National Yang-Ming University, Taiwan
Cheng-Han Tsai has completed his PhD from National Yang-Ming University and now is the fi rst year Post-doctoral studies from the same institute. His studies focuses on changes of physiological characteristics as well as related genes profi le including miRNA of lung cancer cell in vitro and in vivo while the actin associated protein, ADF/cofi lin is manipulated. Some of studies have been published on reputed journals and other manuscripts are under prepared for further submissions
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.