Comparative Proteomic Profiling of the Human Lung Adenocarcinoma Cells (CL 1-0) Expressing miR-372
| Autor: | Juo-Shin Lai, 賴若馨 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 Lung cancer remains the most common and lethal illness with an overall poor prognosis worldwide. Widespread metastasis is a common phenomenon in non-small cell lung cancer (NSCLC). The evidences obtained by Jeremy J. W. Chen et al demonstrate that cancer relapse and survival can be predicted with a five-microRNA (miRNA) signature independent of stage or histology types in NSCLC patients. The miR-372 is one of these five miRNAs which may play significant roles in the metastasis process. The study of miR-372 was firstly reported in 2006 by Voorhoeve et al. The evidences about the involvement of miR-372 in the development of human testicular germ cell tumor were proved. The expression of tumor suppressor Lats2 (Large tumor suppressor homolog 2) was possibly inhibited by miR-372 directly. The down-regulation of Lats2 resulted in tumorigenesis and proliferation. To deeper investigate cellular mechanisms involved in miRNA-372 silencing, comparative proteome analysis of the NSCLC CL 1-0 cells expressing miRNA-372 and CL 1-0 cells expressing vector only were performed using two-dimensional gel electrophoresis (2-DE), two-dimensional Fluorescence difference gel electrophoresis (2-D DIGE) and nanoscale capillary LC/ESI quadrupole-TOF MS. Identified up and down-regulated proteins were further classified by their reported biological functions. The identified proteins include antioxidant enzymes, chaperones and/or chaperone-like proteins, mental ion-binding proteins, proteases, signal transduction proteins, transcription/translation regulator proteins, cytoskeleton proteins, and carbohydrate metabolic proteins. The target prediction programs- CRPD (complex regulation prediction database) was used to identify possible targets of miR-372. The results show that Eukaryotic initiation factor 4A-I, Heat shock protein 90-alpha, and RuvB-like 2 are predicted as targets for miR-372. Other identified proteins-Galectin-1, Alpha-enolase (ENO1), Annexin A2 (ANXA2), and some of cytoskeleton and cell motility regulator proteins such as T-complex protein 1 subunit alpha (TCP-1-α) and Thioredoxin (TRX), were likely involved in invasion and metastasis. The results suggest that comparative proteome analyses might contribute to elucidate the metastasis mechanisms related to miR-372. According to our studies, some of these identified proteins may have value as diagnostic and prognostic biomarkers for NSCLC and for better understanding the correlations of miR-372 and lung cancer. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|