Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?. (November 2013)

• Record Type: Journal Article
• Authors: Amodeo, Valeria; Bazan, Viviana; Fanale, Daniele; Insalaco, Lavinia; Caruso, Stefano; Cicero, Giuseppe; Bronte, Giuseppe; Rolfo, Christian; Santini, Daniele; Russo, Antonio
• Is Part Of: Expert opinion on therapeutic targets. Volume 17:Number 11(2013:Nov.)
• Page Start: 1249
• Page End: 1261
• Publication Date: 2013-11
• Subjects: Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1517/14728222.2013.832206
• Languages: English
• ISSNs: 1744-7631

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Objective:</italic> </bold> miRNAs are attractive molecules for cancer treatment, including colon rectal cancer (CRC). We investigate on the molecular mechanism by which miR-182 could regulate thrombospondin-1 (TSP-1) expression, a protein downregulated in CRC and inversely correlated with tumor vascularity and metastasis.</p> <p> <bold> <italic>Background:</italic> </bold> MicroRNAs are small non-coding RNAs that regulate the expression of different genes, involved in cancer progression, angiogenesis and metastasis. miR-182, over-expressed in colorectal cancer (CRC), has like predictive target thrombospondin-1 (TSP-1), a protein inversely correlated with tumor vascularity and metastasis that results downregulated in different types of cancer including CRC.</p> <p> <bold> <italic>Results:</italic> </bold> We found that TSP-1 increased after transfection with anti-miR-182 and we showed that miR-182 targets TSP-1 3′UTR-mRNA in both cells. Moreover, we observed that anti-miR-182 did not induce significant variation of Egr-1 expression, but affected the nuclear translocation and its binding on <italic>tsp-1</italic> promoter in HCT-116. Equally, Sp-1 was slightly increased as total protein, rather we found a nuclear accumulation and its loading on the TSP-1 promoter in HT-29 transfected with anti-miR-182.</p> <p> <bold> <italic>Conclusion:</italic> </bold> Our data suggest that miR-182 targets the anti-angiogenic factor TSP-1 and that anti-miR-182 determines an upregulation of TSP-1 expression in colon cancer cells. Moreover, anti-miR-182 exerts a transcriptional regulatory mechanism of <italic>tsp-1</italic> modulating Egr-1 and Sp-1 function. Anti-miR-182 could be used to restore TSP-1 expression in order to contrast angiogenic and invasive events in CRC.</p> </abstract>