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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Article

Tsai, Cheng-Han¹  Lin, Liang-Ting¹  Wang, Chung-Yih²  Chiu, Yu-Wen¹  Chou, Yen-Ting¹  Chiu, Shu-Jun⁷  Wang, Hsin-Ell¹  Liu, Ren-Shyan^1,3,4  Wu, Chun-Yi¹  Chan, Pei-Chia^1,6  Yang, Muh-Hwa⁵  Chiou, Shih-Hwa^5,8  Liao, Man-Jyun¹  Lee, Yi-Jang^1,6 

[1] Natl Yang Ming Univ, Dept Biomed Imaging & Radiol Sci, Taipei 112, Taiwan

[2] Cheng Hsin Gen Hosp, Dept Med Imaging, Radiotherapy, Taipei, Taiwan

[3] Taipei Vet Gen Hosp, Dept Nucl Med, Natl PET Cyclotron Ctr, Taipei, Taiwan

[4] Natl Yang Ming Univ, Sch Med, Mol & Genet Imaging Core, Taipei 112, Taiwan

[5] Natl Yang Ming Univ, Sch Med, Inst Clin Med, Taipei 112, Taiwan

[6] Natl Yang Ming Univ, BMIRC, Taipei 112, Taiwan

[7] Tzu Chi Univ, Dept Life Sci, Hualien, Taiwan

[8] Natl Yang Ming Univ, Inst Pharmacol, Taipei 112, Taiwan

关键词: NSCLC;    Cofilin-1;    Xenograft tumor model;    Reporter gene imaging;    Let-7 microRNA;   

DOI  :  10.1016/j.bbadis.2015.01.007

来源: Elsevier

【 摘 要 】

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 7 days. 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. (C) 2015 Elsevier B.V. All rights reserved.

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