Endometriosis (EMs) is a gynecological disease that seriously harms the women's health of childbearing age [1], which is defined as the growth of endometrial tissue (glands and stroma) outside the uterine cavity and myometrium [2]. However, the pathogenesis of EMs has not yet been elucidated. Autophagy and epithelial-mesenchymal transformation (EMT) are the main biological processes of cancer [3]. Autophagy is important for endometrial cell migration and invasion via EMT induction. Moreover, hypoxia is a vital microenvironmental factor leading to EMs, which can promote EMs autophagy and epithelial-mesenchymal transition (EMT) [4]. In implanted ectopic endometriotic lesions, hypoxia may play a role in retrograde endometrial cell survival and angiogenesis [5]. However, the molecular characteristics of EMs in a hypoxic environment have not been fully elucidated.

MicroRNAs are a class of evolutionarily conserved non-coding small RNAs that regulate gene expression at the translation level and play a vital role in the occurrence and development of EMs [6]. A previous study revealed that miR-200c inhibited EMs through targeting MALAT1 [7]. In murine models, overexpression of miR-202-3p attenuated EMs-like lesions via modulating YAP-dependent S100A6 transcription [8]. Additionally, it was reported that miR-150-5p was up-regulated in the serum of EMs patients [9], [10]. The miR-150-5p role in hypoxia-induced CRL-7566 cells has not yet been reported, which remains to be studied. It was reported that in colorectal cancer, miR-150-5p suppressed tumor progression via targeting VEGFA [11]. What’s more, miR-150-5p retarded myocardial fibrosis progression by targeting EGR1 [12]. In our paper, we predicted that miR-150-5p had binding sites with PDCD4. The miR-150-5p and PDCD4 regulatory relationship in EMs has not been reported, which needs further study in this study.

Programmed cell death 4 (PDCD4) is a newly discovered tumor suppressor. At the transcription and translation levels, PDCD4 played an essential role in inhibiting tumorigenesis and tumor progression. Studies have shown that PDCD4 expression was down-regulated in patients with EMs [13]. Autophagy is a mechanism that may alter anoikis [14]. Hypoxia lead to an increase in lncRNA-MALAT1, which activated the pro-survival autophagy pathway, thereby reducing apoptosis of EMs cells [15]. PDCD4 inhibited endometrial cell proliferation, migration, and invasion via inhibiting autophagy and NF-κB/MMP2/MMP9 signaling pathway [16]. Furthermore, microRNA-21 regulated the ERK/NF-κB signaling pathway by targeting PDCD4, which affected human melanoma A375 cells proliferation, migration, and apoptosis [17]. Hydrogen sulfide was reported to promote endometrial stromal cell proliferation in EMs by activating the NF-κB signaling pathway [18]. Lipoxin A4 down-regulated NF-κB signaling-mediated autophagy to inhibit endometrial stromal cell invasion and migration [19]. However, PDCD4 and NF-κB signaling pathway role in EMs remains unclear.

To sum up, our results revealed that knockdown of miR-150-5p reduced hypoxia-induced autophagy and EMT of endometriotic cells by promoting PDCD4 expression and inhibiting NF-κB signaling pathway activation, which might provide a new strategy for the diagnosis and treatment of EMs.