Chemotherapy is the first-tier treatment regime for gastric cancer (GC) patients at advance stages. Mesenchymal stem cell (MSC) cam affect drug-resistance of GC cells in tumor microenvironment, but the detailed mechanism remains poorly understood. Present study aimed to investigate the regulation of MSC-induced long non-coding RNA (lncRNA) in GC. Dysregulated lncRNAs in GC were analyzed based on GEO data. Stemness and drug-resistance of GC cells were detected by sphere formation, colony formation, CCK-8, and flow cytometry analyses. MicroRNA (miRNA)-related pathways were analyzed by online KEGG analysis tool DAVID6.8. Molecular interactions were determined by luciferase reporter assay, pulldown, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and coimmunoprecipitation (CoIP). Results revealed that MSC co-culture improved stemness and drug-resistance of GC cells. LncRNA histocompatibility leukocyte antigen complex P5 (HCP5) was induced in GC cells by MSC co-culture, contributing to stemness and drug-resistance. Mechanistically, HCP5 sequestered miR-3619-5p and upregulated PPARG coactivator 1 alpha (PPARGC1A), increasing transcription complex Peroxisome proliferator activated receptor (PPAR) coactivator-1α (PGC1α)/CEBPB and transcriptionally inducing carnitine palmitoyltransferase 1 (CPT1), which prompted the fatty acid oxidation (FAO) in GC cells. In conclusion, MSC-induced lncRNA HCP5 drove FAO through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of GC, indicating that targeting HCP5 was a novel approach to enhancing the efficacy of chemotherapy in GC.

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Background: Gastric cancer (GC) is a common-sighted cancer which is hard to cure over the world. Substantial researches revealed that long non-coding RNAs (lncRNAs) were fundamental regulators in the process of cancers. Nevertheless, the biological function of LINC00511 and how LINC00511 was involved in the regulatory system in GC remained unclear.Methods: RIP assays and luciferase reporter assays were performed to illustrate combination between LINC00511 and miR-625-5p. Loss-of-function assays were applied for identifying LINC00511 function in GC. Results:In our study, LINC00511 was discovered significantly high in expression in GC tissues and cell lines. Moreover, LINC00511 showed a strong expression in I/II and III/IV stage. Knockdown of LINC00511 could inhibit the cell proliferation while enhanced cell apoptosis rate in GC. We used nuclear-cytoplasmic fractionation to judge the subcellular localization of LINC00511. Furthermore, miR-625-5p was found to have binding sites for LINC00511 and negatively regulated by LINC00511. Overexpression of miR-625-5p repressed the course of GC. And knockdown of miR-625-5p could recover the effects of LINC00511 silence. Besides, NFIX was discovered as a downstream target of miR-625-5p and overexpression of NFIX could offset the influence of LINC00511 silence. The results of vivo studies manifested that down-regulation of LINC00511 could reduce the Ki67 expression and NFIX while lifted the expression of miR-625-5p. Conclusion:Overall, the results from our study demonstrated that LINC00511 could function as a tumor promoter by targeting miR-625-5p NFIX axis, suggesting LINC00511 could be considered as a target for GC treatment.

Background: Circular RNAs (circRNAs) which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process. However, the expression profile and molecular mechanism of circRNA ATXN7 (circATXN7) is still mostly uncertain in gastric cancer (GC). Methods: qRT-PCR analysis was performed to detect the expression of circATXN7, miR-4319 and ENTPD4 in GC tissues and cells. CCK-8, colony formation, EdU, flow cytometry, TUNEL and transwell assays were conducted to assess the effect of circATXN7 or miR-4319 on cell proliferation, apoptosis and invasion. In vivo assays were utilized to further analyze the function of circATXN7 on the tumorigenesis and progression of GC. The interaction between miR-4319 and circATXN7 (or ENTPD4) was verified using luciferase reporter and RNA pull-down assays. Results: The results showed an upregulated circATXN7 expression in GC tissues and cell lines. Besides, silenced circATXN7 hampered the proliferation and invasion as well as promoted the apoptosis in GC cells. Moreover, low expression of miR-4319 was found in GC. It was determined that circATXN7 acted as a sponge for miR-4319 and had a negative association with miR-4319. We also found that miR-4319 upregulation restrained GC cell proliferation and migration whereas enhanced apoptosis. Subsequently, ENTPD4, the target gene of miR-4319, was found overexpressed in GC. Additionally, it was negatively correlated with miR-4319 whereas positively associated with circATXN7. In vivo experiments, circATXN7 silence was confirmed to inhibit GC tumor growth. Conclusions: CircATXN7 promoted GC development through sponging miR-4319 and regulating ENTPD4, which identified circATXN7 as a new biomarker in GC.

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