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Wang W.,Central South University | Li X.,Central South University | Zhang W.,Central South University | Li W.,Central South University | And 10 more authors.
Cancer Letters | Year: 2014

Oxidored-nitro domain containing protein 1 (NOR1) is a putative tumor suppressor gene. In this study, NOR1 expression was detected in NPC tissues and non-cancerous nasopharyngeal epithelium. The data showed that NOR1 protein was decreased in NPC tissues. Lost expression NOR1 protein was associated with poor overall and event-free survival of NPC patients. Overexpression of NOR1 in NPC cells resulted in a significant morphological change and decreased expression of epithelial-to-mesenchymal transition (EMT) mediators (e.g., slug and vimentin), but induced cytokeratin 13 expression. A nude mouse metastasis assay revealed that overexpression of NOR1 decreased NPC tumor cells metastasis capacity in vivo. Knockdown of NOR1 expression in HeLa cells was sufficient to abrogate epithelial traits and to enhance cell migration and invasion. Concomitant inhibition of slug or vimentin alleviated induction of EMT, migration or invasion by NOR1 siRNA in HeLa cells in vitro. In conclusion, the data from the current study suggest, for the first time, that NOR1 plays an important role in NPC in ex vivo, in vitro, and in vivo. © 2014 Elsevier Ireland Ltd.

Zhou W.,Central South University | Li X.,Central South University | Li X.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer | Liu F.,Central South University | And 4 more authors.
Acta Biochimica et Biophysica Sinica | Year: 2012

MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA and protein synthesis. Aberrant miRNA expression leads to developmental abnormalities and diseases. The miR-135a is considered to be oncogenic; however, the functions and mechanisms of miR-135a in colorectal cancer (CRC) are largely unknown. Thus, we investigated the functions and mechanisms of miR-135a, especially its relationship with the metastasis suppressor 1 (MTSS1) gene in CRC. The expression of miR-135a was determined by real-time polymerase chain reaction, while its effect on cell proliferation, migration, and invasion was determined by MTT, without and with matrigel, respectively. The expression of MTSS1 was detected by western blot analysis. It was found that miR-135a expression was higher in human CRC samples than in non-tumor control tissue. Using SW480 and SW620 CRC cell lines, increased proliferation was observed in response to miR-135a. We also demonstrated that miR-135a promoted mobility and invasion via transwell assay with and without Matrigel, respectively, of CRC cells. In contrast, inhibition of miR-135a reduced their proliferative and invasive capability. MTSS1 was identified as a candidate target gene of miR-135a by luciferase report assay. Western blot analysis showed that the expression of MTSS1 was regulated by miR-135a overexpression and knockdown. Similarly, miR-135a-mediated cell mobility and invasion were reduced after MTSS1 was knocked down by small interfering RNA. These data indicated that miR-135a promotes the growth and invasion of CRC cells, at least partially, through targeting MTSS1. © 2012 The Author.

Liu M.,Zhuzhou Central Hospital | Wang X.,Central South University | Peng Y.,Hunan Provincial Peoples Hospital | Shen S.,Central South University | And 2 more authors.
BMC Molecular Biology | Year: 2014

Background: As a novel candidate metastasis suppressor gene, Nasopharyngeal carcinoma-associated gene 6 (NGX6) is involved in cellular growth, cell cycle progression and tumor angiogenesis. Previous studies have shown that NGX6 gene is down-regulated in colorectal cancer (CRC). However, little is known about its transcriptional regulation.Results: We defined the minimal promoter of NGX6 gene in a 186-bp region (from-86 to +100) through mutation construct methods and luciferase assays. Results from Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) revealed that Early growth response gene 1 (Egr-1) binds to the Sp1/Egr-1 overlapping site of NGX6 minimal promoter. Overexpression of Egr-1 increased the promoter activity and mRNA level of NGX6 gene; while knock-down of endogenous Egr-1 decreased mRNA expression of NGX6 gene.Conclusion: These results demonstrate that Egr-1 regulates NGX6 gene transcription through an overlapping Sp1/Egr-1 binding site as a positive regulator of NGX6 gene. © 2014 Liu et al.; licensee BioMed Central Ltd.

Zhang L.,Central South University | Liu J.,Central South University | Wang X.,Central South University | Li Z.,Central South University | And 6 more authors.
Current Molecular Medicine | Year: 2014

Lung cancer commonly metastasizes to lymph nodes, brain and bones, which is the main cause of death. It is still a challenge to detect molecular biomarkers for early diagnosis and therapeutics of lung cancer. Our previous study found that bone marrow-derived stroma cells (BMSCs) under tumor microenvironment produced nitric oxide (NO), which was induced by inducible nitric oxide synthase (iNOS), and promoted invasion and metastasis of cancer cells by remodeling cytoskeleton. The aim of this study is to elucidate the relationship between the expressions of iNOS, cytoskeleton protein caldesmon, OPN, and clinical parameters especially the metastasis of lung cancer. We found that nitric oxide can remodel cytoskeleton and promoted the mobility of lung cancer cells. The expressions of iNOS, caldesmon, and OPN are closely correlated to metastasis of lung cancer. The intracranial metastatic tissue samples of lung cancer showed significantly higher expression of iNOS, caldesmon and OPN. A flow-cytometry analysis for peripheral blood of lung cancer patients showed increased EPCAM+/OPN+ cells in circulation of patients with bone metastasis compared to that of patients without metastasis, which is indicative of cancer circulating cells. The concentration of serum OPN was also positively related to the bone metastasis of lung cancer. Taken together, these results suggested that iNOS, caldesmon and OPN may work as biomarkers for metastasis of lung cancer. © 2014 Bentham Science Publishers.

Li N.,Central South University | Li N.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer | Tang A.,Central South University | Tang A.,Hunan Key Laboratory of Nonresolving Inflammation and Cancer | And 12 more authors.
Molecular and Cellular Biochemistry | Year: 2013

Recent data strongly suggests the profound role of miRNAs in cancer progression. Here, we showed miR-126 expression was much lower in HCT116, SW620 and HT-29 colon cancer cells with highly metastatic potential and miR-126 downregulation was more frequent in colorectal cancers with metastasis. Restored miR-126 expression inhibited HT-29 cell growth, cell-cycle progression and invasion. Mechanically, microarray results combined with bioinformatic and experimental analysis demonstrated miR-126 exerted cancer suppressor role via inhibiting RhoA/ROCK signaling pathway. These results suggest miR-126 function as a potential tumor suppressor in colon cancer progression and miR-126/RhoA/ROCK may be a novel candidate for developing rational therapeutic strategies. © 2013 Springer Science+Business Media New York.

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