have safety concerns that underscore the need for effective peripherally acting drugs. An attractive therapeutic approach for obesity is to optimize/maximize energy expenditure by increasing energy-utilizing thermogenic brown adipose tissue. We used in vivo and in vitro models to determine the role of estrogen receptor β (ER-β) and its ligands on adipose biology. RNA sequencing and metabolomics were used to determine the mechanism of action of ER-β and its ligands. Estrogen receptor β (ER-β) and its selective ligand reprogrammed preadipocytes and precursor stem cells into brown adipose tissue and increased mitochondrial respiration. An ER-β-selective ligand increased markers of tricarboxylic acid-dependent and -independent energy biogenesis and oxygen consumption in mice without a concomitant increase in physical activity or food consumption, all culminating in significantly reduced weight gain and adiposity. The antiobesity effects of ER-β ligand were not observed in ER-β-knockout mice. Serum metabolite profiles of adult lean and juvenile mice were comparable, while that of adult obese mice was distinct, indicating a possible impact of obesity on age-dependent metabolism. This phenotype was partially reversed by ER-β-selective ligand. These data highlight a new role for ER-β in adipose biology and its potential to be a safer alternative peripheral therapeutic target for obesity.-Ponnusamy, S., Tran, Q. T., Harvey, I., Smallwood, H. S., Thiyagarajan, T., Banerjee, S., Johnson, D. L., Dalton, J. T., Sullivan, R. D., Miller, D. D., Bridges, D., Narayanan, R. Pharmacologic activation of estrogen receptor β increases mitochondrial function, energy expenditure, and brown adipose tissue.

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“…Previous study has shown that SGPL1 gene is associated with drug resistance in GC cells. 25 In this study, we found that miR-449a is the potential upstream regulator of SGPL1. Overexpression of miR-449a reduced the activity of luciferase reporter gene containing SGPL1 3 0 UTR region, while the variation of seed area in SGPL1 3 0 UTR could reverse the regulation role of miR-449a.…”

Section: Discussionmentioning

confidence: 82%

Tumor suppressor miR-449a inhibits the development of gastric cancerviadown-regulation of SGPL1

et al. 2018

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MicroRNAs (miRNAs) are small noncoding RNAs that are known to participate in the regulation of many physiological and pathological processes, which can indirectly influence the development of malignant behaviors. Numerous studies have demonstrated that miR-449a plays important roles in human carcinogenesis. However, its precise functional and regulatory roles remain unclear. In this study, we mainly explored the functional role of miR-449a in gastric cancer (GC). The expression levels of miR-449a in 98 cases of GC tissues and cell lines were determined by qRT-PCR. The possible mechanisms of miR-449a in GC cells were explored by fluorescence reporter assay. miR-449a expression was significantly lower in GC tissues compared to matched para-carcinoma tissues and was associated with tumor differentiation.Furthermore, in vitro knockdown of miR-449a by siRNA significantly inhibited MKN-28 cell proliferation, migration and invasion as well as tumorigenesis via inducing G0/G1 arrest of GC cells. In addition, we identified SGPL1 as a target of miR-449a and demonstrated that miR-449a regulated SGPL1 expression via binding its 3 0 -UTR region. The experiments indicated that miR-449a functions as a novel tumor suppressor in GC and its anti-oncogenic activity may involve its inhibition of the target gene SGPL1. These findings suggested that miR-449a may be a promising candidate for the development of antitumor drugs targeting GC.

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Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer

Cited by 39 publications

References 50 publications

Up‐regulation and tumor‐promoting role of SPHK1 were attenuated by miR‐330‐3p in gastric cancer

Up‐regulation and tumor‐promoting role of SPHK1 were attenuated by miR‐330‐3p in gastric cancer

Pharmacologic activation of estrogen receptor α increases mitochondrial function, energy expenditure, and brown adipose tissue

Tumor suppressor miR-449a inhibits the development of gastric cancerviadown-regulation of SGPL1

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