LncRNA ZNF674-AS1 regulates granulosa cell glycolysis and proliferation by interacting with ALDOA.
Duan LiXiaoyan WangGuangyu LiYujie DangShidou ZhaoYingying QinPublished in: Cell death discovery (2021)
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.
Keyphrases
- long noncoding rna
- protein kinase
- single cell
- long non coding rna
- signaling pathway
- transcription factor
- poor prognosis
- cell therapy
- polycystic ovary syndrome
- skeletal muscle
- metabolic syndrome
- high resolution
- nitric oxide
- gene expression
- mesenchymal stem cells
- stress induced
- mass spectrometry
- heat stress
- binding protein
- endoplasmic reticulum