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CAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.

ABSTRACT: Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the melanocortin 1 receptor (MC1R) is a major melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing genomic stability and pharmacologic opportunities to reduce melanoma risk based on those insights. In this chapter, we review melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.

SUBMITTER: Holcomb NC

PROVIDER: S-EPMC7048968 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.

Holcomb Nathaniel C NC Bautista Robert-Marlo RM Jarrett Stuart G SG Carter Katharine M KM Gober Madeline Krentz MK D'Orazio John A JA

Advances in protein chemistry and structural biology 20181205

Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated ...[more]

PMID: 30798934

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Project description:BackgroundMelanoma is a common tumor characterized by a high mortality rate in its late stage. After metastasis, current treatment methods are relatively ineffective. Many studies have shown that long noncoding RNA (lncRNA) may participate in gene mutation and genomic instability in cancer.MethodsWe downloaded transcriptome data, mutation data, and clinical follow-up data of melanoma patients from The Cancer Genome Atlas. We divided samples into groups according to the number of somatic cell mutations and then performed a differential analysis to screen out the differentially expressed genes. We then divided samples into genomic unstable and genomic stable groups. We compared lncRNA expression profiles in these groups and constructed a protein-coding genes network coexpressed with selected lncRNA to analyze the pathways enriched by these genes. Two machine learning methods, least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE), were applied to conduct the lncRNA-related prognostic model. Afterward, we performed survival analysis, risk correlation analysis, independent prognostic analysis, and clinical subgroup model validation. Finally, through wound healing assay and transwell assay, the function of AATBC was verified by A375 cell lines.ResultsWe screened 61 prognostic-related lncRNAs and constructed an lncRNA-mRNA coexpression network based on these lncRNAs. Seven lncRNAs were selected as common characteristic factors based on the two machine learning methods. The model formula was as follows: risk score = 0.085∗AATBC + 0.190∗ AC026689.1-0.117∗AC083799.1 + 0.036∗ AC091544.6-0.039∗ LINC01287-0.291∗ SPRY4.AS1 + 0.056∗ ZNF667.AS1. The seven lncRNAs in this formula are key candidates. Cell experiments have verified that knocking down AATBC in A375 cell lines can reduce the proliferation and invasion ability of melanoma cells.ConclusionThe lncRNA we identified provides a new way to study lncRNA's role in the genomic instability of melanoma. Our findings may provide essential candidate biomarkers for the diagnosis and treatment of melanoma.

Dataset Information

CAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.

Publications

cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.

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