Identification of the ceRNA networks in α-MSH-induced melanogenesis of melanocytes.

Ling Jiang, Jinhua Huang, Yibo Hu, Li Lei, Yujie Ouyang, Yan Long, Hui Li, Si Li, Lun Yang, Yan Yang, Lihua Huang, Hong Xiang, Rong Xiao, Jing Chen, Qinghai Zeng

Aging 2020 Dec 14

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α-MSH is known for melanogenesis stimulation, and ceRNA is a new method involved in physiological regulation. However, whether ceRNA participates in α-MSH-induced melanogenesis remains unknown. We used ceRNA array to detect the expression profiles of lncRNAs, circRNAs, and mRNAs in melanocytes after α-MSH treatment. Moreover, the melanogenesis-related ceRNA regulatory networks were screened and validated. The expression profile analysis showed that 20 lncRNAs and 49 circRNAs changed five-fold after α-MSH treatment, while 933 mRNAs changed two-fold. Based on differentially expressed genes, GO and KEGG analysis were conducted and revealed that 14 genes were enriched in melanogenesis. Then, multiple lncRNA or circRNA-miRNA-mRNA ceRNA networks and lncRNA/circRNA-miRNA-mRNA quaternary ceRNA networks were identified. Thereinto, ENST00000606533, circ_0091223, and TYR expression were upregulated in α-MSH-treated melanocytes, while their complementary miR-1291 was decreased. Dual-luciferase reporter assay further verified that ENST00000606533 and circ_0091223 could bind to miR-1291. ENST00000606533 and circ_0091223 siRNAs decreased circ_0091223, ENST00000606533, and TYR expression, but increased miR-1291 expression. Conversely, miR-1291 mimics inhibited ENST00000606533, circ_0091223, and TYR expression. Moreover, miR-1291 inhibitor could reverse the inhibitory effect of the two siRNAs on TYR expression. Hence, the "ENST00000606533/circ_0091223-miR-1291-TYR" ceRNA network is involved in α-MSH-induced melanogenesis, and ceRNA networks may be potential therapeutic targets for skin pigmentation disorders.

Citation

Ling Jiang, Jinhua Huang, Yibo Hu, Li Lei, Yujie Ouyang, Yan Long, Hui Li, Si Li, Lun Yang, Yan Yang, Lihua Huang, Hong Xiang, Rong Xiao, Jing Chen, Qinghai Zeng. Identification of the ceRNA networks in α-MSH-induced melanogenesis of melanocytes. Aging. 2020 Dec 14;13(2):2700-2726