title: Over-expression of cofilin-1 suppressed growth and invasion of cancer cells is associated with up-regulation of let-7 microRNA.
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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Liang-Ting
authors.initials: LT
authors.lastname: Lin
authors.affiliation: Radiotherapy, Department of Medical Imaging, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Chung-Yih
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Ting
authors.initials: YT
authors.lastname: Chou
authors.affiliation: Department of Life Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Department of Nuclear Medicine, National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taiwan; Molecular and Genetic Imaging Core, Medical School, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Chia
authors.initials: PC
authors.lastname: Chan
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Man-Jyun
authors.initials: MJ
authors.lastname: Liao
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan. Electronic address: yjlee2@ym.edu.tw.
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D051338:Cofilin 1 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D049268:Positron-Emission Tomography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging / Q000379:methods; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D015854:Up-Regulation
chemical_list: D051338:Cofilin 1; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Cofilin-1; Let-7 microRNA; NSCLC; Reporter gene imaging; Xenograft tumor model