MIR503HG impeded ovarian cancer progression by interacting with SPI1 and preventing TMEFF1 transcription

MIR503 host gene (MIR503HG) acts as an important tumor suppressor in many human cancers, but its role and regulatory mechanism in ovarian cancer need to be further studied. In this study, lower expressed MIR503HG was observed in ovarian tumor tissues and cells than in adjacent normal tissues and normal human ovarian epithelial cells. MIR503HG overexpression impaired the proliferative, invasive and EMT properties, and facilitated cell apoptosis in ovarian cancer cells. Nuclear and cytoplasmic separation test suggested that MIR503HG was mainly expressed in the nucleus. RNA immunoprecipitation and RNA pull-down assays confirmed that MIR503HG could bind to transcription factor SPI1 (Spi-1 proto-oncogene), and dual luciferase reporter gene and Chromatin immunoprecipitation assays verified that SPI1 could bind to TMEFF1 (Transmembrane protein with EGF like and two follistatin like domains 1) promoter, suggesting that MIR503HG suppressed TMEFF1 expression by competitively binding SPI1 and blocking transcriptional activation of TMEFF1. Moreover, interference with TMEFF1 reversed the promotion effect of MIR503HG silence on the malignant behaviors of ovarian cancer cells. Moreover, MIR503HG knockdown activated the MAPK and PI3K/AKT pathways by increasing the expression of TMEFF1. In addition, overexpression of MIR503HG in vivo suppressed the tumorigenic ability in nude mice. In conclusion, MIR503HG acted as a tumor suppressor lncRNA in ovarian cancer by suppressing transcription factor SPI1-mediated transcriptional activation of TMEFF1.