Spns1

Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis...

Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2 - a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome. We generated Spns1 knockout cells and mice and employed lipidomic and metabolomic approaches to reveal SPNS1 ligand identity. Global knockout of Spns1 caused embryonic lethality between E12...

Per- and polyfluoroalkyl substances (PFAS) are man-made long-lasting chemical compounds that are found in everyday household items. Today they occur in the environment as a major group of pollutants. These compounds are broadly used in commercial product preparation such as, for food packaging, nonstick coatings, and firefighting foam. In humans, PFAS can cause immune disorders, impaired fetal development, abnormal skeletal tissue development, osteoarthritis, thyroid dysfunctions, cholesterol changes, affect insulin regulation and lipid metabolism, and are also involved in the development of fatty liver disease...

There are 78 loci associated with Parkinson's disease in the most recent genome-wide association study (GWAS), yet the specific genes driving these associations are mostly unknown. Herein, we aimed to nominate the top candidate gene from each Parkinson's disease locus and identify variants and pathways potentially involved in Parkinson's disease. We trained a machine learning model to predict Parkinson's disease-associated genes from GWAS loci using genomic, transcriptomic and epigenomic data from brain tissues and dopaminergic neurons...

Lysosomes degrade macromolecules and recycle their nutrient content to support cell function and survival. However, the machineries involved in lysosomal recycling of many nutrients remain to be discovered, with a notable example being choline, an essential metabolite liberated via lipid degradation. Here, we engineered metabolic dependency on lysosome-derived choline in pancreatic cancer cells to perform an endolysosome-focused CRISPR-Cas9 screen for genes mediating lysosomal choline recycling. We identified the orphan lysosomal transmembrane protein SPNS1 as critical for cell survival under choline limitation...

The lysosome is central to the degradation of proteins, carbohydrates, and lipids and their salvage back to the cytosol for reutilization. Lysosomal transporters for amino acids, sugars, and cholesterol have been identified, and the metabolic fates of these molecules in the cytoplasm have been elucidated. Remarkably, it is not known whether lysosomal salvage exists for glycerophospholipids, the major constituents of cellular membranes. By using a transport assay screen against orphan lysosomal transporters, we identified the major facilitator superfamily protein Spns1 that is ubiquitously expressed in all tissues as a proton-dependent lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) transporter, with LPC and LPE being the lysosomal breakdown products of the most abundant eukaryotic phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively...

Better understanding interactions between SARS-CoV-2 and host cells should help to identify host factors that may be targetable to combat infection and COVID-19 pathology. To this end, we have conducted a genome-wide CRISPR/Cas9-based loss-of-function screen in human lung cancer cells infected with SARS-CoV-2-pseudotyped lentiviruses. Our results recapitulate many findings from previous screens that used full SARS-CoV-2 viruses, but also unveil two novel critical host factors: the lysosomal efflux transporter SPNS1 and the plasma and lysosomal membrane protein PLAC8...

Muscle development and homeostasis are critical for normal muscle function. A key aspect of muscle physiology during development, growth, and homeostasis is modulation of protein turnover, the balance between synthesis and degradation of muscle proteins. Protein degradation depends upon lysosomal pH, generated and maintained by proton pumps. Sphingolipid transporter 1 ( spns1 ), a highly conserved gene encoding a putative late endosome/lysosome carbohydrate/H+ symporter, plays a pivotal role in maintaining optimal lysosomal pH and spns1-/- mutants undergo premature senescence...

Accumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development and metastasis of hepatocellular carcinoma (HCC), but the understanding of their prognostic value is limited. Thereafter, LIMMA and survival analysis were conducted in both ICGC and TCGA databases and a total of 10 hub autophagy-related genes, namely, NPC1, CDKN2A, RPTOR, SPHK1, HGS, BIRC5, SPNS1, BAK1, ATIC, and MAPK3, were collected...

