Wang CY1, Tsai CH2, Chang CY2, Liao MJ2, Liu RS2-4 and Lee YJ2,5*
1Department of Medical Imaging, Cheng Hsin General Hospital, Taiwan
2Departments of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taiwan
3Department of Nuclear Medicine, National PET/Cyclotron Center, Taiwan
4Molecular and Genetic Imaging Core, Medical School, National Yang-Ming University, Taiwan
5Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taiwan
Metastatic lung cancer means the spread of cancer from the primary site to nearby structures or distant organs. Epithelial-mesenchymal transition (EMT) is an important mechanism to be associated with metastasis. Suppression of EMT may prevent the cancer metastasis. We previously found that over-expression of cofilin-1, an actin binding protein belongs to the actin depolymerizing factor (ADF)/cofilin family leads to morphological change and inhibition of invasion of human non-small cells lung cancer (NSCLC). This effect is associated with up-regulation of the tumor suppressive let-7 microRNA through TWIST-1 transcription factor, an important biomarker of EMT. Here we investigated whether other EMT related molecules would be affected by overexpressed cofilin-1. Over-expression of cofilin-1 in human H1299 lung cancer cells also suppressed SNAIL-1 transcription factors, but E-cadherin and N-cadherin were not significantly affected. Importantly, over-expression of cofilin-1 induced let-7 could be suppressed by enforced expression of SNAIL-1, suggesting that EMT related transcription factors can be suppressed by over-expressed cofilin-1 to induce let-7 expression. However, over-expression of cofilin-1 may not suppress EMT. To monitor the effects of cofilin-1 and let-7 on lung cancer migration in vivo, we established a multiple reporter genes transduced lung cancer cell line that can be detected using the reporter gene imaging. The cofilin-1 induced let-7 was suppressed by transfection of locked nucleic acid (LNA) to inhibit let-7. Compared to normal lung cancer cells, over-expression of cofilin-1 suppressed the lung cancer migration, but simultaneously transfection of LNA recovered their migration ability to lungs in small animals. Taken together, over-expression of cofilin-1 can suppress the invasion and migration of lung cancer cells through up-regulation of let-7 in vitro and in vivo. Additionally, cofilin-1 may regulate EMT related transcription factors but not the whole EMT mechanism.
Cofilin-1; SNAIL-1; let-7; EMT; Reporter gene imaging; Locked nucleic acid
Wang CY, Tsai CH, Chang CY, Liao MJ, Liu RS, Lee YJ. Over-Expression of Cofilin-1 Suppressed Mobility of Lung Cancer Cells is Associated with DownRegulation of SNAIL-1 and Induction of Let-7. Clin Oncol. 2016; 1: 1015.