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

Cheng Han Tsai, Liang-ting Lin, Chung Yih Wang, Yu Wen Chiu, Yen Ting Chou, Shu Jun Chiu, Hsin Ell Wang, Ren Shyan Liu, Chun Yi Wu, Pei Chia Chan, Muh Hwa Yang, Shih Hwa Chiou, Man Jyun Liao, Yi Jang Lee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

31 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)851-861
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number5
DOIs
Publication statusPublished - 1 May 2015
Externally publishedYes

Keywords

  • Cofilin-1
  • Let-7 microRNA
  • NSCLC
  • Reporter gene imaging
  • Xenograft tumor model

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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