MicroRNA-145 inhibits tumour growth and metastasis in colorectal cancer by targeting fascin-1

Abstract

Background:Recent studies have reported miR-145 dysregulated in colorectal cancer (CRC). In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues.Methods:The expression levels of miR-145 were analysed in CRC cell lines and tumour tissues by real-time PCR. A luciferase reporter assay confirmed direct targets. The functional effects of miR-145 were examined in transfected CRC cells in vitro and in vivo using established assays.Results:Downregulation of miR-145 was detected in most primary CRC tumours, and was significantly correlated with a more aggressive phenotype of CRC in patients. In CRC cell lines, ectopic overexpression of miR-145 inhibited cell proliferation, motility and invasion in vitro. Stable overexpression of miR-145 suppressed tumour growth and pulmonary metastasis in vivo. Further studies indicated that miR-145 may directly interact with the 3′-untranslated region (3′-UTR) of Fascin-1 messenger RNA (mRNA), downregulating its mRNA and protein expression levels. In clinical specimens, Fascin-1 expression was negatively correlated with miR-145 expression.Conclusions:MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1. This miRNA may be involved in the development and progression of CRC.

An exclusive cellular and molecular network governs intestinal smooth muscle cell differentiation in vertebrates

“…6L,M). Using luciferase assays, we next determined that miR-145 negatively regulated other target genes known to mediate migration, including podxl, fscn1a (fascin actin-bundling protein 1A) and fli1a (Feng et al, 2014;Larsson et al, 2009;Lin et al, 2014) (Fig. 5N).…”

Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1

“…3 Emerging evidence has shown that miRNAs are involved in cancer initiation and progression. 4 MiR-145 has been reported as an important tumor suppressor gene in ovarian carcinoma, 5,6,7 malignant pleural mesothelioma, 8 breast cancer, 9 pancreatic cancer, 10,11 liposarcoma, 12 colorectal cancer, 13,14,15,16 neuroblastoma, 17 breast cancer, 18,19,20,21 esophageal cancer, 22 bladder cancer, 23,24 urothelial cancer, 25 prostate cancer, 26,27 gastric cancer, 28 and head and neck cancer, 29 and other types. MiR-145 was also implicated in the progression of NSCLC; 30,31,32 however, its exact mechanism is not well established.…”

Aberrant expression of miRNAs predicts recurrence and survival in stage-II colorectal cancer patients from Egypt

“…miR-145 induces its functions partially via activating the PAK gene, an important oncogene that promotes cellular migration [20]. PAK overexpression associated significantly with aggressive tumor phenotypes and poor prognosis in CRC patients and therefore it represents a new prognostic factor those patients [10,[21][22][23]. The anti-tumor effect of miR-145 is achieved via targeting insulin receptor substrate-1, the docking protein of IGF1-R, with consequent inhibition of IGF1-R signaling in CRC [24].…”