CircORC2 is involved in the pathogenesis of slow transit constipation via modulating the signalling of miR-19a and neurotensin/motilin.

Yuan-Yuan Wang, Rui-Yun Lu, Ji Shi, Shuai Zhao, Xia Jiang, Xiaosong Gu

Journal of cellular and molecular medicine 2021 Apr

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In this study, we aimed to investigate the role of circORC2 in modulating miR-19a and its downstream signalling during the pathogenesis of STC. In this study, three groups of patients, that is healthy control (HC) group, normal transit constipation (NTC) group (N = 42) and slow transit constipation (STC) group, were, respectively, recruited. RT-PCR and Western blot analysis were exploited to investigate the changes in the expression levels of miR-19a and circORC2 in these patients, so as to establish a circORC2/miR-19a signalling pathway. The basic information of the patients showed no significant differences among different patient groups. Compared with the HC group, concentrations of neurotensin (NST) and motilin (MLN) were both significantly reduced in the NTC and STC groups, especially in the STC group. Also, miR-19a level was highest, whereas circORC2 level was lowest in the STC group. Furthermore, circORC2 was validated to sponge the expression of miR-19a, and the transfection of circORC2 reduced the expression of miR-19a. Meanwhile, MLN and NST mRNAs were both targeted by miR-19a, and the transfection of circORC2 dramatically up-regulated the expression of MLN and NST. On the contrary, the transfection of circORC2 siRNA into SMCs and VSMCs exhibited the opposite effect of circORC2. Collectively, the results of this study established a regulatory relationship among circORC2, miR-19a and neurotensin/motilin, which indicated that the overexpression of circORC2 could up-regulate the levels of neurotensin and motilin, thus exerting a beneficial effect during the treatment of STC. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Yuan-Yuan Wang, Rui-Yun Lu, Ji Shi, Shuai Zhao, Xia Jiang, Xiaosong Gu. CircORC2 is involved in the pathogenesis of slow transit constipation via modulating the signalling of miR-19a and neurotensin/motilin. Journal of cellular and molecular medicine. 2021 Apr;25(8):3754-3764