HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth
In addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (<i>ELAVL1</i>) is able to bind and stabilize a large group of target mRNAs, which contain AU-rich elements (ARE) in their 3′-untranslated r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/5/1299 |
| _version_ | 1797567366442254336 |
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| author | Janika K. Liebig Silke Kuphal Anja Katrin Bosserhoff |
| author_facet | Janika K. Liebig Silke Kuphal Anja Katrin Bosserhoff |
| author_sort | Janika K. Liebig |
| collection | DOAJ |
| description | In addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (<i>ELAVL1</i>) is able to bind and stabilize a large group of target mRNAs, which contain AU-rich elements (ARE) in their 3′-untranslated region. We found HuR to be upregulated in malignant melanoma in vitro and in vivo, significantly correlating with progression in vivo. Additionally, we could show that miR-194-5p can regulate HuR expression level. HuR knockdown in melanoma cells led to the suppression of proliferation and the induction of cellular senescence. Interestingly, HuR overexpression was sufficient to inhibit senescence in <i>BRAF<sup>V600E</sup></i>-expressing melanocytes and to force their growth. Here, MITF (Microphthalmia-associated transcription factor), a key player in suppressing senescence and an ARE containing transcript, is positively regulated by HuR. Our results show for the first time that the overexpression of HuR is an important part of the regulatory pathway in the development of malignant melanoma and functions as a switch to overcome oncogene-induced senescence and to support melanoma formation. These newly defined alterations may provide possibilities for innovative therapeutic approaches. |
| first_indexed | 2024-03-10T19:41:49Z |
| format | Article |
| id | doaj.art-79b7953733c24955a235dd72ede22c53 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:41:49Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-79b7953733c24955a235dd72ede22c532023-11-20T01:12:20ZengMDPI AGCancers2072-66942020-05-01125129910.3390/cancers12051299HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma GrowthJanika K. Liebig0Silke Kuphal1Anja Katrin Bosserhoff2Institute of Biochemistry, Emil-Fischer Zentrum, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer Zentrum, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Biochemistry, Emil-Fischer Zentrum, Friedrich-Alexander University of Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyIn addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (<i>ELAVL1</i>) is able to bind and stabilize a large group of target mRNAs, which contain AU-rich elements (ARE) in their 3′-untranslated region. We found HuR to be upregulated in malignant melanoma in vitro and in vivo, significantly correlating with progression in vivo. Additionally, we could show that miR-194-5p can regulate HuR expression level. HuR knockdown in melanoma cells led to the suppression of proliferation and the induction of cellular senescence. Interestingly, HuR overexpression was sufficient to inhibit senescence in <i>BRAF<sup>V600E</sup></i>-expressing melanocytes and to force their growth. Here, MITF (Microphthalmia-associated transcription factor), a key player in suppressing senescence and an ARE containing transcript, is positively regulated by HuR. Our results show for the first time that the overexpression of HuR is an important part of the regulatory pathway in the development of malignant melanoma and functions as a switch to overcome oncogene-induced senescence and to support melanoma formation. These newly defined alterations may provide possibilities for innovative therapeutic approaches.https://www.mdpi.com/2072-6694/12/5/1299malignant melanomaHuRoncogene induced senescenceMITFMicrophthalmia-associated transcription factor |
| spellingShingle | Janika K. Liebig Silke Kuphal Anja Katrin Bosserhoff HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth Cancers malignant melanoma HuR oncogene induced senescence MITF Microphthalmia-associated transcription factor |
| title | HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth |
| title_full | HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth |
| title_fullStr | HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth |
| title_full_unstemmed | HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth |
| title_short | HuRdling Senescence: HuR Breaks BRAF-Induced Senescence in Melanocytes and Supports Melanoma Growth |
| title_sort | hurdling senescence hur breaks braf induced senescence in melanocytes and supports melanoma growth |
| topic | malignant melanoma HuR oncogene induced senescence MITF Microphthalmia-associated transcription factor |
| url | https://www.mdpi.com/2072-6694/12/5/1299 |
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