Hurdling senescence: hur breaks braf-induced senescence in melanocytes and supports melanoma growth

Liebig J, Kuphal S, Boßerhoff AK (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cancers MDPI

Book Volume: 12

Article Number: 1299

Journal Issue: 5

DOI: 10.3390/cancers12051299

Abstract

In addition to genetic changes, post-transcriptional events strongly contribute to the progression of malignant tumors. The RNA-binding protein HuR (ELAVL1) 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 BRAFV600E -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.

Authors with CRIS profile

Janika Liebig Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung (IZKF)

Related research project(s)

D031 (Biochemie u. Mol. Medizin: Modulation of oncogene-induced senescence by cell-matrix adhesion March 16, 2020 - March 15, 2023

How to cite

APA:

Liebig, J., Kuphal, S., & Boßerhoff, A.K. (2020). Hurdling senescence: hur breaks braf-induced senescence in melanocytes and supports melanoma growth. Cancers, 12(5). https://doi.org/10.3390/cancers12051299

MLA:

Liebig, Janika, Silke Kuphal, and Anja Katrin Boßerhoff. "Hurdling senescence: hur breaks braf-induced senescence in melanocytes and supports melanoma growth." Cancers 12.5 (2020).

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