Cheng-Han Tsai
National Yang-Ming University, Taiwan
Title: Title: Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA
Biography
Biography: Cheng-Han Tsai
Abstract
Cofi lin-1, a non-muscle isoform of actin regulatory protein that belongs to the actin-depolymerizing factor (ADF)/cofi lin family is known to aff ect cancer development. Previously, we found that over-expression of cofi lin-1 suppressed the growth and invasion of human Non-Small Cell Lung Cancer (NSCLC) cells in vitro. In this study, we further investigated whether overexpression of cofi lin-1 can suppress tumor growth in vivo, and performed a microRNA array analysis to better understand whether specifi c microRNA would be involved in this event. Th e results showed that over-expression of cofi lin-1 suppressed NSCLC tumor growth using the xenograft tumor model with the non-invasive reporter gene imaging modalities. Additionally, cell motility and invasion were signifi cantly suppressed by over-expressed cofi lin-1, and down-regulation of Matrix Metalloproteinase (MMPs) 1 and 3 was concomitantly detected. According to the microRNA array analysis, the let-7 family, particularly let-7b and let-7e, were apparently up-regulated among 248 microRNAs that were aff ected aft er over-expression of cofi lin-1 up to 7 days. Knock-down of let-7b or let-7e using chemical Locked Nucleic Acid (LNA) could recover the growth rate and the invasion of cofi lin-1 overexpressing cells. Next, the expression of c-myc, LIN28 and Twist-1 proteins known to regulate let-7 were analyzed in cofi lin-1 overexpressing cells, and Twist-1 was signifi cantly suppressed under this condition. Up-regulation of let-7 microRNA by overexpressed cofi lin-1 could be eliminated by co-transfected Twist-1 cDNA. Taken together, current data suggest that let-7 microRNA would be involved in over-expression of cofi lin-1 mediated tumor suppression in vitro and in vivo.
