Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex
The various roles of microRNAs (miRNAs) in controlling the phenotype of cancer cells are the focus of contemporary research efforts. We have recently shown that miR-17 directly targets the ADAR1 gene and thereby enhances melanoma cell aggressiveness. miR-17 and miR-20a belong to the miR-17/92 comple...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2014-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140030 |
| _version_ | 1811313415256276992 |
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| author | Eyal Greenberg Steven Hajdu Yael Nemlich Ronit Cohen Orit Itzhaki Jasmine Jacob-Hirsch Michal J. Besser Jacob Schachter Gal Markel |
| author_facet | Eyal Greenberg Steven Hajdu Yael Nemlich Ronit Cohen Orit Itzhaki Jasmine Jacob-Hirsch Michal J. Besser Jacob Schachter Gal Markel |
| author_sort | Eyal Greenberg |
| collection | DOAJ |
| description | The various roles of microRNAs (miRNAs) in controlling the phenotype of cancer cells are the focus of contemporary research efforts. We have recently shown that miR-17 directly targets the ADAR1 gene and thereby enhances melanoma cell aggressiveness. miR-17 and miR-20a belong to the miR-17/92 complex, and their mature forms are identical except for two non-seed nucleotides. Nevertheless, here we show that these two miRNAs carry markedly different effects on melanoma cells. A strong positive correlation was observed between the expression of miR-17 and miR-20a among various melanoma cultures. Luciferase assays showed that miR-17 but not miR-20a directly targets the 3’ untranslated region of the ADAR1 gene. Ectopic expression of these miRNAs in melanoma cells differentially alters the expression of five exemplar TargetScan-predicted target genes: ADAR1, ITGB8, TGFBR2, MMP2 and VEGF-A. Whole-genome expression microarrays confirm a markedly differential effect on the transcriptome. Functionally, over-expression of miR-20a but not of miR-17 in melanoma cells inhibits net proliferation in vitro. The differential functional effect was observed following ectopic expression of the mature miRNA or of the pre-miRNA sequences. This suggests that the two non-seed nucleotides dictate target sequence recognition and overall functional relevance. These miRNAs are clearly not redundant in melanoma cell biology. |
| first_indexed | 2024-04-13T10:54:29Z |
| format | Article |
| id | doaj.art-68e7dfb435a645eab4bc88a37fb7c1c2 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-04-13T10:54:29Z |
| publishDate | 2014-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-68e7dfb435a645eab4bc88a37fb7c1c22022-12-22T02:49:34ZengThe Royal SocietyOpen Biology2046-24412014-01-014610.1098/rsob.140030140030Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complexEyal GreenbergSteven HajduYael NemlichRonit CohenOrit ItzhakiJasmine Jacob-HirschMichal J. BesserJacob SchachterGal MarkelThe various roles of microRNAs (miRNAs) in controlling the phenotype of cancer cells are the focus of contemporary research efforts. We have recently shown that miR-17 directly targets the ADAR1 gene and thereby enhances melanoma cell aggressiveness. miR-17 and miR-20a belong to the miR-17/92 complex, and their mature forms are identical except for two non-seed nucleotides. Nevertheless, here we show that these two miRNAs carry markedly different effects on melanoma cells. A strong positive correlation was observed between the expression of miR-17 and miR-20a among various melanoma cultures. Luciferase assays showed that miR-17 but not miR-20a directly targets the 3’ untranslated region of the ADAR1 gene. Ectopic expression of these miRNAs in melanoma cells differentially alters the expression of five exemplar TargetScan-predicted target genes: ADAR1, ITGB8, TGFBR2, MMP2 and VEGF-A. Whole-genome expression microarrays confirm a markedly differential effect on the transcriptome. Functionally, over-expression of miR-20a but not of miR-17 in melanoma cells inhibits net proliferation in vitro. The differential functional effect was observed following ectopic expression of the mature miRNA or of the pre-miRNA sequences. This suggests that the two non-seed nucleotides dictate target sequence recognition and overall functional relevance. These miRNAs are clearly not redundant in melanoma cell biology.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140030mir-17mir-20amelanomamir-17-92 clusterproliferationdifferential regulation |
| spellingShingle | Eyal Greenberg Steven Hajdu Yael Nemlich Ronit Cohen Orit Itzhaki Jasmine Jacob-Hirsch Michal J. Besser Jacob Schachter Gal Markel Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex Open Biology mir-17 mir-20a melanoma mir-17-92 cluster proliferation differential regulation |
| title | Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex |
| title_full | Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex |
| title_fullStr | Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex |
| title_full_unstemmed | Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex |
| title_short | Differential regulation of aggressive features in melanoma cells by members of the miR-17-92 complex |
| title_sort | differential regulation of aggressive features in melanoma cells by members of the mir 17 92 complex |
| topic | mir-17 mir-20a melanoma mir-17-92 cluster proliferation differential regulation |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.140030 |
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