TY - JOUR

T1 - Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma

AU - Vaganova, Anastasia N.

AU - Kuvarzin, Savelii R.

AU - Sycheva, Anastasia M.

AU - Gainetdinov, Raul R.

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1/11

Y1 - 2022/1/11

N2 - 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.

AB - 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.

KW - Cancer

KW - Dopamine

KW - Melanoma

KW - Nevus

KW - TAAR1

KW - TAAR2

KW - TAAR5

KW - TAAR6

KW - TAAR8

KW - TAAR9

KW - Signal Transduction

KW - Humans

KW - Amines/metabolism

KW - Receptors, G-Protein-Coupled/genetics

KW - Melanoma/genetics

KW - DRUG

KW - nevus

KW - APOPTOSIS

KW - PHENOTHIAZINES

KW - CANCER

KW - PACKAGE

KW - SKIN

KW - MELANOCYTES

KW - melanoma

KW - IN-VIVO

KW - cancer

KW - dopamine

UR - http://www.scopus.com/inward/record.url?scp=85122706371&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/d7f5f7c0-1f75-3387-8466-8e552df6026d/

U2 - 10.3390/biom12010114

DO - 10.3390/biom12010114

M3 - Article

C2 - 35053262

AN - SCOPUS:85122706371

VL - 12

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 1

M1 - 114

ER -