Modulation of the lncRNA TCONS_00265853-miR-421-5p-CLOCK axis by Ziyin Buyang Formula in polycystic ovarian syndrome with circadian rhythm disruption: an integrated bioinformatics and experimental approach
Year: 2025
Type: article
Abstract: Background Polycystic ovarian syndrome (PCOS), a common endocrine disorder in reproductive-aged women, is linked to circadian rhythm disruption, but the molecular mechanisms remain unclear. Dysregulation of the lncRNA TCONS_00265853-miR-421-5p-CLOCK axis may play an important role. Ziyin Buyang Formula (ZYBYF), a Traditional Chinese Medicine (TCM) targeting kidney Yin-Yang balance, shows therapeutic potential, though its mechanism is unclear. This study explores ZYBYF’s role in modulating this axis to improve circadian-disrupted PCOS. Methods Network pharmacology identified ZYBYF’s bioactive components and targets, integrated with PCOS-associated genes and circadian disruption-related differentially expressed genes (DEGs) from ovarian tissues. A continuous light-induced PCOS rat model (10-week 24-h light exposure) was employed to validate ZYBYF’s effects. Interventions included ZYBYF treatment. Results Bioinformatics identified 25 intersection targets, with MAPK signaling as the central pathway. In vivo, circadian disruption downregulated lncRNA TCONS_00265853 and CLOCK, elevated miR-421-5p, and hyperactivated MAPK (p-p38, p-ERK1/2, p-JNK), exacerbating ovarian apoptosis (↑BAX, ↓Bcl-2, p < 0.001). ZYBYF restored circadian axis components (↑TCONS_00265853, CLOCK; ↓miR-421-5p), suppressed MAPK activation, and normalized ovarian morphology and hormonal profiles (↓LH, T, ACTH; ↑E2, FSH, p < 0.001). PRKCA expression, a MAPK regulator, was rescued by ZYBYF, counteracting dysregulation of IL1B, VEGFA, and TGFB1. Conclusion Circadian disruption exacerbates PCOS via the TCONS_00265853-miR-421-5p-CLOCK axis, driving MAPK hyperactivation and ovarian apoptosis. ZYBYF reverses these effects, restoring hormonal balance and follicular dynamics. This study provides mechanistic validation of ZYBYF’s efficacy, positioning it as a promising therapeutic strategy for circadian-disrupted PCOS. These findings suggest that ZYBYF may modulate circadian rhythm–related pathways in PCOS via the lncRNA–miRNA–CLOCK axis, warranting further mechanistic validation.
Source: Frontiers in Genetics
Authors: Haixia Huang, Ling Sun, Fan Jia, Yong Tan, Yahong Zhou
Institution: Nanjing University of Chinese Medicine
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G5851352880
OpenAlex ID: W4414923295