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Altered hsa_circ_0005567 expression in schizophrenia: exploratory clinical associations and cellular evidence
Jiale Li1, Qingqing Zhong2, Jianxiong Long3
1Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China; Department of Epidemiology, School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China.
Background:
Schizophrenia (SCZ) is a chronic mental disorder with unknown etiology and complex pathophysiology. Circular RNAs (circRNAs) have emerged as important regulators in neuropsychiatric disorders. This study investigated the clinical relevance, functional role, and potential mechanism of hsa_circ_0005567 in SCZ.
Methods:
hsa_circ_0005567 expression was measured by qRT-PCR in peripheral blood mononuclear cells (PBMCs) from 160 patients with SCZ and 160 healthy controls. Associations with clinical symptoms and laboratory parameters were explored. Functional studies were conducted in MK-801-treated SH-SY5Y cells after hsa_circ_0005567 knockdown or overexpression. Cell viability, apoptosis, and inflammatory cytokines were assessed. Candidate hsa_circ_0005567-interacting proteins were explored using chromatin isolation by RNA purification (CHIRP), mass spectrometry, RNA immunoprecipitation, and Western blotting.
Results:
hsa_circ_0005567 expression was significantly increased in PBMCs from patients with SCZ (P < 0.001) and in SH-SY5Y cells following MK-801 treatment (P = 0.026). Higher hsa_circ_0005567 expression remained associated with SCZ status after adjustment for age and sex. Exploratory analyses of PANSS scores and laboratory parameters showed only nominal associations, none of which remained significant after FDR correction. In vitro, hsa_circ_0005567 manipulation affected cell viability, apoptosis, and TNF-α expression in MK-801-treated SH-SY5Y cells. RPL7A was identified as a candidate hsa_circ_0005567-interacting protein, and its protein expression was altered following hsa_circ_0005567 knockdown or overexpression.
Conclusions:
hsa_circ_0005567 is upregulated in PBMCs from patients with SCZ and is independently associated with SCZ status. Functional experiments suggest that hsa_circ_0005567 may participate in cellular responses under MK-801-induced stress conditions, while RPL7A represents a candidate interacting protein. Further clinical and mechanistic validation is needed.
