Figure 3.

(a) MALAT1 was identified as a sponge of miR-200c. This regulation is not restricted to miR-200c and might include the entire miR-200 family (miR-200s), consisting of miR-200a, miR-200b, miR-200c, miR-141, and miR-429. Upregulation of MALAT1 in women with endometriosis leads to enhanced sponging of miR200s and promotes zinc finger E-box binding homeobox transcription factor 1 (ZEB1) and ZEB2 expression leading to higher EMT. In HESCs, the lncRNA MALAT1 directly interacts with miR-126-5p, which regulates cAMP responsive element-binding protein (CREB1) expression. Upregulation of MALAT1 inhibits apoptosis probably via activation of the PI3K–AKT pathway through the miR-126-5p–CREB1 axis. MALAT1 lncRNA can also lead to reduced apoptosis in HESCs through the upregulation of the NFkB/iNOS signaling pathway activity, which also enhances migration and invasion of cells. In cultured primary endometrial stromal cells, MALAT1 leads to upregulation of hypoxia-induced autophagy. In this signaling cascade, regulation of MALAT1 expression is under the control of the HIF1α transcription factor. (b) In granulosa cells (GCs) of women with endometriosis, significant downregulation of MALAT1 expression was reported. MALAT1 knockdown induced an increase in phosphorylated ERK1/2 (p-ERK1/2) that was associated with altered follicle count, due to impaired cell proliferation resulting from ERK/MAPK-dependent activation of p21/p53 cell cycle arrest. In an autograft transplantation rat model of endometriosis, inhibition of the lncRNA BANCR led to a decrease in ectopic tissue volume associated with a significant reduction in serum levels of VEGF, MMP-2, and MMP-9, ERK, and MAPK mRNA and in phosphorylated ERK and MAPK protein levels in tissues. HESCs: human endometrial stromal cells.