• J Pain · Mar 2023

    Spinal circKcnk9 regulates chronic visceral hypersensitivity of irritable bowel syndrome.

    • Zhong Chen, Yuan Liu, Xianhe Wu, Wei Lin, Zihan Liu, Yang Huang, Yu Chen, Ying Tang, Aiqin Chen, and Chun Lin.
    • Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
    • J Pain. 2023 Mar 1; 24 (3): 463477463-477.

    AbstractDysregulation of circular RNAs (circRNAs) has been reported to be functionally associated with chronic pain, but it is unknown whether and how circRNAs participate in visceral hypersensitivity. The expression of circKcnk9 was increased in spinal neurons of irritable bowel syndrome (IBS)-like rats. ShcircKcnk9 attenuated visceral hypersensitivity and inhibited c-Fos expression in IBS-like rats, whereas overexpression of spinal circKcnk9 induced visceral hypersensitivity and increased c-Fos expression in control rats. Furthermore, circKcnk9 was found to act as a miR-124-3p sponge. MiR-124-3p antagomir restored pain responses downregulated by shcircKcnk9 in IBS-like rats. Finally, the signal transducer and activator of transcription 3 (STAT3), validated as a target of miR-124-3p, could play a critical role in visceral hypersensitivity by regulating NSF/GluR2. PERSPECTIVE: Spinal circKcnk9 functions as a miR-124-3p sponge to promote visceral hypersensitivity by regulating the STAT3/NSF/GluR2 pathway. This pathway might provide a novel epigenetic mechanism of visceral hypersensitivity and a potential circRNA therapeutic target for IBS.Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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