Targeting steroid receptor RNA activator (SRA), a long non-coding RNA, enhances melanogenesis through activation of TRP1 and inhibition of p38 phosphorylation

Abnormal skin melanin homeostasis results in refractory pigmentary diseases. Melanogenesis is influenced by gene regulation, ultraviolet radiation, and host epigenetic responses. Steroid receptor RNA activator (SRA), a long noncoding RNA, is known to regulate steroidogenesis and tumorigenesis. Howev...

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Published inPloS one Vol. 15; no. 8; p. e0237577
Main Authors Ho, Ji-Chen, Lee, Chih-Hung, Hong, Chien-Hui
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 13.08.2020
Public Library of Science (PLoS)
Subjects
Antibodies
Biology and Life Sciences
Dermatology
Development and progression
DNA methylation
Gene regulation
Genetic aspects
Homeostasis
Interference
Kinases
Medicine and Health Sciences
Melanin
Melanoma
Non-coding RNA
Ovaries
Phosphorylation
Physical Sciences
Physiological aspects
Physiology
Pigmentation
Pigmentation disorders
Proteins
Receptors
Research and Analysis Methods
Ribonucleic acid
RNA
RNA-mediated interference
Statistical analysis
Steroid receptors
Steroidogenesis
Steroids
Transcription
Transcription factors
Tumorigenesis
Ultraviolet radiation
Taiwan
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Summary:Abnormal skin melanin homeostasis results in refractory pigmentary diseases. Melanogenesis is influenced by gene regulation, ultraviolet radiation, and host epigenetic responses. Steroid receptor RNA activator (SRA), a long noncoding RNA, is known to regulate steroidogenesis and tumorigenesis. However, how SRA contributes to melanogenesis remains unknown. Using RNA interference against SRA in B16 and A375 melanoma cells, we observed increased pigmentation and increased expression of TRP1 and TRP2 at transcriptional and translational levels only in B16 cells. The constitutive phosphorylation of p38 in B16-shCtrl cells was inhibited in cells with knocked down SRAi. Moreover, the melanin content of control B16 cells was increased by SB202190, a p38 inhibitor. Furthermore, reduced p38 phosphorylation, enhanced TRP1 expression, and hypermelanosis were observed in A375 cells with RNA interference. These results indicate that SRA-p38-TRP1 axis has a regulatory role in melanin homeostasis and that SRA might be a potential therapeutic target for treating pigmentary diseases.
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Competing Interests: All the authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0237577