Tingsong Yang

MiR-214 regulate gastric cancer cell proliferation, migration and invasion by targeting PTEN

BackgroundMicroRNAs are a class of small non-coding RNAs that play an important role in various human tumor initiation and progression by regulating gene expression negatively. The aim of this study was to investigate the effect of miR-214 on cell proliferation, migration and invasion, as well as the functional connection between miR-214 and PTEN in gastric cancer.MethodsmiR-214 and PTEN expression was determined in gastric cancer and matched normal tissues, and human gastric cancer cell lines by quantitative real-time PCR. The roles of miR-214 in cell proliferation, migration and invasion were analyzed with anti-miR-214 transfected cells. In addition, the regulation of PTEN by miR-214 was evaluated by Western blotting and luciferase reporter assays.ResultsmiR-214 was noted to be highly overexpressed in gastric cancer tissues and cell lines using qRT-PCR. The expression level of miR-214 is significantly associated with clinical progression and poor prognosis according to the analysis of the clinicopathologic data. We also found that the miR-214 levels are inversely correlated with PTEN in tumor tissues. And PTEN expression level is also associated with metastasis and invasion of gastric cancer. In addition, knockdown of miR-214 could significantly inhibit proliferation, migration and invasion of gastric cancer cells. Moreover, we demonstrate that PTEN is regulated negatively by miR-214 through a miR-214 binding site within the 3’-UTR of PTEN at the posttranscriptional level in gastric cancer cells.ConclusionsThese findings indicated that miR-214 regulated the proliferation, migration and invasion by targeting PTEN post-transcriptionally in gastric cancer. It may be a novel potential therapeutic agent for gastric cancer.

MicroRNA-106b in cancer-associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN

It is well established that the interaction between cancer cells and microenvironment has a critical role in tumor development, but the roles of miRNAs in this interaction are rarely known. Here, we have shown that miR‐106b is up‐regulated in cancer associated fibroblasts compared with normal fibroblasts established from patients with gastric cancer, the expression level of miR‐106b is associated with poor prognosis of patients, and CAFs with down‐regulated miR‐106b could significantly inhibit gastric cancer cell migration and invasion by targeting PTEN. Taken together, these data suggest that miR‐106b might be a novel candidate target for the treatment of gastric cancer.

The role of tomato products and lycopene in the prevention of gastric cancer: a meta-analysis of epidemiologic studies.

BACKGROUND Gastric cancer is the second most common cause of death from cancer worldwide. Epidemiologic studies have examined the possible association between tomato products consumption and gastric cancer, but the relationship between tomato products and the risk of gastric cancer is controversial. We performed a meta-analysis of cohort and case-control studies to analyze this association. METHODS We systematically searched MEDLINE and EMBASE and contacted authors to identify potential studies published from January 1966 to June 2012. We pooled the relative risks from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. RESULTS Twenty-one studies were eligible for our inclusion criteria, in a pooled analysis of all studies, consumption of large amounts of tomato products (in a comparison of the highest and lowest consumption groups) reduced the risk for gastric cancer (odds ratio, 0.73; 95% confidence interval, 0.60-0.90). The pooled OR of lycopene consumption and serum lycopene was 0.88 (95% CI=0.67-1.16) and 0.79 (95% CI=0.59-1.07), respectively. CONCLUSIONS Consumption of large amounts of tomato products is associated with a reduced risk of gastric cancer. However, because of potential confounding factors and exposure misclassification, further studies are required to establish these findings.

Intravenous hMSCs Ameliorate Acute Pancreatitis in Mice via Secretion of Tumor Necrosis Factor-α Stimulated Gene/Protein 6

The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas. Interestingly, we found that i.v.-administered hMSCs with knockdown of TSG-6 expression lost most of their anti-inflammatory effects and thus could not significantly ameliorate SAP. As expected, the effects of hMSCs were also duplicated by i.v. infusion of recombinant TSG-6. Furthermore, our results showed that the increase of oxidative stress, activation of the NLRP3 inflammasome and NF-κB signaling in SAP was substantially inhibited following administration of hMSCs or TSG-6, which was dependent on the presence of CD-44 receptors in acinar cells. In conclusion, our study, for the first time, revealed that novel mechanisms are responsible for the immunomodulatory effect of i.v. hMSCs.

Down-regulation of KLF5 in cancer-associated fibroblasts inhibit gastric cancer cells progression by CCL5/CCR5 axis

ABSTRACT It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblasts compared with normal mucosal fibroblasts. Moreover, KLF5 expression in tumor stroma was closely associated with clinicopathological features such as tumor size, invasion depth, cell grade and lymph node metastasis, as well as poor prognosis in patients with gastric cancer. In addition, we further demonstrated that KLF5-regulating CAFs affect gastric cancer cells progression by CCL5 secretion and activation of CCR5. Taken together, we concluded that KLF5 expression in gastric cancer-associated fibroblasts contribute to poor survival and promote cancer cells progression by activation of CCL5/CCR5 axis, which suggesting that KLF5 in CAFs might be considered as a promising target for the treatment of gastric cancer.

JAK2 inhibitor combined with DC-activated AFP-specific T-cells enhances antitumor function in a Fas/FasL signal-independent pathway.

Objective Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated α-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8+ T-cells combined with or without JAK2 inhibitor. Methods Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway. Results We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8+ T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells. Conclusion These results indicate a Fas/FasL-independent pathway for cellular apoptosis in cancer therapies with the treatment of AFP-specific CD8+ T-cells combined with JAK2 inhibitor.

The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer

Cancer-associated fibroblasts (CAFs) are an important cell type present in solid tumor microenvironments, including that of gastric cancer. They play a vital role in the promotion of tumorigenesis, angiogenesis, and cancer progression through paracrine signaling and modulation of the extracellular matrix. However, the exact molecular mechanism underlying the interaction between gastric cancer cells and stromal fibroblasts remains poorly understood. Recent studies have demonstrated that various factors, such as gene and microRNA variations, are involved in this process. This review discusses recent advances in understanding how these factors are regulated in CAFs and how they affect tumor biology, which may improve our understanding of their role in gastric cancer tumorigenesis and progression and provide new promising targets for therapeutic strategies.