Identification and characterization of N6-methyladenosine circular RNAs in the spinal cord of morphine-tolerant rats
Manyu Xing, Meiling Deng, Yufei Shi, Jiajia Dai, Tong Ding, Zongbin Song, Wangyuan Zou
Abstract
Morphine tolerance (MT) is a tricky problem, the mechanism of it is currently unknown. Circular RNAs (circRNAs) serve significant functions in the biological processes (BPs) of the central nervous system. N6-methyladenosine (m 6 A), as a key post-transcriptional modification of RNA, can regulate the metabolism and functions of circRNAs. Here we explore the patterns of m 6 A-methylation of circRNAs in the spinal cord of morphine-tolerant rats. In brief, we constructed a morphine-tolerant rat model, performed m 6 A epitranscriptomic microarray using RNA samples collected from the spinal cords of morphine-tolerant rats and normal saline rats, and implemented the bioinformatics analysis. In the spinal cord of morphine-tolerant rats, 120 circRNAs with different m 6 A modifications were identified, 54 of which were hypermethylated and 66 of which were hypomethylated. Functional analysis of these m 6 A circRNAs found some important pathways involved in the pathogenesis of MT, such as the calcium signaling pathway. In the m 6 A circRNA-miRNA networks, several critical miRNAs that participated in the occurrence and development of MT were discovered to bind to these m 6 A circRNAs, such as miR-873a-5p, miR-103-1-5p, miR-107-5p. M 6 A modification of circRNAs may be involved in the pathogenesis of MT. These findings may lead to new insights into the epigenetic etiology and pathology of MT.