Shao, Luying;
Zhao, Yibo;
Heinrich, Michael;
Prieto, Jose Maria;
Manzoni, Claudia;
(2023)
Active natural compounds perturb the melanoma risk-gene network.
G3
10.1093/g3journal/jkad274.
(In press).
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Abstract
Cutaneous melanoma is an aggressive type of skin cancer with a complex genetic landscape caused by the malignant transformation of melanocytes. This study aimed at providing an in-silico network model based on the systematic profiling of the melanoma-associated genes considering germline mutations, somatic mutations, and genome-wide association studies (GWAS) signals accounting for a total of 232 unique melanoma risk genes. A protein-protein interaction (PPI) network was constructed using the melanoma risk genes as seeds and evaluated to describe the functional landscape in which the melanoma genes operate within the cellular milieu. Not only were the majority of the melanoma risk genes able to interact with each other at the protein level within the core of the network, but this showed significant enrichment for genes whose expression is altered in human melanoma specimens. Functional annotation showed the melanoma risk network to be significantly associated with processes related to DNA metabolism and telomeres, DNA damage and repair, cellular ageing, and response to radiation. We further explored whether the melanoma risk network could be used as an in-silico tool to predict the efficacy of anti-melanoma phytochemicals, that are considered active molecules with potentially less systemic toxicity than classical cytotoxic drugs. A significant portion of the melanoma risk network showed differential expression when SK-MEL-28 human melanoma cells were exposed to the phytochemicals harmine and berberine chloride. This reinforced our hypothesis that the network modelling approach not only provides an alternative way to identify molecular pathways relevant to disease, but it may also represent an alternative screening approach to prioritize potentially active compounds.
| Type: | Article |
|---|---|
| Title: | Active natural compounds perturb the melanoma risk-gene network |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/g3journal/jkad274 |
| Publisher version: | https://doi.org/10.1093/g3journal/jkad274 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Melanoma, berberine chloride, differential gene expression, harmine, network analysis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10184465 |
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