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

被引：72

作者：

Tsai, Cheng-Han ^{[1
]}

Lin, Liang-Ting ^{[1
]}

Wang, Chung-Yih ^{[2
]}

Chiu, Yu-Wen ^{[1
]}

Chou, Yen-Ting ^{[1
]}

Chiu, Shu-Jun ^{[7
]}

Wang, Hsin-Ell ^{[1
]}

Liu, Ren-Shyan ^{[1
,3
,4
]}

Wu, Chun-Yi ^{[1
]}

Chan, Pei-Chia ^{[1
,6
]}

Yang, Muh-Hwa ^{[5
]}

Chiou, Shih-Hwa ^{[5
,8
]}

Liao, Man-Jyun ^{[1
]}

Lee, Yi-Jang ^{[1
,6
]}

机构：

[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

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2015年 / 1852卷 / 05期

关键词：

NSCLC; Cofilin-1; Xenograft tumor model; Reporter gene imaging; Let-7; microRNA; EPITHELIAL-MESENCHYMAL TRANSITION; LUNG-CANCER; PROSTATE-CANCER; ACTIN; METASTASIS; FAMILY; MOTILITY; PATHWAY; REPRESSION; INHIBITION;

D O I：

10.1016/j.bbadis.2015.01.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

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.

引用

页码：851 / 861

页数：11

共 55 条

[1]

Proteins of the ADF/cofilin family: Essential regulators of actin dynamics [J].