BJECTIVE: 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. BACKGROUND: 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. RESULTS: 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 tsp-1 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. CONCLUSION: 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 tsp-1 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.

Amodeo, V., Bazan, V., Fanale, D., Insalaco, L., Caruso, S., Cicero, G., et al. (2013). Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?. EXPERT OPINION ON THERAPEUTIC TARGETS, 17(11), 1249-1261 [10.1517/14728222.2013.832206].

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

AMODEO, Valeria;BAZAN, Viviana;FANALE, Daniele;INSALACO, Lavinia;CARUSO, Stefano;CICERO, Giuseppe;BRONTE, Giuseppe;RUSSO, Antonio;CARRECA, Ignazio
2013

Abstract

BJECTIVE: 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. BACKGROUND: 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. RESULTS: 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 tsp-1 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. CONCLUSION: 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 tsp-1 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.
Settore MED/06 - Oncologia Medica
Amodeo, V., Bazan, V., Fanale, D., Insalaco, L., Caruso, S., Cicero, G., et al. (2013). Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?. EXPERT OPINION ON THERAPEUTIC TARGETS, 17(11), 1249-1261 [10.1517/14728222.2013.832206].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/98786
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