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Background: Gastric cancer (GC) is the most common and aggressive cancer of the digestive system and poses a serious threat to human health. Since genes do not work alone, our aim was to elucidate the potential network of mRNAs and noncoding RNAs (ncRNAs) in this study. Methods: Transcriptome data of GC were obtained from TCGA. R and Perl were used to obtain the differentially expressed RNAs and construct a competing endogenous RNA (ceRNA) regulatory network. To investigate the biological functions of differentially expressed RNAs, loss-of-function and gain-of-function experiments were performed. Real-time PCR (RT-qPCR), western blot analysis, dual-luciferase reporter assays and fluorescence in situ hybridization were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). Results: Based on TCGA data and bioinformatics analysis, we identified the LINC00163/miR-183/A-Kinase Anchoring Protein 12 (AKAP12) axis. We observed that AKAP12 was weakly expressed in GC and suppressed invasion and metastasis in GC cells, which could be abolished by miR-183. In addition, LINC00163 can be used as a ceRNA to inhibit the expression of miR-183, thus enhancing the anticancer effect of AKAP12. Conclusion: Our results demonstrated that weak LINC00163 expression in GC can sponge miR-183 to promote AKAP12. We established that the LINC00163/miR-183/AKAP12 axis plays an important role in GC invasion and metastasis and may be a potential biomarker and target for GC treatment. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a common tumor-associated lethal disease, and invasiveness and metastasis are primary challenges in its clinical treatment. Hypoxia microenvironment cannot be ignored in the process of metastasis. Hypoxia inducible factor-1α (HIF-1α) is the core component of the hypoxia signaling pathway. The aim of this study was to identify potential hub genes and signaling pathways associated with HIF-1α. We explored the invasiveness- and metastasis-associated phenotype of GC via bioinformatics analysis and molecular studies. Differentially expressed genes (DEGs) were identified in GC cells and HIF-1α-knockdown GC cells. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were identified via centrality analysis and Molecular Complex Detection (MCODE) module analysis. The findings suggested that prolyl 4-hydroxylase beta polypeptide (P4HB) has strong associations with HIF-1α. Further, we observed that HIF-1α and P4HB were upregulated in SGC-7901 and BGC-823 cells. In addition, inhibition of HIF-1α expression reduced invasion and metastasis in GC cells; this effect was partially reversed by P4HB overexpression. Our results confirm that P4HB plays a significant role in the regulatory network of HIF-1α. Therefore, HIF-1α and P4HB may be considered potential biomarkers of GC. [ABSTRACT FROM AUTHOR]

Aberrantly expressed long non-coding RNAs (lncRNAs) are critical instigators of gastric cancer (GC) progression and metastasis. The ceRNA (competing endogenous RNAs) network is well-known in modulating tumor pathological and physiological processes. This research aims to determine the more effective molecular mechanisms of lncRNA PCGEM1 (prostate cancer gene expression marker 1). Bioinformatics database and Ago2-RIP were performed to predict and verify the potential targets of lncRNA PCGEM1. Both gain- and loss-of-function experiments were carried out to dissect the biological functions of RNAs. Fluorescence in situ hybridization, dual-luciferase reporter assays, western blot, and real-time PCR (RT-PCR) experiments were utilized to determine the pathophysiological pathways of competitive endogenous RNAs (ceRNAs). GC cells expressed high levels of cytoplasmic PCGEM1. Loss-of-function experiments displayed that the silencing of PCGEM1 suppressed metastatic and invasive cell qualities. PCGEM1 was also found to have associations with miR-129-5p. Subsequently, luciferase reporter and RIP experiments, together with RT-PCR, verified that PCGEM1 functioned as a ceRNA of P4HA2 (Prolyl 4-Hydroxylase Subunit Alpha 2) via sponging miR-129-5p to up-regulate P4HA2 expression. Finally, the rescue assays determined that P4HA2 overexpression rescued the inhibited cell invasion and metastasis caused by PCGEM1 down-regulation. These findings found that an over-expression of PCGEM1 in GC acts as a miR-129-5p sponge, leading to higher levels of P4HA2. The PCGEM1/miR-129-5p/P4HA2 axis was confirmed to possess a crucial role in GC metastasis and invasion, suggesting its utility as a potential diagnostic and therapeutic biomarker. [ABSTRACT FROM AUTHOR]