Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma.

Anastasia N Vaganova,Savelii R Kuvarzin,Anastasia M Sycheva,Raul R Gainetdinov

doi:10.3390/biom12010114

Abstract

Trace amine-associated receptors (TAARs) interact with amine compounds called “trace amines” which are present in tissues at low concentrations. Recently, TAARs expression in neoplastic tumors was reported. In this study, TAARs expression was analyzed in public RNAseq datasets in nevi and melanoma samples and compared to the expression of dopamine receptors (DRDs) that are known to be involved in melanoma pathogenesis. It was found that all DRDs and TAARs are expressed in nevi at comparable levels. Differential expression analysis demonstrated the drastic decrease of TAAR1, TAAR2, TAAR5, TAAR6, and TAAR8 expression in melanomas compared to benign nevi with only TAAR6, TAAR8, and TAAR9 remaining detectable in malignant tumors. No association of TAARs expression levels and melanoma clinicopathological characteristics was observed. TAARs co-expressed genes in melanoma and nevi were selected by correlation values for comparative pathway enrichment analysis between malignant and benign neoplasia. It was found that coexpression of TAARs with genes inquired in neurotransmitter signaling is lost in melanoma, and tumor-specific association of TAAR6 expression with the mTOR pathway and inflammatory signaling is observed. It is not excluded that TAARs may have certain functions in melanoma pathogenesis, the significance of which to tumor progression is yet to be understood.

Highlights

All TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and all dopamine receptors, were identified in nevi samples included in this dataset
DRD2, DRD3, DRD5, and all identified Trace amine-associated receptors (TAARs) were significantly downregulated in melanomas compared to nevi samples with the most drastic changes noted in TAARs (Figure 1, p < 0.05)
Differential gene expression analysis revealed a prominent decrease in TAARs expression in malignant melanoma compared to benign melanocytic nevi where all TAARs were expressed at levels comparable to dopamine receptors

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Melanoma is a malignant neoplasm of the melanocytes, with development considered a consequence of an interaction between genetic susceptibility and environmental exposure [1]. Intensive ultraviolet (UV) irradiation with consequent skin injury and DNA damage is presumed the major risk factor for melanocyte malignization [2]. Other risk factors for melanoma are the presence of melanocytic nevi and some genetic variants, the being genes involved in cell cycle regulation [3,4]. Mutated melanoma becomes resistant to radiotherapy and cytotoxic agents; the importance of revealing the specific therapeutic targets involved in melanoma genesis and progression

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