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.

Background:Akt2 is important for cell survival. Results: Akt2 increases cell survival by interacting with GAPDH at Thr-237 and inhibiting GAPDH nuclear translocation in ovarian cancer cells. Akt2 activation in ovarian cancer tissues is associated with decreased GAPDH nuclear localization. Conclusion: Activated Akt2 increases ovarian cancer cell survival via inhibition GAPDH-induced apoptosis. Significance: Reveals a novel prosurvival mechanism of Akt2 in ovarian cancer.

Altered signaling pathways or deregulated transcription factors represent an important category of molecular events leading to aberrant gene regulation in gastric cancer, among which the role of WNT/beta-catenin pathway remains unclear. LRH-1 is a critical transcription factor in controlling cell proliferation via crosstalk with the beta-catenin signaling pathway. In order to gain a knowledge of the expression of hLRH-1v1 and hLRH-1 in gastric cancer, a Q-PCR analysis was carried out. Our results showed that in about 50 and 47.6% of 42 tested patients with gastric cancer, the mRNA expression of hLRH-1v1 and hLRH-1 was significantly upregulated, as compared with self-paired normal control, respectively. Besides, overexpression of hLRH-1 was shown to promote the proliferation of gastric adenocarcinoma cell SGC-7901 via induction of cyclin E1. Taken together, our present study demonstrated for the first time the increased expression of hLRH-1v1 and hLRH-1 in human gastric cancer, an alteration which may implicate in tumorigenesis.

The results indicate a beneficial effect of intracerebral transplantation of MSCs on the functional recovery of rat neonates with HIBI.

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.