Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and tumor progression. However, the biological function of most lncRNAs remains unknown in human gastric cancer. This study here aims to explore the unknown function of lncRNA MAGI2-AS3 in gastric cancer. First, bioinformatics analysis showed that lncRNA MAGI2-AS3 was overexpressed in gastric cancer tissues, and the overexpression of MAGI2-AS3 has been shown to be associated with poor prognosis in all three independent gastric cancer cohorts (The Cancer Genome Atlas stomach cancer [TCGA_STAD], GEO: GSE62254 and GSE15459). The multivariate analysis indicated that lncRNA MAGI2-AS3 was an independent prognostic factor for both overall survival and disease-free survival of gastric cancer patients. Moreover, MAGI2-AS3 was identified to be an epithelial-mesenchymal transition (EMT)-related lncRNA and was highly co-expressed with ZEB1/2 in both gastric cancer tissues and normal stomach tissues. Loss-of-function and gain-of-function studies showed that lncRNA MAGI2-AS3 could positively regulate ZEB1 expression and the process of cell migration and invasion in gastric cancer. Subcellular location assay showed that lncRNA MAGI2-AS3 was mainly located in the cytoplasm of gastric cancer cells. Bioinformatics analysis and functional experiments revealed that lncRNA MAGI2-AS3 was negatively correlated with miR-141/200a expression and negatively regulated miR-141/200a-3p expression in gastric cancer. Therefore, we speculate that lncRNA MAGI2-AS3 promotes tumor progression through sponging miR-141/200a and maintaining overexpression of ZEB1 in gastric cancer. Nevertheless, we identified that BRD4 is a transcriptional regulator of lncRNA MAGI2-AS3 in gastric cancer. Additionally, our findings highlight that lncRNA MAGI2-AS3 is an ideal biomarker and could be a potential therapeutic target for gastric cancer.

LncRNAs play essential roles in tumorigenesis and tumor progression. Pseudogene UBE2CP3 is an antisense intronic lncRNA. However, the biological function of UBE2CP3 in gastric cancer (GC) remains unknown. In this study, we revealed that lncRNA UBE2CP3 was aberrantly upregulated in multiple independent gastric cancer cohorts, and its overexpression was clinically associated with poor prognosis in GC. UBE2CP3 was mainly located in cytoplasm and promoted migratory and invasive capacities of GC cells in vitro and in vivo. Mechanismly, a novel dysregulated ceRNA network UB2CP3/miR-138-5p/ITGA2 was identified in GC by transcriptome sequencing. Furthermore, rescue assay further confirmed that UBE2CP3 mainly promoted GC progression through miR-138-5p/ITGA2 axis. More importantly, our data proved that UBE2CP3/IGFBP7 could form an RNA duplex, thereby directly interacting with the ILF3 protein. In turn, this RNA-RNA interaction between IGFBP7 mRNA and UBE2CP3 mediated by ILF3 protein plays an essential role in protecting the mRNA stability of UBE2CP3. In addition, transcription factor ELF3 was identified to be a direct repressor of lncRNA UBE2CP3 in GC. Taken together, overexpression of UBE2CP3 promotes tumor progression via cascade amplification of ITGA2 upregulation in GC. Our finding has revealed that the dysregulation of UBE2CP3 is probably due to the downregulation of ELF3 and/or the overexpression of IGFBP7 mRNA in GC. Our findings reveal, for the first time, that UBE2CP3 plays crucial a role in GC progression by modulating miR-138-5p/ITGA2 axis, suggesting that UBE2CP3 may serve as a potential therapeutic target in GC.

MicroRNAs (MiRNAs) play critical roles in regulating target gene expression and multiple cellular processes in human cancer malignant progression. However, the function of miR‐194 in gastric cancer (GC) remains unclear and controversial. In this study, we identified a series of miRNAs that can serve as prognostic biomarkers for GC by analysis of miRNA expression using The Cancer Genome Atlas data. Among them, miR‐100, miR‐125b, miR‐199a, and miR‐194 were the four most promising prognostic biomarkers in GC due to their significant associations with various clinical characteristics of patients. miR‐100, miR‐125b, and miR‐199a predicted poor prognosis in GC, while miR‐194 predicted favorable prognosis in GC. We also provide the first comprehensive transcriptome analysis of miR‐194 in GC. Our data suggest that miR‐194 tends to regulate target genes by binding to their 3′ UTRs in a 7‐mer‐A1, 7‐mer‐m8, or 8‐mer manner. KEGG pathway analysis showed that the cell cycle was one of the pathways most affected by miR‐194 in GC. Moreover, CCND1 was shown to be a novel target gene of miR‐194 in GC. Additionally, downregulation of CCND1 by miR‐194 in GC further led to cell growth inhibition and cell cycle arrest. In conclusion, miR‐100, miR‐125b, miR‐199a, and miR‐194 may have potential as prognostic and diagnostic biomarkers for GC. miR‐194 suppresses GC cell growth mainly through targeting CCND1 and induction of cell cycle arrest.

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BackgroundDifferent gastric cancer (GC) subtypes usually possess distinct clinical outcomes. The function of miR-194 in gastric cancer remains unclear and controversial. This study aimed to identify potential microRNAs that differentially expressed in subtypes and to elucidate the molecular mechanisms of miR-194 in GC.MethodsComprehensive miRNA expression analysis was performed using the available miRNA-seq data from TCGA stomach cancer cohort. The preferences of miR-194 in regulating target genes were determined by RNA sequencing studies. The function of miR-194 in GC was explored in GC cell lines by performing qRT-PCR assays, western blot assays, cell proliferation assays, luciferase report assays and flow cytometry assay.ResultsIn this study, we identified a series of miRNAs that can serve as prognostic biomarkers for GC. Among them, miR-100, miR-125b, miR-199a and miR-194 were the 4 most promising prognostic biomarkers in GC due to their significant associations with various clinical characteristics of patients. MiR-100, miR-125b and miR-199a predicted poor prognosis in GC, while miR-194 predicted favorable prognosis in GC. Besides, we provided the first comprehensive transcriptome analysis about miR-194 in GC. The results showed that miR-194 tended to regulated target genes by binding on their 3' untranslated regions in a 7-mer-A1 or 7-mer-m8 or 8-mer manner. The KEGG pathway analysis showed that cell cycle was one of the most affected pathways by miR-194 in GC. Moreover, CCND1 was proved to be a novel target gene of miR-194 in GC. Additionally, the downregulation of CCND1 by miR-194 in GC further led to cell growth inhibition and cell cycle arrest. ConclusionsMiR-100, miR-125b, miR-199a and miR-194 could serve as prognostic and diagnostic biomarkers for GC. MiR-194 might suppress GC cell growth mainly through targeting CCND1 and induction of cell cycle arrest.