RETRACTED ARTICLE: LncRNA XIST inhibits ovarian cancer cell growth and metastasis via regulating miR-150-5p/PDCD4 signal

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ORIGINAL ARTICLE

LncRNA XIST inhibits ovarian cancer cell growth and metastasis via regulating miR-150-5p/PDCD4 signaling pathway Shuli Wang 1 & Guanzhen Li 2 Received: 30 April 2019 / Accepted: 4 January 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract The aim of this study was to explore the role of X-inactive specific transcript (XIST), miR-150-5p, and programmed cell death protein 4 (PDCD4) in the pathogenesis of ovarian cancer (OC). The expression levels of XIST, miR-150-5p, and PDCD4 were examined by qRT-PCR or Western blotting as appropriate. The proliferation, apoptosis, migration, and invasiveness of human OC cell lines in vitro were respectively evaluated by CCK-8, TUNEL, wound-healing assay, and transwell assay. A xenograft model of OC was also established to determine the effect of XIST knockdown on tumor growth in vivo. Finally, direct binding between XIST and miR-150-5p and between miR-150-5p and PDCD4 were verified by dual-luciferase reported assay. XIST was significantly downregulated in OC tissues and cell lines compared with the normal ovarian epithelial tissues and cells. XIST knockdown in OC cells significantly facilitated cell growth, migration, and invasion and inhibited apoptosis. In addition, silencing XIST also initiated epithelial-mesenchymal transition (EMT) and conferred cancer stem cell (CSC) survival in vitro. Consistent with the in vitro findings, knockdown of XIST promoted tumorigenesis, suppressed PDCD4, and upregulated miR150-5p in vivo. XIST directly bound to and downregulated miR-150-5p in OC tissues and cell lines. Furthermore, PDCD4 was identified as the target gene of miR-150-5p, and XIST knockdown downregulated PDCD4 by relieving miR-150-5p inhibition. Finally, blocking miR-150-5p partly abolished the effects of XIST knockdown in vitro. Taken together, XIST inhibits OC growth and metastasis by upregulating PDCD4 via miR-150-5p suppression. Keywords XIST . miR-150-5p . PDCD4 . Metastasis . Ovarian cancer

Introduction Ovarian cancer (OC) is one of the most commonly diagnosed cancers in women, and its fatality rate is highest among female cancer patients worldwide (Coburn et al., 2017; Torre et al., 2018). Due to the lack of effective and accurate diagnostic markers, the patients are often diagnosed at an advanced stage with extensive metastases, invasion, and epithelial to mesenchymal transition (EMT) (Torre et al., 2018). The loss of epithelial phenotype and gain of the mesenchymal phenotype are an important process in solid cancer development and are associated with cancer cell stemness (Hardin et al., 2017),

* Guanzhen Li [email protected] 1

Department of Imaging, Provincial Hospital Affiliated to Shandong University, Jinan 250000, Shandong, China

2

Department of Oncology, Provincial Hospital Affiliated to Shandong University, Jinan 250000, Shandong, China

metastasis, and invasion (Pavan et al., 2018; Zhang et al., 2018a). Recent studies show that a rare subpopulation of tumor cells with stem cell–like properties, designated as cancer ste