Down-regulation of MALAT1 aggravates polycystic ovary syndrome by regulating MiR-302d-3p-mediated leukemia inhibitory factor activity

Abstract

AimsAccumulating evidence have shown the important roles of long noncoding RNA (lncRNA) in controlling different diseases. In the present study, we tried to explore the role which lncRNA MALAT1 plays in polycystic ovary syndrome (PCOS) with the involvement of microRNA-302d-3p (miR-302d-3p) and leukemia inhibitory factor (LIF). MethodsA PCOS rat model was established and characterized, followed by treatment with si-MALAT1, oe-MALAT1, miR-302d-3p mimic, or miR-302d-3p inhibitor constructs. Serum hormonal levels were detected to evaluate endocrine conditions. The effect of MALAT1 and miR-302d-3p on activities of ovarian granulosa cells was assessed, as well as the involvement of LIF. ResultsMALAT1 expression was shown to be downregulated in ovarian tissue of PCOS rats. Overexpression of MALAT1 in vitro promoted proliferation and inhibited apoptosis of ovarian granulosa cells. Overexpression of MALAT1 in vivo reduced the ovarian tissue injury and endocrine disorders accompanied with decreased level of FSH and elevated serum levels of E2, T, and LH in the PCOS rat. Overexpression of MALAT1 also promoted the expression of LIF, which could be reversed by overexpression of miR-302d-3p, indicating that MALAT1 up-regulated the expression of LIF via miR-302d-3p. Furthermore, overexpression of MALAT1 reduced endocrine disorders and ovarian tissue damage via the miR-302d-3p/LIF axis. ConclusionOur study highlighted that MALAT1 plays a protective role in reducing ovarian tissue damage and endocrine disorder in PCOS by regulating the miR-302d-3p/LIF axis.