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Mitochondrial proteomics of nasopharyngeal carcinoma metastasis.

Liu J, Zhan X, Li M, Li G, Zhang P, Xiao Z, Shao M, Peng F, Hu R, Chen Z - BMC Med Genomics (2012)

Bottom Line: The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity.Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential.These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, PR China.

ABSTRACT

Background: Mitochondrial proteomic alterations of nasopharyngeal carcinoma metastasis remain unknown. Our purpose is to screen mitochondrial proteins for the elucidation of the molecular mechanisms of nasopharyngeal carcinoma metastasis and the discovery of metastasis-related biomarkers.

Methods: Mitochondria were isolated from nasopharyngeal carcinoma metastatic (5-8F) and nonmetastatic (6-10B) cell lines, respectively. After characterization of isolated mitochondria, mitochondrial differentially expressed proteins (DEPs) were quantified by two-dimensional difference in-gel electrophoresis (2D-DIGE), and identified by peptide mass fingerprint (PMF) and tandem mass spectrometry (MS/MS). A functional enrichment analysis and a protein-protein interaction sub-network analysis for DEPs were carried out with bioinformatics. Furthermore, siRNAs transient transfections were used to suppress expressions of some up-regulated DEPs in metastatic cells (5-8F), followed by Transwell Migration assay.

Results: Sixteen mitochondrial DEPs including PRDX3 and SOD2 were identified. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity. A protein-protein interaction sub-network of DEPs was generated with literature data. Ten mitochondrial DEPs including PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5, EIF5A, IDH3B, and PSMC4 were rationalized in the tumor-stroma co-evolution model that mitochondrial oxidative stress directly contributes to tumor metastasis.

Conclusions: Sixteen mitochondrial DEPs were identified with mass spectrometry and ten of them were rationalized in the tumor-stroma co-evolution model. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.

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A protein-protein interaction sub-network of differentially expressed mitochondrial proteins between metastatic 5-8F and nonmetastatic 6-10B cells. It contains 193 nodes (red, green and yellow circles) and 252 edges (blue lines). A green circle means a down-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells. A yellow circle means an up-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells.
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Figure 5: A protein-protein interaction sub-network of differentially expressed mitochondrial proteins between metastatic 5-8F and nonmetastatic 6-10B cells. It contains 193 nodes (red, green and yellow circles) and 252 edges (blue lines). A green circle means a down-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells. A yellow circle means an up-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells.

Mentions: After data extraction from HPRD and NCBI databases, a protein-protein interaction sub-network of mitochondrial DEPs was generated. These results only extended one layer connection, contained 193 nodes and 252 edges (Figure5). In this complex sub-network, the colored circles (nodes) represented proteins and the blue full lines (edges) represented protein-protein interactions. The nodes representing 16 DEPs were labeled in yellow (up-regulated) or green (down-regulated). Seven DEPs that interacted more proteins were VDAC1, VDAC2, PRDX3, PRDX6, SOD2, PHB, and PSMC4. These interaction data provided important clues to insight into the molecular mechanisms of NPC metastasis.


Mitochondrial proteomics of nasopharyngeal carcinoma metastasis.

Liu J, Zhan X, Li M, Li G, Zhang P, Xiao Z, Shao M, Peng F, Hu R, Chen Z - BMC Med Genomics (2012)

A protein-protein interaction sub-network of differentially expressed mitochondrial proteins between metastatic 5-8F and nonmetastatic 6-10B cells. It contains 193 nodes (red, green and yellow circles) and 252 edges (blue lines). A green circle means a down-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells. A yellow circle means an up-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539862&req=5

Figure 5: A protein-protein interaction sub-network of differentially expressed mitochondrial proteins between metastatic 5-8F and nonmetastatic 6-10B cells. It contains 193 nodes (red, green and yellow circles) and 252 edges (blue lines). A green circle means a down-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells. A yellow circle means an up-regulated protein in metastatic 5-8F cells relative to nonmetastatic 6-10B cells.
Mentions: After data extraction from HPRD and NCBI databases, a protein-protein interaction sub-network of mitochondrial DEPs was generated. These results only extended one layer connection, contained 193 nodes and 252 edges (Figure5). In this complex sub-network, the colored circles (nodes) represented proteins and the blue full lines (edges) represented protein-protein interactions. The nodes representing 16 DEPs were labeled in yellow (up-regulated) or green (down-regulated). Seven DEPs that interacted more proteins were VDAC1, VDAC2, PRDX3, PRDX6, SOD2, PHB, and PSMC4. These interaction data provided important clues to insight into the molecular mechanisms of NPC metastasis.

Bottom Line: The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity.Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential.These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, PR China.

ABSTRACT

Background: Mitochondrial proteomic alterations of nasopharyngeal carcinoma metastasis remain unknown. Our purpose is to screen mitochondrial proteins for the elucidation of the molecular mechanisms of nasopharyngeal carcinoma metastasis and the discovery of metastasis-related biomarkers.

Methods: Mitochondria were isolated from nasopharyngeal carcinoma metastatic (5-8F) and nonmetastatic (6-10B) cell lines, respectively. After characterization of isolated mitochondria, mitochondrial differentially expressed proteins (DEPs) were quantified by two-dimensional difference in-gel electrophoresis (2D-DIGE), and identified by peptide mass fingerprint (PMF) and tandem mass spectrometry (MS/MS). A functional enrichment analysis and a protein-protein interaction sub-network analysis for DEPs were carried out with bioinformatics. Furthermore, siRNAs transient transfections were used to suppress expressions of some up-regulated DEPs in metastatic cells (5-8F), followed by Transwell Migration assay.

Results: Sixteen mitochondrial DEPs including PRDX3 and SOD2 were identified. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. The functional enrichment analyses of DEPs discovered five significant biological processes including cellular response to reactive oxygen species, hydrogen peroxide metabolic process, regulation of mitochondrial membrane potential, cell redox homeostasis and oxidation reduction, and five significant molecular functions including oxidoreductase activity, caspase inhibitor activity, peroxiredoxin activity, porin activity and antioxidant activity. A protein-protein interaction sub-network of DEPs was generated with literature data. Ten mitochondrial DEPs including PRDX3, PRDX6, SOD2, ECH1, SERPINB5, COX5A, PDIA5, EIF5A, IDH3B, and PSMC4 were rationalized in the tumor-stroma co-evolution model that mitochondrial oxidative stress directly contributes to tumor metastasis.

Conclusions: Sixteen mitochondrial DEPs were identified with mass spectrometry and ten of them were rationalized in the tumor-stroma co-evolution model. Those 5-8F cells with suppression of PRDX3 showed an increased mobility potential. These data suggest that those mitochondrial DEPs are potential biomarkers for NPC metastasis, and their dysregulation would play important roles in mitochondria oxidative stress-mediated NPC metastatic process.

Show MeSH
Related in: MedlinePlus