Long noncoding RNA NEAT1 decreases polycystic ovary syndrome progression via the modulation of the microRNA-324-3p and BRD3 axis.

ABSTRACT

Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is believed to be involved in many gynecological and obstetrics disorders. Nevertheless, the role of NEAT1 in polycystic ovary syndrome (PCOS) is scarcely investigated. Our study aimed to investigate the role of NEAT1, microRNA (miR)-324-3p, and bromodomain containing 3 (BRD3) in PCOS. First, 80 women with PCOS and 80 healthy (non-PCOS) women were included, and their serum hormone levels were tested. Next, the PCOS mouse model was established by dehydroepiandrosterone injection, and then NEAT1, miR-324-3p, and BRD3 expression levels were detected in the PCOS mice. Lentivirus carrying short hairpin-NEAT1 or miR-324-3p agomir was injected into the PCOS mice to determine the change in biochemical indices and pathology. Moreover, a rescue experiment was conducted, after which, the binding relationships among NEAT1, miR-324-3p, and BRD3 were analyzed. NEAT1 and BRD3 were expressed at a high level while miR-324-3p was expressed at a low level in women with PCOS and PCOS mice. Reduced levels of NEAT1 or elevated levels of miR-324-3p mitigated metabolic disorders and alleviated ovarian pathological changes in PCOS mice. Mechanistically, NEAT1 sponged miR-324-3p and miR-324-3p targeted BRD3. In the rescue experiment, elevated miR-324-3p or reduced BRD3 level reversed the effects of the enhanced NEAT1 on metabolic disorders and ovarian pathological changes in PCOS mice. NEAT1 exacerbates metabolic disorders and ovarian pathological changes in PCOS mice by downregulating miR-324-3p and upregulating BRD3. This study gives a novel direction in PCOS treatment.