Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma
| العنوان: | Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma |
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| المؤلفون: | Aiping Tong, Canhua Huang, Dequan Zeng, Lijuan Chen, Fenglian Ren, Xiancheng Chen, Yunlong Lei, Yong Zhao, Yuquan Wei, Haiyuan Zhang, Hong Wu, Rui Liu |
| المصدر: | Molecular Cancer, Vol 9, Iss 1, p 81 (2010) Molecular Cancer |
| بيانات النشر: | BMC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Proteomics, Cancer Research, Carcinoma, Hepatocellular, Quantitative proteomics, Blotting, Western, Mice, Nude, Cell Separation, Biology, lcsh:RC254-282, Mice, Phosphoglycerate Mutase 1, Stable isotope labeling by amino acids in cell culture, Carcinoma, medicine, Biomarkers, Tumor, In Situ Nick-End Labeling, Animals, Humans, Neoplasm Staging, Phosphoglycerate Mutase, Cell growth, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Research, Liver Neoplasms, Middle Aged, medicine.disease, Flow Cytometry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Molecular biology, Immunohistochemistry, Xenograft Model Antitumor Assays, Oncology, Hepatocellular carcinoma, Molecular Medicine, Female, Liver cancer |
| الوصف: | BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. There is an urgent need to develop novel biomarkers for early diagnosis, as well as to identify new drug targets for therapeutic interventions.Patients and methods54 paired HCC samples and 21 normal liver tissues were obtained from West China Hospital of Sichuan University. Informed consent was obtained from all the patients or their relatives prior to analysis, and the project was approved by the Institutional Ethics Committee of Sichuan University. Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC)-based proteomics was employed to profile the differentially expressed proteins between a HepG2 human hepatoma cell line and an immortal hepatic cell line L02. Validation of PGAM1 expression was performed by semi-quantitative RT-PCR, immunoblot and immunohistochemistry using clinical samples. shRNA expressing plasmids specifically targeting PGAM1 were designed and constructed by GenePharma Corporation (Shanghai, China), and were utilized to silence expression of PGAM1in vitroandin vivo. Cell proliferation was measured by a combination of colony formation assay and Ki67 staining. Apoptosis was examined by flow cytometry and TUNEL assay.ResultsA total of 63 dysregulated proteins were identified, including 51 up-regulated proteins, and 12 down-regulated proteins (over 2-fold,p< 0.01). Phosphoglycerate mutase 1 (PGAM1) was found markedly upregulated. Clinico-pathological analysis indicated that overexpression of PGAM1 was associated with 66.7% HCC, and strongly correlated with poor differentiation and decreased survival rates (p< 0.01). shRNAs-mediated repression of PGAM1 expression resulted in significant inhibition in liver cancer cell growth bothin vitroandin vivo.ConclusionOur studies suggested that PGAM1 plays an important role in hepatocarcinogenesis, and should be a potential diagnostic biomarker, as well as an attractive therapeutic target for hepatocellular carcinoma. |
| اللغة: | English |
| تدمد: | 1476-4598 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bac307117598c07ea1e88634e5414832Test http://www.molecular-cancer.com/content/9/1/81Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bac307117598c07ea1e88634e5414832 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764598 |
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