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Preliminary Study On The Effect Of MiR - 410 On Glioma And RANK Protein On Osteoclasts

Posted on:2013-04-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H ZhangFull Text:PDF
GTID:1104330422988416Subject:Surgery
Abstract/Summary:PDF Full Text Request
MicroRNAs are a class of small noncoding RNAs that play important roles in avariety of biological processes including development, apoptosis, proliferation, anddifferentiation. It is also known that miRNAs play a role in human cancers where theycan act either as oncogenes or as onco-suppressors. One of such oncogene is thetyrosine kinase receptor for hepatocyte growth factor, encoded by the MET. The METreceptor promotes invasive growth that results from stimulation of cell motility,invasion, and protection from apoptosis. This oncogene is deregulated in manyhuman tumors, including glioma. Using computational and expression analysis, weidentified that the ‘seed sequence’ of miR-410matched the3’ UTR of the METmRNA and the expression of miR-410was inverse associated with MET inhuman glioma tissues. Luciferase and western blot assay certified that miR-410directly targeted MET in glioma cells. While restoring expression of miR-410inglioma cells led to proliferation inhibition and reduced invasive capability.Furthermore, we showed that miR-410played an important role inregulating MET-induced AKT signal transduction in glioma cells. Whiledownregulation of MET by RNAi, we observed that MET knockdown resulted ineffects similar to that with miR-410transfection in glioma cells. In conclusion,our study demonstrates that miR-410directly targeted oncogene MET in glioma,and restoration of miR-410inhibited cell proliferation and invasion. The skull lesions are common in neurosurgery. The occurrence anddevelopment of skull disorders are closely related to bone metabolism.Changesabout the pathophysiology of bone lesions is studied extensively. The role of RANKsignaling pathway in bone metabolism is studied by researchers as a focus in recentyears. Changes are caused by inhibition or activation of the RANK signaling pathwaycan influence the activity of osteoclasts, thereby causing the bone structure andfunction changes. RANK signaling activation can lead to increase osteoclast activityand differentiation ability, and thus lead to improve the active ability of osteoclasts.Thus it is resulted in the occurrence of bone lesions. In order to explore the effect ofthe RANK signaling pathway on osteoclast in vitro, the recombinant RANK proteinfor the first time was used to action on the osteoclasts to study how to influence theosteoclast activity. The above experiments confirmed that with the increase of therecombinant of RANK protein concentration, the activity of osteoclasts wassignificantly inhibited, showing a dose-effect relationship.
Keywords/Search Tags:miR-410, glioma, MET, AKT, tumor suppressorOsteoclasts, RANK
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