Hepatic stellate cells (HSCs) induce immune privilege and promote hepatocellular carcinoma (HCC) by suppressing the immune system. On the other hand, galectin-1 and miRNA-22 (miR-22) are dysregulated in HCC and serve as prognostic indicators for patients. In this study, therefore, we measured galectin-1 and miR-22 expression in HSCs isolated from HCC tissues (Ca-HSCs), and in normal liver tissues (N-HSCs) as a control. We also investigated the apoptosis rate among T cells and the production of cytokines (IFN-η and IL-10) in HSCs co-cultured with T cells. And we used immunohistochemical staining to tested for correlation between galectin-1 expression, CD3 expression and clinicopathological features in 162 HCC patients. Our results showed that galectin-1 expression was much higher in Ca-HSCs than in N-HSCs. Overexpression of galectin-1 promoted HSC-induced T cell apoptosis and cytokine production (IFN-η and IL-10), while miR-22 expression inhibited it. Galectin-1 expression correlated negatively with miR-22 expression in HSCs. High galectin-1 and low CD3 expression levels were associated with poor prognosis in HCC patients. These results suggest that the immunosuppressive microenvironment promoted by HSC-derived galectin-1 in HCC can be inhibited by miR-22. Galectin-1 and miR-22 could potentially serve as prognostic markers and therapeutic targets in HCC.

MicroRNAs (miRNAs) are increasingly recognized as being involved in pancreatic cancer progression by directly regulating the expression of their targets. In this study, we showed that miR-216b-5p expression was significantly decreased in pancreatic cancer tissues and cell lines. In addition, low miR-216b-5p expression was significantly associated with large tumor size and advanced TNM stage. Meanwhile, both Kaplan-Meier and multivariate survival analysis showed that decreased miR-216b-5p expression was associated with overall survival. miR-216b-5p over-expression repressed pancreatic cancer cell proliferation and induced cell cycle arrest and cell apoptosis in vitro and inhibited tumorigenesis in vivo. The translationally controlled tumor protein (TPT1) was identified as a novel direct target of miR-216b-5p. miR-216b-5p up-regulation suppressed TPT1 expression. Moreover, TPT1 mRNA expression levels were increased in pancreatic cancer tissues, and were inversely correlated with miR-216b-5p expression. TPT1 down-regulation had similar effects as miR-216b-5p up-regulation on pancreatic cancer cell progression. The restoration of TPT1 reversed the effect of miR-216b-5p on pancreatic cancer cell progression. Furthermore, we found that miR-216b-5p up-regulation suppressed Pim-3, Cyclin B1, p-Bad and Bcl-xL protein expression. However, the effect of miR-216b-5p up-regulation was partly reversed by TPT1 up-regulation in vitro. Taken together, our findings suggested that miR-216b-5p functions as a potential tumor suppressor by regulating TPT1 in pancreatic cancer cells, and it may represent a potential therapeutic target for patients with pancreatic cancer.

Pancreatic cancer has a five-year overall survival rate <5%, a situation that has not improved since for 40 years. Diabetes mellitus including type 2 diabetes mellitus (T2D) is a suspected risk factor for the development of pancreatic cancer and nearly 45% of the pancreatic cancer cases are likely to present as new onset diabetes cases; however, the nature of association between T2D and pancreatic cancer is still controversial. In this meta-analysis, we examined the association specifically of T2D with pancreatic cancer and the influence of insulin therapy. PubMed, EMBASE, Scholar, Web of Science and Scopus databases were searched to identify clinical and patient oriented studies that examined the incidence of diabetes in pancreatic cancer patients and vice versa, over the last 10 years. All the authors independently screened the articles, and a collective decision was reached about the studies included in the meta-analysis. Parameters analyzed included, the Incidence of diabetes in pancreatic cancer patients; duration history of T2D in pancreatic cancer patients; influence of insulin therapy in T2D patients on pancreatic cancer incidence. Eleven studies with a total of 14,399 patients, of whom 4,080 were T2D-positive and 9,721 were non-diabetic were included in this meta-analysis. T2D duration history was significantly related to pancreatic cancer incidence and insulin therapy effects. In conclusion, recent-onset T2D is probably a manifestation of pancreatic cancer whereas long-term T2D is likely a risk factor for this cancer. Insulin therapy appears to decrease the incidence of pancreatic cancer.

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