Comparative analysis of sphingomyelin synthase 1 gene expression at the transcriptional and translational levels in human tissues

Sudarkina, Olga Yu.; Filippenkov, Ivan B.; Brodsky, Ilya; Limborska, Svetlana A.; Dergunova, Lyudmila V.

doi:10.1007/s11010-015-2427-x

Cited by 11 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, SMS1 increase due to SMS2 silencing did not significantly increase the expression of the corresponding protein. This behavior has previously been reported for SMS1 [23], reflecting the high post-transcriptional regulation these enzymes undergo. SMS1 is a complex gene with several splicing forms [43] capable of generating circular and linear RNAs [44,45].…”

Section: Discussionsupporting

confidence: 80%

“…However, siRNAs treatments did not result in a strong decrease of SMS protein levels, suggesting that small changes in protein amount were enough to produce these effects, or that the protein present was not fully active. The lack of correlation between mRNA levels (Figure 5F,G) and protein levels (Figure S5) after siRNAs treatment was previously reported for SMS1 [23].…”

Section: Resultssupporting

confidence: 53%

See 1 more Smart Citation

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

Fernández‐García

Rosselló

Rodríguez-Lorca

et al. 2019

Cancers

View full text Add to dashboard Cite

Background: 2-Hydroxyoleic acid (2OHOA) is particularly active against glioblastoma multiforme (GBM) and successfully finished a phase I/IIA trial in patients with glioma and other advanced solid tumors. However, its mechanism of action is not fully known. Methods: The relationship between SMS1 and SMS2 expressions (mRNA) and overall survival in 329 glioma patients was investigated, and so was the correlation between SMS expression and 2OHOA’s efficacy. The opposing role of SMS isoforms in 2OHOA’s mechanism of action and in GBM cell growth, differentiation and death, was studied overexpressing or silencing them in human GBM cells. Results: Patients with high-SMS1 plus low-SMS2 expression had a 5-year survival ~10-fold higher than patients with low-SMS1 plus high-SMS2 expression. SMS1 and SMS2 also had opposing effect on GBM cell survival and 2OHOA’s IC50 correlated with basal SMS1 levels and treatment induced changes in SMS1/SMS2 ratio. SMSs expression disparately affected 2OHOA’s cancer cell proliferation, differentiation, ER-stress and autophagy. Conclusions: SMS1 and SMS2 showed opposite associations with glioma patient survival, glioma cell growth and response to 2OHOA treatment. SMSs signature could constitute a valuable prognostic biomarker, with high SMS1 and low SMS2 being a better disease prognosis. Additionally, low basal SMS1 mRNA levels predict positive response to 2OHOA.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Resultssupporting

confidence: 53%

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

Fernández‐García

Rosselló

Rodríguez-Lorca

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…We established that the transcriptional diversity of the SGMS1 gene is provided by the presence of alternative promoters, alternative polyadenylation and exon splicing. [5][6][7][8][9] In human tissues, transcripts with a 5 0 untranslated region (5 0 UTR) that includes exons 1-6 and exon 7, with a coding region that is localized in exons 7-10 and in a portion of exon 11, and with a 3 0 UTR that stems entirely to the remaining portion of exon 11 are mostly abundant. 8 The multiplicity and complexity of the biological processes that involve the sphingomyelin synthase 1 (SMS1) protein suggest the high specificity of the control of the function of its encoding gene in the individual cells and tissues of organisms.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues

et al. 2015

Self Cite

View full text Add to dashboard Cite

The human sphingomyelin synthase 1 gene (SGMS1) encodes an essential enzyme that is involved in the synthesis of sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. Among the products of SGMS1, we found new transcripts, circular RNAs (circRNAs), that contain sequences of the gene's 5 0 untranslated region (5 0 UTR). Some of them include the gene's coding region and fragments of introns. An analysis of the abundance of circRNAs in human tissues showed that the largest transcripts were predominantly found in different parts of the brain. circRNAs of rat and mouse sphingomyelin synthase 1 orthologous genes were detected and are highly similar to the human SGMS1 gene transcripts. A quantitative analysis of the abundance of such transcripts also revealed their elevated amount in the brain. A computational analysis of sequences of human circRNAs showed their high potential of binding microRNAs (miRNAs), including the miRNAs that form complexes with Ago proteins and the mRNA of SGMS1. We assume that the circRNAs identified here participate in the regulation of the function of the SGMS1 gene in the brain.

show abstract

“…Table 1 summarizes the localization of enzymes that regulate ceramide formation and SphKs in the kidney [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Regarding subcellular localization of enzymes, sphingomyelin synthase (SMS)1/2 is predominantly in the Golgi and to a small extent in the plasma membrane [ 20 ].…”

Section: The Enzymes That Generate Ceramide and S1p In The Kidneymentioning

confidence: 99%

A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury

Ueda

2022

IJMS

View full text Add to dashboard Cite

Reactive oxygen species (ROS) modulate sphingolipid metabolism, including enzymes that generate ceramide and sphingosine-1-phosphate (S1P), and a ROS-antioxidant rheostat determines the metabolism of ceramide-S1P. ROS induce ceramide production by activating ceramide-producing enzymes, leading to apoptosis, while they inhibit S1P production, which promotes survival by suppressing sphingosine kinases (SphKs). A ceramide-S1P rheostat regulates ROS-induced mitochondrial dysfunction, apoptotic/anti-apoptotic Bcl-2 family proteins and signaling pathways, leading to apoptosis, survival, cell proliferation, inflammation and fibrosis in the kidney. Ceramide inhibits the mitochondrial respiration chain and induces ceramide channel formation and the closure of voltage-dependent anion channels, leading to mitochondrial dysfunction, altered Bcl-2 family protein expression, ROS generation and disturbed calcium homeostasis. This activates ceramide-induced signaling pathways, leading to apoptosis. These events are mitigated by S1P/S1P receptors (S1PRs) that restore mitochondrial function and activate signaling pathways. SphK1 promotes survival and cell proliferation and inhibits inflammation, while SphK2 has the opposite effect. However, both SphK1 and SphK2 promote fibrosis. Thus, a ceramide-SphKs/S1P rheostat modulates oxidant-induced kidney injury by affecting mitochondrial function, ROS production, Bcl-2 family proteins, calcium homeostasis and their downstream signaling pathways. This review will summarize the current evidence for a role of interaction between ROS-antioxidants and ceramide-SphKs/S1P and of a ceramide-SphKs/S1P rheostat in the regulation of oxidative stress-mediated kidney diseases.

show abstract

Comparative analysis of sphingomyelin synthase 1 gene expression at the transcriptional and translational levels in human tissues

Cited by 11 publications

References 39 publications

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

The Opposing Contribution of SMS1 and SMS2 to Glioma Progression and Their Value in the Therapeutic Response to 2OHOA

Circular RNA of the human sphingomyelin synthase 1 gene: Multiple splice variants, evolutionary conservatism and expression in different tissues

A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury

Contact Info

Product

Resources

About