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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1431923
This article is part of the Research Topic Use of Bioinformatics in Pharmacogenetics to Optimize Drug Efficacy View all articles

Transcriptome analysis to explore the mechanism of downregulated TNIK influencing the effect of risperidone

Provisionally accepted
Ruixue Yuan Ruixue Yuan 1Yaojing Li Yaojing Li 2Xiangyi Li Xiangyi Li 3Ying M. Fu Ying M. Fu 1Ailing Ning Ailing Ning 1Dongxiang Wang Dongxiang Wang 1Ran Zhang Ran Zhang 1Shunying YU Shunying YU 1*Qingqing Xu Qingqing Xu 1
  • 1 Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China
  • 2 958 Hospital of the People's Liberation Army, Chongqing, Chongqing Municipality, China
  • 3 Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China

The final, formatted version of the article will be published soon.

    Risperidone is one of the most reliable and effective antipsychotics for schizophrenia treatment. However, the mechanism of action of risperidone is not yet fully understood. Traf2 and Nckinteracting protein kinase (TNIK), a schizophrenia susceptibility gene, is associated with risperidone treatment response. Our previous in vitro experiments confirmed that downregulated TNIK affected the effect of risperidone on downstream targets. However, the effect of downregulated TNIK on risperidone-induced molecular expression remains to be further explored. Hence, transcriptome analysis was performed on U251 cells subjected to risperidone, TNIK siRNA, and no treatment, respectively. Compared to the no-treatment group, two groups of DEGs were screened out and then intersected with the schizophrenia-related genes to screen the cross-talk genes. Those DEGs were analyzed using GO and KEGG. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network for the cross-talk gene. The result showed that the parathyroid hormone synthesis, secretion, and action were significantly enriched after risperidone treatment. Downregulated TNIK could have an impact on the collagen-containing extracellular matrix, signaling receptor activator activity, and PI3K-Akt signaling pathway. Interestingly, bone mineralization function and calcium signaling pathway were enriched in the cross-talk genes. Additionally, FGFR2, FGF1, and FGFR might be the potential targets for TNIK affecting the effects of risperidone. In conclusion, the study indicated that risperidone primarily influences functions and/or pathways associated with bone metabolism, potentially contributing to the adverse effect of osteoporosis. Our study may offer a novel perspective on investigating the mechanisms underlying the adverse effects of risperidone.

    Keywords: Risperidone, Traf2 and Nck-interacting protein kinase (TNIK), transcriptome analysis, protein-protein interaction, bone mineralization

    Received: 13 May 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Yuan, Li, Li, Fu, Ning, Wang, Zhang, YU and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shunying YU, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China

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