MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors by inhibiting the expression of target genes, some of which are either directly or indirectly involved with canonical signaling pathways. The relationship between miRNAs and signaling pathways in gastric cancer is extremely complicated. In this paper, we determined the pathogenic mechanism of gastric cancer related to miRNA expression based on recent high-quality studies and then clarified the regulation network of miRNA expression and the correlated functions of these miRNAs during the progression of gastric cancer. We try to illustrate the correlation between the expression of miRNAs and outcomes of patients with gastric cancer. Understanding this will allow us to take a big step forward in the treatment of gastric cancer.

This study aims to investigate the effect and mechanism of Vav3 on the multidrug resistance of gastric cancer. Fluorescence quantitative RT-PCR and western blot assay were used to detect Vav3 and drug resistance genes in gastric cancer tissues as well as gastric cell lines such as SGC7901, SGC7901/adriamycin (ADR) and GES-1. Besides, Vav3-specific small interfering RNA (Vav3-siRNA) was applied to inhibit Vav3 in SGC7901/ADR, and SRB assay was used to determine chemosensitivity. After that, drug resistance genes and proteins in MAPK and PI3K/AKT signaling pathway were detected after Vav3-siRNA transfection. The results showed that overexpressed Vav3 was found in gastric cancer tissues and SGC7901 and SGC7901/ADR cells. Activity of SGC7901/ADR cells transfected with Vav3-siRNA combined with 5-fluorouracil/oxaliplatin was much lower than that of control groups, and MDR1/P-gp, GST-π and Bcl-2, Bax genes were significantly downregulated in Vav3-siRNA transfection group. AKT, ERK and p38 total protein and their phosphorylation levels showed no significant change in Vav3-siRNA-transfected SGC7901/ADR cells, whereas the ratio of C-Jun phosphorylation levels to total C-Jun protein was significantly downregulated. The results suggested that Vav3 may play a role in drug resistance of gastric cancer by inhibiting drug resistance genes MDR1/P-gp, GST-π and Bcl-2 through regulating the JNK signaling pathway.

Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.

Extranodal NK/T-cell lymphoma nasal type (ENKTL) is a subtype of T cell lymphoma with poor prognosis. In this study, we designed a new prognostic model specifically for ENKTL to improve the risk stratification. In 29 ENKTL patients, we screened mutations in 9 ENKTL-associated genes using next-generation sequencing (NGS). We have found that mutated KMT2D was associated with the inferior overall survival (OS) and progression free survival (PFS) and KMT2D or TP53 mutations were associated with a higher mortality rate. Moreover, the difference in PFS among different stratifications was not significant using the International Prognostic Index (IPI) alone but was significant after the mutation status of KMT2D and TP53 were incorporated into the IPI model, forming a harmonious risk stratification reflecting the clinical features and genetic information of ENKTL. In summary, we demonstrate that the prognostic value of the IPI system can be enhanced by integrating the status of genetic mutations.

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