Virtual Library

Start Your Search

J. An



Author of

  • +

    MINI 34 - RNA and miRNA (ID 162)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
    • +

      MINI34.08 - MiR-33B Inhibit EMT Through Wnt/β-Catenin/ZEB1 Pathway in Lung Adenocarcinoma (ID 236)

      18:30 - 20:00  |  Author(s): J. An

      • Abstract
      • Presentation

      Background:
      Lung adenocarcinoma is one of the main pathological tissue types of lung small cell lung cancer (NSCLC). Tumor metastases are responsible for approximately 90% of lung adenocarcinoma-related death. The epithelial–mesenchymal transition (EMT) is regarded as a critical event during tumor metastasis. From our previous study, we found miR-33b might be involved in the EMT process of lung adenocarcinoma. However, the specific mechanism of miR-33b regulating EMT has not been established.

      Methods:
      Quantitative real time-PCR (qRT-PCR), in situ hybridization and immunohistochemistry were used to investigate expression of miR-33b and ZEB1 in paired lung adenocarcinoma tissues. MiR-33b target gene ZEB1 was investigated using luciferase reporter gene assays. Western blot, qRT-PCR, immunofluorescence were used to compare the expression levels of ZEB1, E-cad, Vim and β-catenin in A549 cells which were transfected miR-33b or miR-NC, anti-miR-33b or anti-miR-NC and in vivo. MTT was used to analysis growth curves of transfected cells with miR-33b or miR-NC, anti-miR-33b or anti-miR-NC, siRNA-NC or siRNA -ZEB1, siRNA-NC or siRNA-β-catenin. The transfected cells were subjected to Transwell migration and invasion assays.

      Results:
      Mean miR-33b levels were significantly lower in lung adenocarcinoma tissues compared with matched non-cancerous tissues (0.024± 0.028 vs 0.063 ± 0.074, P < 0.0001). The level of miR-33b in NSCLC was strongly correlated with lymph node metastasis (P < 0.0001). ZEB1 levels were significantly higher in lung adenocarcinoma tissues compared with matched non-cancerous tissues (0.447± 0.371vs0.084 ± 0.112, P <0.0001). The level of miR-33b in lung adenocarcinoma was negative correlated with ZEB1 (P < 0.0001,r=-0.6077). MiR-33b significantly inhibited EMT in lung adenocarcinoma metastasis in vitro and vivo (P < 0.05).MiR-33b directly targets the ZEB13[']UTR(P < 0.01).β-catenin was down regulation by overexpression of miR-33b (P < 0.01). MiR-33b overexpression and ZEB1 inhibition suppressed lung adenocarcinoma migration and invasion in vitro (P < 0.01).

      Conclusion:
      On the basis of our results, we propose that miR-33b suppress EMT in lung adenocarcinoma through direct targeting of ZEB1 in vitro and in vivo. Moreover, we found that Wnt/β-catenin/ZEB1 pathway regulated by miR-33b might involved in lung adenocarcinoma EMT. These findings provide new insights into the molecular functions of miR-33b as well asthe role of ZEB1 in lung adenocarcinoma metastasis.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.