早发性卵巢功能不全是常见的女性生殖内分泌疾病之一，对女性生育能力产生不良影响，但其病因和发病机制仍然不明。近年来，越来越多的研究关注在长链非编码RNA在早发性卵巢功能不全中的作用。长链非编码RNA DANCR参与细胞分化和多种癌症。它在卵巢中高表达，但其在早发性卵巢功能不全中的作用仍未知。在这里，我们鉴定了一种新的与早发性卵巢功能不全相关的长链非编码RNA-DANCR，它负面影响卵泡颗粒细胞的老化和卵泡萎缩。DANCR在早发性卵巢功能不全患者的颗粒细胞中被证明表达减少。此外，我们研制并鉴定了Dancr基因敲除小鼠，与Dancr +/+小鼠相比，这些小鼠表现出了早发性卵巢功能不全表型和生育能力下降。进一步的体外实验表明，颗粒细胞中DANCR的沉默导致细胞老化和一系列与衰老有关的变化，包括增殖抑制、细胞周期G1阻滞和DNA损伤。机制研究揭示DANCR与hNRNPC和p53结合，而DANCR的沉默减弱了hNRNPC和p53的结合，从而增强了p53蛋白水平，显著促进了颗粒细胞的老化。这种新鉴定的长链非编码RNA DANCR通过调节hNRNPC-p53交互作用抑制了p53依赖的颗粒细胞老化，最终反抗了早发性卵巢功能不全。这为早发性卵巢功能不全的发病机制提供了新的见解，并为未来的诊断和治疗提供了潜在的靶点。© 2023作者。

Premature ovarian insufficiency (POI) is one of the common women reproductive endocrine diseases which adversely impacts female fertility, but the etiology and pathogenesis still remain elusive. Recently increasing researches focus on the roles of lncRNA in POI. LncRNA DANCR was involved in cell differentiation and multiple cancers. It's highly expressed in ovary while the role of DANCR in POI is still unknown.Here, we identify a new POI related lncRNA DANCR, which negatively contributes to ovarian granulosa cells aging and follicular atresia. DANCR is proved to be decreasingly expressed in POI patients' granulosa cells. Additionally, Dancr knockout (Dancr-/-) mice were constructed and characterized with POI phenotypes and fertility decline, compared with Dancr+/+ mice. Further, in vitro experiments indicated that DANCR knockdown in granulosa cells led to cell aging and series of aging-related changes including proliferation inhibition, cell cycle G1 arrest and DNA damage. Mechanism research revealed DANCR binds with hNRNPC and p53, while DANCR knockdown attenuates the binding of hNRNPC and p53, thus enhancing protein level of p53 and promoting granulosa cells aging significantly.The newly identified lncRNA DANCR inhibits p53-dependent granulosa cells aging by regulating hNRNPC-p53 interaction, and eventually counteracting POI. This provides new insights into the pathogenesis of POI and provides a potential target for future diagnosis and treatment.© 2023. The Author(s).