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Circ-SFMBT2 sponges miR-224-5p to induce ketamine-induced cystitis by up-regulating metadherin (MTDH)

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Abstract

There is increasing evidence that circular RNAs (circRNAs) play significant roles in various biological processes, yet few reports have examined their roles and molecular mechanisms in ketamine-induced cystitis (KIC). This study examines the possible molecular mechanisms underlying the circRNA-microRNA-mRNA regulatory network in the development of KIC. Transcriptome data were collected, and bioinformatics analysis was conducted to create a circRNA-miRNA-mRNA regulatory network (ceRNA network) associated with the occurrence of KIC. Human bladder epithelial cells (SV-HUC-1) were used in in vitro cell assays. The binding affinity among circ-SFMBT2, miR-224-5p, and Metadherin (MTDH) was identified. To investigate the effects of circ-SFMBT2/miR-224-5p/MTDH on bladder function, KIC mouse models were induced by intraperitoneal injection of ketamine, and gain- or loss-of-function experiments were conducted. Our results demonstrate that MTDH may be a key gene involved in the occurrence of KIC. Both bioinformatics analysis and in vitro cell assays verified that circ-SFMBT2 can competitively bind to miR-224-5p, and miR-224-5p can target and inhibit MTDH. In the bladder tissues of KIC mice, circ-SFMBT2 and MTDH were up-regulated, while miR-224-5p was down-regulated. Animal experiments further confirmed that circ-SFMBT2 can up-regulate MTDH expression by sponging miR-224-5p, thereby exacerbating bladder dysfunction in KIC mice. This study proved that circ-SFMBT2 up-regulates MTDH by competitively binding to miR-224-5p, thereby exacerbating the bladder dysfunction of KIC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by Hainan Provincial Natural Science Foundation of China (821MS120).

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Authors and Affiliations

  1. Department of Urology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Hainan Province, 19 Xiuhua Road, Xiuying District, Haikou, 570311, People’s Republic of China

    Fanchang Zeng, Qinghui Wu, Mi Song, Xinli Kang, Zhewen Ou, Zuobing Yang & Daoyuan Li

  2. Department of Scientific Research, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311, China

    Liumei Luo

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  1. Fanchang Zeng
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Contributions

FZ conceived and designed research. QW performed experiments. MS interpreted results of experiments. XK analyzed data. ZO prepared Figures. ZY drafted paper. LL and DL edited and revised manuscript. All authors read and approved final version of manuscript.

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Correspondence to Daoyuan Li.

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The authors declare that they have no competing interests.

Ethical approval

Animal experiments were carried out according to the scheme approved by the Animal Experiment Committee of our Hospital. The animal experiments have complied with the appropriate ethical standards to minimize the pain and discomfort caused to the animals. The mice underwent standardized care and protection throughout the study. Additionally, relevant anesthetization and pain relief protocols were strictly followed to minimize the animals' pain and distress.

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Zeng, F., Wu, Q., Song, M. et al. Circ-SFMBT2 sponges miR-224-5p to induce ketamine-induced cystitis by up-regulating metadherin (MTDH). Human Cell 36, 2040–2054 (2023). https://doi.org/10.1007/s13577-023-00972-w

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