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Ouyang J.,Central South University | Ouyang J.,Key Laboratory of Nonresolving Inflammation and Cancer | Wu M.,Central South University | Wu M.,Key Laboratory of Nonresolving Inflammation and Cancer | And 5 more authors.
Oncology Reports | Year: 2013

Oxidored-nitro domain containing protein 1 (NOR1) is a novel member of the nitroreductase family that was first isolated as a tumor suppressor gene from human nasopharyngeal carcinoma (NPC). However, the role of NOR1 gene dysfunction in human cancers has not been addressed. We analyzed the expression of NOR1 in various human cancer and benign tissue specimens and found significant downregulation in nine types of cancer compared with corresponding non-tumor tissues. The recombinant expression vector pCDNA3.1-myc-his-NOR1 was constructed and transfected into human NPC 6-10B nasopharyngeal cancer and HeLa cervical cancer (CCA) cells. We found that stable NOR1 overexpression resulted in suppression of 6-10B and HeLa cell proliferation and led to S phase cell cycle arrest. In addition, NOR1 upregulation enhanced apoptosis in pCDNA3.1-myc-his-NOR1 stably transfected cells, and it also altered the expression of proteins involved in the mitochondria-dependent apoptotic pathway. Furthermore, we also found that the NOR1 protein is a cytoplasmic protein that is partially localized in the mitochondria and endoplasmic reticulum. Therefore, NOR1 is an important tumor suppressor gene associated with NPC and CCA and may play antitumor roles by inhibiting proliferation, preventing colony formation, and promoting the apoptosis of tumor cells via the mitochondrial-dependent apoptotic pathway. However, the precise mechanism behind the NOR1 antitumor effects needs to be investigated further.

Peng Y.,Hunan Normal University | Peng Y.,Central South University | Li X.,Central South University | Li X.,Key Laboratory of Nonresolving Inflammation and Cancer | And 11 more authors.
Molecular BioSystems | Year: 2012

The initiation, promotion and progression of human cancer are complex, polygenic, multi-factored processes. Through systematic proteomic analysis, different stages of CRC (colorectal cancer) biopsies were examined, and 199 differentially expressed proteins were detected between TNM (the tumor, nodes, and metastasis) stages I-IV and normal tissue (One-Way Analysis of Variance, ANOVA; p ≤ 0.05). Instead of looking for biomarkers to distinguish CRC from normal or identify metastatic tumors, we focused on the variation tendency of CRC carcinogenesis and the dynamic expression patterns of proteins among the different stages. Som (self-organizing map clustering) analysis revealed eight unique expression patterns and that the cancer-related proteins were dynamically expressed, and their expression levels changed continuously throughout tumorigenesis. Molecular evidence emerged much earlier than visible, clinical or histological changes, which shows the potential prospect of building molecular staging. Proteins identified by MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry) were mainly involved in energy metabolism, acetylation and signaling pathways. Validation experiments using immunoblotting and immunohistochemistry (IHC) agreed with the 2D-DIGE (two-dimensional difference in gel electrophoresis) data. After survival classifier and LOOCV (leave-one-out cross-validation) analyses, the new prognostic biomarkers (78 kDa Glucose-Regulated Protein precursor (GRP78), Fructose-bisphosphate Aldolase A (ALDOA), Carbonic Anhydrase I (CA1) and Peptidyl-prolyl cis-trans isomerase A or Cyclophilin A (PPIA)) provided good survival prediction for TNM stage I-IV patients. The new biomarkers derived from the dynamic patterns of these proteins' expression provide is a good supplementary method for determining prognosis for CRC, especially for the TNM stage III and IV patients. © 2012 The Royal Society of Chemistry.

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