MALAT1 is involved in the pathophysiological process of PCOS by modulating TGFβ signaling in granulosa cells

Polycystic ovary syndrome (PCOS) is an endocrine disorder, the etiology of which is complex and unclear. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a conserved long non-coding RNA which has been found to play a role in the pathophysiological process of reproductive system diseases, such as endometriosis and pregnancy loss. However, the role of MALAT1 in PCOS is still unknown. In this study, reduced MALAT1 expression was found in granulosa cells (GCs) from 68 patients with PCOS and 30 healthy controls, which relates to upregulated cell proliferation and downregulated apoptosis. Using phosphorylation pathway profiling array, MALAT1 reduction was identified to contribute to the repression of transforming growth factor beta (TGFβ) signaling in GCs. Subsequently, MALAT1 was confirmed to function as a competing endogenous RNA (ceRNA), interacting with miR-125b and miR-203a. Meanwhile, miR-125b and miR-203a was identified as two novel TGFβ signaling negative regulators by targeting TGFBR1 and TGFBR2. Finally, MALAT1 knockdown was found to induce the upregulation of miR-125b and miR-203a, which further repressed TGFβ signaling, changed some downstream gene expression, and resulted in a disordered cell cycle. In conclusion, MALAT1 reduction was identified in GCs, which may contribute to the pathophysiological processes of PCOS by regulating TGFβ signaling through sponging miR-125b and miR-203a.