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.

Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis

“…let-7 family members have a distinct expression pattern in animal development, largely regulated by the RNA-binding protein Lin28, with let-7 expression repressed in the embryonic stages of development (16)(17)(18). The let-7/lin28 axis has been implicated as a master regulator of cell proliferation and differentiation, with reduced let-7 miRNA expression reported in epithelial-to-mesenchymal transition and enhanced cell migration/invasion (19,20).…”

Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients

“…It has been reported that the Let‐7 family associated with the growth and invasion of malignant tumours including NPC . Interestingly, we found eight Let‐7 members (namely hsa‐let‐7a‐5p, hsa‐let‐7b‐5p, hsa‐let‐7c, hsa‐let‐7d‐5p, hsa‐let‐7e‐5p, hsa‐let‐7f‐5p, hsa‐let‐7g‐5p, hsa‐let‐7i‐5p) were down‐regulated in early stage of NPC and 1 member (hsa‐let‐7d‐3p) was down‐regulated in all stages of NPC.…”

Mesothelioma Interactome with 367 Novel Protein-Protein Interactions

“…The interaction of ACTB which is usually synthesized in response to guidance cues, with CFL1 that promotes disassembly of actin filaments may also be disrupted in MPM (93,94). Overexpression of CFL1 suppresses the growth of non-small cell lung cancer tumor, through suppression of cell motility and invasion (95). Thus, we conclude that the novel interaction of DPYSL2 with TUBA4A and its involvement in SEMA3A-mediated signaling may throw light on the role played by axon guidance signaling in mesothelioma.…”