Cell Death Discovery (May 2021)

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

  • Duan Li,
  • Xiaoyan Wang,
  • Guangyu Li,
  • Yujie Dang,
  • Shidou Zhao,
  • Yingying Qin

DOI
https://doi.org/10.1038/s41420-021-00493-1
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 12

Abstract

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Abstract 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.