Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA

• Published in: Biochimica et biophysica acta 2015-05, Vol.1852 (5), p.851-861
• Main Authors: Tsai, Cheng-Han, Lin, Liang-Ting, Wang, Chung-Yih, Chiu, Yu-Wen, Chou, Yen-Ting, Chiu, Shu-Jun, Wang, Hsin-Ell, Liu, Ren-Shyan, Wu, Chun-Yi, Chan, Pei-Chia, Yang, Muh-Hwa, Chiou, Shih-Hwa, Liao, Man-Jyun, Lee, Yi-Jang
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Cofilin 1 - genetics; Cofilin 1 - metabolism; Cofilin-1; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Let-7 microRNA; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Mice, Inbred NOD; Mice, SCID; MicroRNAs - genetics; Microscopy, Fluorescence; Neoplasm Invasiveness; NSCLC; Oligonucleotide Array Sequence Analysis; Positron-Emission Tomography; Reporter gene imaging; Reverse Transcriptase Polymerase Chain Reaction; Time-Lapse Imaging - methods; Transplantation, Heterologous; Tumor Burden - genetics; Up-Regulation; Xenograft tumor model
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2015.01.007

Cofilin-1, a non-muscle isoform of actin regulatory protein that belongs to the actin-depolymerizing factor (ADF)/cofilin family is known to affect cancer development. Previously, we found that over-expression of cofilin-1 suppressed the growth and invasion of human non-small cell lung cancer (NSCLC) cells in vitro. In this study, we further investigated whether over-expression of cofilin-1 can suppress tumor growth in vivo, and performed a microRNA array analysis to better understand whether specific microRNA would be involved in this event. The results showed that over-expression of cofilin-1 suppressed NSCLC tumor growth using the xenograft tumor model with the non-invasive reporter gene imaging modalities. Additionally, cell motility and invasion were significantly suppressed by over-expressed cofilin-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 affected after over-expression of cofilin-1 up to 7days. Knockdown of let-7b or let-7e using chemical locked nucleic acid (LNA) could recover the growth rate and the invasion of cofilin-1 over-expressing cells. Next, the expression of c-myc, LIN28 and Twist-1 proteins known to regulate let-7 were analyzed in cofilin-1 over-expressing cells, and Twist-1 was significantly suppressed under this condition. Up-regulation of let-7 microRNA by over-expressed cofilin-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 cofilin-1 mediated tumor suppression in vitro and in vivo. •Over-expression of cofilin-1 suppresses cell growth of NSCLC in vitro and in vivo.•Over-expression of cofilin-1 suppresses migration and invasion of NSCLC cells.•Let-7 microRNA mediates over-expression of cofilin-1 suppressed cell growth and invasion.•Twist-1 is involved in cofilin-1 over-expression induced let-7 expression.