Antitumor Function Of The Truncated Peptides From NDRG2 And The Correlation Between Ndrg2’s Expression And Prognosis Of The Patients With Glioma

The awful prognosis of glioma is serious threaten for people’s heath. It is of a persistent work for all neuroscientists and neurologists to pursue the reliable prognositic biomarker and the new therapies with well-prognosis.Our team members found the human NDRG2 gene first and confirmed its low expression in many tumor tissues and cell lines. It is downstream regulated by MYC, and inhibits the cell proliferation when it is transfected into glioma cell lines and induced to overexpress. Thus the gene is regarded as a candidate for tumor suppressor gene and attracts our attention for a long time.Two questions focus our attention on the present study: Which part of the NDRG2 plays the leading role in its antitumor function? What correlation exists between the expression of NDRG2 and the patients’overall survival?The first part of the present study is about the correlation between the structure of NDRG2 and its antitumor function. Here, we started our research from the analysis for the molecular structure of NDRG2, predicted its 3-dimentional structure according to its homologous protein of mouse. Then, we truncated the NDRG2 protein into several parts theoretically, designed and constructed the eukaryotic expression plasimds for each truncated peptides of NDRG2. Two glioma cell lines (U87MG and U251) and a classical cervical cancer cell line (HeLa) were transfected by the plasmids and their cell cycle arrest and apoptosis were dectected by flowcytometry. More than that, the proliferation of HeLa cells after being transfected by our plasminds was also observed by MTT assay. We found that the C-terminal of NDRG2 plays the leading role in its antitumor fuction, and sometimes the truncated Peptide AC and Peptide C showed more powerful antitumor function than the whole length protein. Peptide AC is the mimic of the big domain of original NDRG2 protein and Peptide C is consisted of 129 amino acids adjacent to C-terminal.In the second part, we studied the expression profile of NDRG2 in human astrocytoma tissues by immunohistochemistry and found it was significantly downregulated in astrocytomas. The level of expression of NDRG2 showed an inverse correlation with the WHO grade of tumors and a positive one with the life span of patients. Our results suggested that NDRG2 may play a pivotal role as a potent tumor suppressor and a prognostic biomarker candidate for human astrocytoma.In brief, we located the part playing the leading role for NDRG2 antitumor function and assessed the value of NDRG2 as prognostic biomarker in the study.