Background: Autophagy regulates many cell functions related to cancer, ranging from cell proliferation and angiogenesis to metabolism. Due to the close relationship between autophagy and tumors, we investigated the predictive value of autophagy-related genes. Methods: Data from patients with hepatocellular carcinoma were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. A regression analysis of differentially expressed genes was performed. Based on a prognostic model, patients were divided into a high-risk or low-risk group...

Spinster homolog 3 (SPNS3) belongs to the Spinster (SPNS) family which participates in sphingolipid transportation through the cell membrane. However, the functions of SPNS3 in acute myeloid leukemia (AML) are unknown. This study obtained SPNS3 from a gene set that was related to AML relapse and evaluate whether high SPNS3 expression induced apoptosis resistance in an AML cell line, which is consistent with the role of SPNS3 as a marker of poor prognosis in the clinic. Moreover, internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutation and the AC127521...

Perfluorooctane sulfonate (PFOS) is one kind of persistent organic pollutants. In previous study, we found that PFOS induced autophagy-dependent lysosomal membrane permeabilization (LMP) in hepatocytes, and siRNA against lysosomal permease spinster 1 (SPNS1) relieved PFOS-induced LMP. However, whether and how SPNS1 functioned as the link between autophagy and LMP was still not defined. In this study, we constructed a stable cell line expressing high levels of SPNS1. We found that SPNS1 interacted specifically with α-tubulin of tyrosinated isotype by pull-down assay...

Carbofuran is a broad-spectrum synthetic pesticide. Its exposure to non-target mammals affects the biological system through the induction of oxidative stress. Since oxidative stress is a major contributing factor to cellular autophagy and senescence, our present investigation determined the impacts of carbofuran-induced oxidative stress on cellular autophagy and senescence. A transmembrane protein, Spinster homolog 1 (Spns1), is involved in autophagic lysosomal metabolism. Its mutation accelerates the cellular senescence and shortens the lifespan...

BACKGROUND: Autophagy is closely related to skin cutaneous melanoma (SKCM), but the mechanism involved is unclear. Therefore, exploration of the role of autophagy-related genes (ARGs) in SKCM is necessary. MATERIALS AND METHODS: Differential expression autophagy-related genes (DEARGs) were first analysed. Univariate and multivariate Cox regression analyses were used to evaluate the expression of DEARGs and prognosis of SKCM. Further, the expression levels of prognosis-related DEARGs were verified by immunohistochemical (IHC) staining...

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects...

Type-2 diabetes and obesity are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches and are among the most frequent and highly complex and heterogeneous in nature. Based on epidemiological evidence, it is known that the patients suffering from obesity are considered to be at a significantly higher risk of type-2 diabetes. There are several pieces of evidence that support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of type-2 diabetes...

Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival...

BACKGROUND: Autophagy is a programmed cell degradation mechanism that has been associated with several physiological and pathophysiological processes, including malignancy. Improper induction of autophagy has been proposed to play a pivotal role in the progression of hepatocellular carcinoma (HCC). METHODS: Univariate Cox regression analysis of overall survival (OS) was performed to identify risk-associated autophagy-related genes (ARGs) in HCC data set from The Cancer Genome Atlas (TCGA)...

Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by proliferation of immature myeloid cells, with impaired differentiation and maturation. Spinster homolog (SPNS) is a widely distributed transmembrane transporter, which assists sphingolipids in playing their roles through the cell membrane. However, the expression and clinical implication of the SPNS family has not been investigated in AML. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and SPNS1-3 expression data were contained in our study...

Lysosomal storage disorders are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. 573C10 is a Schwann cell line derived from a mouse model of Niemann-Pick type C disease-1, NPC (-/-). Under serum-starved conditions, NPC (-/-) cells manifested impaired autophagy accompanied by an increase in the amount of p62 and lysosome enlargement. Addition of L-leucine to serum-starved NPC (-/-) cells ameliorated the enlargement of lysosomes and the p62 accumulation...