NEAT1 inhibits granulosa cell apoptosis and promotes cell growth and migration through the miR-130a-3p/BMP6 axis

What are the molecular mechanisms of action of nuclear paraspeckle assembly transcript 1 (NEAT1), miR-130a-3p and bone morphogenetic protein 6 (BMP6) in regulating ovarian granulosa cell (OGC) apoptosis and dysfunction in women with diminished ovarian reserve (DOR)?

Follicular fluid was collected from 20 women undergoing oocyte retrieval: 10 with DOR and 10 with normal ovarian reserve (NOR). OGC were isolated and assayed for expression of NEAT1, miR-130a-3p and BMP6. Granulosa-like tumour cell line (KGN) cells were used to investigate NEAT1 function by gene silencing and overexpression.

NEAT1 and BMP6 expression were significantly lower in DOR-derived OGC compared with NOR-derived OGC (P < 0.001), while miR-130a-3p expression was elevated (P < 0.001). NEAT1 expression was positively correlated with embryo number (r = 0.505, P = 0.023), number of high-quality embryos (r = 0.757, P < 0.001), two-pronuclei fertilization rate (r = 0.477, P = 0.033) and oocyte yield (r = 0.511, P = 0.021). Dual-Luciferase Reporter assays demonstrated that miR-130a-3p binds directly to NEAT1 and BMP6 3'UTR (P < 0.001). Functionally, NEAT1 overexpression significantly promoted the proliferation and migration of KGN cells, while suppressing apoptosis (P < 0.001); these effects were partially attenuated by miR-130a-3p mimic transfection. Conversely, inhibition of miR-130a-3p significantly reduced apoptosis, and enhanced proliferation and migration of KGN cells (P < 0.001); these effects were partially reversed upon BMP6 silencing.

NEAT1 inhibits apoptosis and promotes proliferation and migration of OGC through the miR-130a-3p/BMP6 axis, which may improve oocyte quality in patients with DOR. As such, NEAT1 may be a potential prognostic biomarker and therapeutic target for DOR.

ChiCTR2400079975.