Circ-ERC2 Is Involved in Melatonin Synthesis by Regulating the miR-125a-5p/MAT2A Axis

Abstract

The circadian rhythm of melatonin secretion in the pineal gland is highly conserved in vertebrates. Melatonin levels are always elevated at night. Acetylserotonin O-methyltransferase (ASMT) is the last enzyme in the regulation of melatonin biosynthesis (N-acetyl-5-hydroxytryptamine-melatonin). S-adenosylmethionine (SAM) is an important methyl donor in mammals and can be used as a substrate for the synthesis of melatonin. Methionine adenosyltransferase (MAT) catalyzes the synthesis of SAM from methionine and ATP and has a circadian rhythm. CircRNA is an emerging type of endogenous noncoding RNA with a closed loop. Whether circRNAs in the pineal gland can participate in the regulation of melatonin synthesis by binding miRNAs to target mat2a as part of the circadian rhythm is still unclear. In this study, we predicted the targeting relationship of differentially expressed circRNAs, miRNAs and mRNAs based on the results of rat pineal RNA sequencing. Mat2a siRNA transfection confirmed that mat2a is involved in the synthesis of melatonin. Circ-ERC2 and miR-125a-5p were screened out by software prediction, dual-luciferase reporter experiments, cell transfection, etc. Finally, we constructed a rat superior cervical ganglionectomy model (SCGx), and the results showed that circ-ERC2 could participate in the synthesis of melatonin through the miR-125a-5p/MAT2A axis. The results of the study revealed that circ-ERC2 can act as a molecular sponge of miR-125a-5p to regulate the synthesis of melatonin in the pineal gland by targeting mat2a. This experiment provides a basis for research on the circadian rhythm of noncoding RNA on pineal melatonin secretion.

Novel Insights into the Circadian Rhythms Based on Long Noncoding and Circular RNA Profiling

“…These observations indicate the potential of circRNAs in the regulation of circadian rhythm. Studies have demonstrated that circRNAs influence melatonin metabolism and circadian rhythm by sponging miRNAs in the pineal gland [20,56]. Cir-cRNA Cdr1as strongly regulates light entrainment during a 12:12 h light/dark cycle in the SCN tissue [21].…”

Circular RNA as a Novel Regulator and Promising Biomarker in Polycystic Ovary Syndrome

“…Melatonin or melatonin receptor 1A has been widely reported to improve PCOS by modulating AR and key metabolic enzymes [101]. An in vitro study showed that circ-ERC2 regulates rhythmic melatonin production in rat pineal glands via the miR-125a-5p/MAT2a axis [102]. In addition, animal experiments have shown that continuous light exposure leads to altered circRNA expression profiles in rat ovaries.…”