Downregulated lncRNA HOTAIR ameliorates polycystic ovaries syndrome via IGF-1 mediated PI3K/Akt pathway.

OBJECTIVE

Polycystic ovarian syndrome (PCOS) is a common disorder that leads to infertility in reproductive-aged females. HOTAIR is highly expressed in various gynecological diseases and is associated with a poor prognosis. We aimed to explore the role of HOTAIR in PCOS.

METHODS

First, PCOS rats were induced using dehydroepiandrosterone and then treated with si-HOTAIR. Next, HOTAIR mRNA expression and serum hormone levels were detected. HE staining was applied to observe estrus cycle, ovarian morphology and count the number of follicles. Apoptosis in the ovary was detected by TUNEL. Thereafter, ovarian granulosa cells (GCs) were isolated from PCOS rats, transfected with si-HOTAIR and treated with LY294002 (Akt inhibitor) or IGF-1. CCK-8 and flow cytometry assays were used to evaluate cell viability and apoptosis. IGF-1, apoptosis- and PI3K/Akt pathway-associated protein expressions in ovary and GCs were also detected.

RESULTS

In experiments, si-HOTAIR decreased serum T, E and LH levels but increased FSH level, restored estrus cycle, ovarian morphology and inhibited apoptosis of ovary in PCOS rats. Meanwhile, assays showed that si-HOTAIR upregulated the viability but inhibited the apoptosis of PCOS GCs. Furthermore, both and assays revealed that si-HOTAIR increased Bcl-2 expression but suppressed Bax, Bad, IGF-1 expressions and PI3K, AKT phosphorylation. However, the aforementioned effects of si-HOTAIR were further enhanced by LY294002 and partially reversed by IGF-1.

CONCLUSIONS

HOTAIR knockdown improved PCOS, and the mechanism may relate to IGF-1-mediated PI3K/Akt pathway, indicating HOTAIR may be a novel therapeutic target for PCOS.