LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA

Granulosa cell (GC) is a critical somatic component of ovarian follicles to support oocyte development, while the regulatory role of long noncoding RNA (lncRNA) in GCs is largely unknown. Here, we identified a down-regulated lncRNA ZNF674-AS1 in GCs from patients with biochemical premature ovarian insufficiency (bPOI), and its expression correlates with serum levels of clinical ovarian reserve indicators. Functional experiments showed that ZNF674-AS1 is induced by energy stress, and regulates the proliferation and glycolysis of GCs, which possibly leads to follicular dysfunction. Mechanistically, low-expressed ZNF674-AS1 reduced the enzymatic activity of aldolase A (ALDOA), concomitant with promoting the association between ALDOA and v-ATPase to activate the lysosome localized AMP-activated protein kinase (AMPK). These findings identified a new lncRNA-ALDOA complex through which ZNF674-AS1 exerts its functions, expanding the understanding of epigenetic regulation of GCs function and POI pathogenesis.

Automated summary

The down-regulated lncRNA ZNF674-AS1 in granulosa cells (GC) from patients with biochemical premature ovarian insufficiency (bPOI) is induced by energy stress and regulates cell proliferation and glycolysis, potentially leading to follicular dysfunction. Additionally, ZNF674-AS1 exerts its functions through a new lncRNA-ALDOA complex, expanding the understanding of epigenetic regulation of GC function and POI pathogenesis.