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Functional Investigation of NDRG2 in Pancreatic Islet

Author: LiuXueWu
Tutor: LiuXinPing
School: Fourth Military Medical University
Course: Biochemistry and Molecular Biology
Keywords: NDRG2 Miz1 Comparative genomics Insulin RNA interference Doxorubicin
CLC: Q3
Type: Master's thesis
Year: 2008
Downloads: 38
Quote: 0
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Abstract


Human NDRG2 gene cloning and by the research group first reported (GenBank accession number: AF 159092). It is located on chromosome 14q11.2, encodes a protein with 357 amino acid residues, the molecular weight of approximately 41 kDa protein. In tissue distribution studies Ndrg2, we found that the pancreas immunohistochemistry, Ndrg2 specific expression in islets. Because the islets approximately 60% -80% of the cells are B cells, this finding suggests that specific expression in islets and islet Ndrg2 may be closely related to the function of B cells. Since islet B cell's main function is to secrete insulin, therefore, our goal is to ascertain whether the expression Ndrg2 influence B cells to secrete insulin. In order to ascertain the function of NDRG2 may have, we first used comparative genomics approach to NDRG2 analyzed. In the analysis, we found that islet-specific transcription factor INSM1 and PAX6 may regulate the expression of NDRG2. This may be specifically expressed in islet NDRG2 which are closely related. In addition, NDRG2 in Drosophila homolog of MESK2, this protein can inhibit HNT proteins play a role, because HNT homologous proteins RREB1, which can enhance the positive transcriptional regulatory factor Beta2/NeuroD1 insulin regulation. Thus we can speculate NDRG2 negative regulation of insulin gene transcription. In order to clarify whether Ndrg2 can regulate insulin gene transcription, we have, with sugar and fatty acids stimulate? TC3 cells and then examined the level of insulin secretion and Ndrg2 link between the expression levels. Results We found that in Ndrg2 mRNA expression increased, decreased insulin mRNA expression. While overexpression Ndrg2, the insulin secretion is reduced. This suggests that, Ndrg2 expression and secretion of insulin is inversely related. But whether the mechanism of this process mentioned above, need further study and clarification. We have also observed the overall level of animal Ndrg2 link between insulin secretion. We conducted experiments in mice oral glucose, plasma charged at different time points, with insulin levels were measured by radioimmunoassay, and then take the mouse pancreas, do immunohistochemistry, the expression changes observed Ndrg2. However, we did not observe Ndrg2 and insulin obvious correlation. Furthermore, in order to study the biological function of Miz1, we have designed and constructed Miz1 interference carrier. We will build a successful siRNA expression vectors were transiently transfected into human cervical cancer cell HeLa, using RT-PCR and Western blot observe its effect on Miz1 expression, cell growth by MTT assay. We found that, for the interference Miz1 Miz1 can inhibit the expression plasmid, as compared with the control group, the transfection pSilencer? 3.1-H1 neo-Miz1 in HeLa cells, adriamycin, its growth was more pronounced inhibition. This shows that the siRNA against Miz1 can specifically inhibit Miz1 in human cervical carcinoma Hela cells and HeLa cells enhanced sensitivity to doxorubicin.

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