More than half of transplanted b -cells undergo apoptotic cell death triggered by nonimmunological factors within a few days after transplantation. To investigate the dynamic hypoxic responses in early transplanted islets, syngeneic islets were transplanted under the kidney capsule of balb/c mice. Hypoxiainducible factor-1a (HIF-1a ) was strongly expressed at post-transplant day (POD) 1, increased on POD 3, and gradually diminished on POD 14. Insulin secretion decreased on POD 3 in association with a significant increase of HIF-1a -related b -cell death, which can be suppressed by short-term hyperbaric oxygen therapy. On POD 7, apoptosis was not further activated by continually produced HIF-1a . In contrast, improvement of nerve growth factor and duodenal homeobox factor-1 (PDx-1) production resulted in islet graft recovery and remodeling. In addition, significant activation of vascular endothelial growth factor in islet grafts on POD 7 correlated with development of massive newly formed microvessels, whose maturation is advanced on POD 14 with gradual diminution of HIF-1a . We conclude that (1) transplanted islets strongly express HIF-1a in association with b -cell death and decreased insulin production until adequate revascularization is established and (2) early suppression of HIF-1a results in less b -cell death thereby minimizing early graft failure.

The above data suggest potential advantages of NGF for islet survival following transplantation. This neurotrophic approach may prove beneficial in human islet transplantation.

MicroRNAs (miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly discuss the potential uses of miRNAs in colorectal cancer (CRC) diagnosis. We also shed light on the important corresponding miRNA targets and on the major regulators of miRNAs. Furthermore, we discuss miRNA activity in assessing the prognosis and recurrence of CRC as well as in modulating responsiveness to chemotherapy. Based on the various pro-oncogenic/anti-oncogenic roles of miRNAs, the advantages of a therapeutic strategy based on the delivery of miRNA mimics are also mentioned. Together, miRNA seems to be an excellent tool for effectively monitoring and targeting CRC.

MicroRNA 130b (miR-130b) is significantly dysregulated in various human tumor types. In this study, using a microarray assay, we characterized the upregulation of miR-130b expression in colorectal cancer (CRC) specimens. However, there is limited knowledge about the roles of aberrant miR-130b expression in CRC. Our studies in CRC cells demonstrated that miR-130b significantly decreases cell migration and invasion, but it has no evidently effects on cell proliferation and apoptosis. In the overexpression miR-130b CRC cells and the CRC specimens, we observed a decreased level of integrin β1 protein, which is considered as a key molecule involved in cell motility. The targeting of the 3′-UTR region of integrin β1 gene by miR-130b was revealed using a luciferase reporter assay. The regulation of integrin β1 by miR-130b was further shown using the miR-130b mimics and the inhibitor of miR-130b. The impaired motility of the miR-130b overexpression cells is recovered partly by the expression of integrin β1 lacking the 3′-UTR. Additionally, the knockdown of integrin β1 also gives rise to a decrease in cell migration and invasion, which is similar to the impeded motility due to overexpression of miR-130b in CRC cells. Furthermore, the inverse expressions of miR-130b and integrin β1 were observed in CRC specimens. In summary, these data demonstrate that miR-130b downregulates its target-integrin β1, leading to the impaired migration and invasion of CRC cells.

No abstract