BackgroundInterleukin-1β (IL-1β) has been implicated in the progression of gastric adenocarcinoma (GA); however, the molecular mechanisms of action of IL-1β in GA are poorly characterized. P38 and JNK are the major MAPK family members that regulate IL-1β signaling pathways. Here, we investigated the role of both p38 and JNK in IL-1β-induced GA cell migration, invasion and metastatic potential.MethodsThe effects of IL-1β-induced p38 and JNK activation in GA cells were determined using in vitro Transwell migration and invasion assays of MKN-45 and AGS cells, or an in vivo metastasis assay in nude mice. The IL-1β-induced p38 signaling pathway was further characterized in GA cells. Activation of the IL-1β/p38 signaling pathway was also assessed in human primary GA tissues by immunohistochemistry.ResultsIL-1β-induced activation of p38 increased GA cell migration and invasion in vitro and promoted the metastatic potential of GA cells in vivo; these effects were attenuated by p38 siRNA or the p38 inhibitor SB202190. MMP2 or MMP9 siRNAs and the MMP2/9 inhibitor BiPS also inhibited IL-1β-induced GA cell migration and invasion in vitro. IL-1β-induced p38 activation significantly increased MMP2 and MMP9 mRNA and protein expression and activity. Luciferase reporter assays demonstrated that the activator protein-1 (AP-1) and the AP-1 binding sites of the MMP9 promoter (−670/MMP9) were activated by IL-1β-induced p38 activation. Phospho-p38 was significantly upregulated in human GA tissues (compared to matched non-neoplastic tissues), and significantly associated with lymph node metastasis, and invasion beyond the serosa. Expression of phospho-p38 significantly correlated with IL-1β, MMP2, MMP9, and c-fos expression in both human GA tissues and GA cell metastases in the lungs of nude mice. IL-1β was also capable of activating JNK in GA cells, but activation of JNK was not associated with GA cell migration and invasion. Therefore, IL-1β-induced the migration and invasion in GA cells were regulated by p38, but not by JNK.ConclusionsIL-1β-induced p38 activation and the IL-1β/p38/AP-1(c-fos)/MMP2 & MMP9 pathway play an important role in metastasis in GA; this pathway may provide a novel therapeutic target for GA.

Circular RNAs (circRNAs) are implicated in a variety of cancers. However, the roles of circRNAs in gastric cancer (GC) remain largely unknown. In the current study, circRNAs expression profiles were screened in GC, using 5 pairs of GC and matched non-GC tissues with circRNA chip. Preliminary results were verified with quantitative PCR (qRT-PCR). Briefly, total of 713 circRNAs were differentially expressed in GC tissues vs. non-GC tissues (fold change ≥ 2.0, p < 0.05): 191 were upregulated, whereas 522 were downregulated in GC tissues. qRT-PCR analysis of randomly selected 7 circRNAs from the 713 circRNAs in 50 paired of GC vs. non-GC control tissues confirmed the microarray data. Gene ontology (GO) and KEGG pathway analyses showed that many circRNAs are implicated in carcinogenesis. Among differentially expressed circRNAs, hsa_circ_0076304, hsa_circ_0035431, and hsa_circ_0076305 had the highest magnitude of change. These results provided a preliminary landscape of circRNAs expression profile in GC.

BackgroundIncreasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play essential roles in the occurrence and development of human cancers, including gastric cancer (GC). However, the functional and clinical significance of lncRNAs are still poorly understood.MethodsIn this study, the expression of LncRNA HNF1A antisense RNA 1 (HNF1A-AS1) was first examined by lncRNAs microarray analysis in 6 GC tissues, and was then further verified by real-time quantitative reverse transcription PCR (qRT-PCR) both in 3 GC cell lines and 161 cases of GC tissues. We also evaluated the association between HNF1A-AS1 expression and clinicopathological features of patients with GC.ResultsLncRNAs microarray analysis results exhibited that HNF1A-AS1 was downregulated in GCs tissues (mean fold change 2.06, p < 0.05), which was further confirmed by qRT-PCR. The results from qRT-PCR showed that the expression of HNF1A-AS1 was not only downregulated in three GC cell lines (AGS, BGC-823, and MKN-45) relative to that in a normal gastric mucosal epithelial cell line (GES-1), but also decreased in GC tissues relative to that in paired adjacent non-neoplastic tissues (low expression, 94 of 161; low expression rate, 58.38 %). Furthermore, low HNF1A-AS1 expression was associated with tumor size/diameter (p = 0.005, multivariate analysis), levels of serum carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), and RRM1 expression in tissue samples (p = 0.028, p = 0.009, and p = 0.006, respectively).ConclusionsTaken together, our data indicate that lncRNA HNF1A-AS1 may be a regulator of GC, and thus, it may have potential as a novel biomarker and treatment target for this type of cancer.

This study aims to examine the correlation between two single nucleotide polymorphisms (SNPs) of apoptosis-related genes and clinical outcomes in gastric cancer. A total of 221 patients with stage T2 and T3 gastric cancer treated with postoperative chemotherapy between 2003 and 2008 were retrospectively collected in this study to explore the association of rs4645878 located in BAX gene and rs1801270 located in CDKN1A gene with survival, recurrence, and toxicity to chemotherapy. Additionally, immunohistochemistry was used to detect the BAX expression in gastric cancer tissues. Patients carrying at least one variant genotype in BAX SNP (rs4645878) showed a significantly increased recurrence risk [hazard ratio (HR) 2.63; 95 % confidence internal (95 % CI) 1.71-4.03] and poor survival (HR 2.89; 95 % CI 1.88-4.44). Moreover, the recurrence and survival rate in patients with GA genotype was 72.7 and 24.7 %, respectively, compared with total recurrence rate of 54.8 %, P = 0.006, and compared with total survival rate of 46.6 %, P = 0.001. In addition, the GA genotype was related to lower BAX expression in gastric cancer tissues. The CDKN1A (rs1801270) mutant genotype was associated with a significantly decreased risk of hematologic toxicity [odds ratio (OR) 0.28; 95 % CI 0.12-0.63]. SNPs located in BAX and CDKN1A genes are closely associated with clinical outcomes in patients with gastric cancer.