Back to Search
Start Over
MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer
- Source :
- Gut
- Publication Year :
- 2020
- Publisher :
- BMJ Publishing Group, 2020.
-
Abstract
- The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM).ObjectiveTo identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM.DesignWe performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4– cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b.ResultsMicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth.ConclusionTaken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.
- Subjects :
- 0301 basic medicine
Myeloid
interferon-alpha
Biology
Helicobacter Infections
Transcriptome
03 medical and health sciences
Mice
0302 clinical medicine
helicobacter felis
Stomach Neoplasms
Metaplasia
microRNA
medicine
Animals
gastric inflammation
Mice, Knockout
Gene knockdown
Helicobacter pylori
Stomach
gastric cancer
Myeloid-Derived Suppressor Cells
Gastroenterology
Cancer
medicine.disease
biology.organism_classification
gastric metaplasia
Gene Expression Regulation, Neoplastic
Disease Models, Animal
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Cell Transformation, Neoplastic
030220 oncology & carcinogenesis
Cancer research
Helicobacter felis
medicine.symptom
Carrier Proteins
Precancerous Conditions
Subjects
Details
- Language :
- English
- ISSN :
- 14683288 and 00175749
- Volume :
- 69
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Gut
- Accession number :
- edsair.doi.dedup.....c0f2ebf6b7ab683a0dcacf112ef01a25