LncRNA XIST inhibits ovarian cancer cell growth and metastasis via regulating miR-150-5p/PDCD4 signaling pathway
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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 miR-150-5p 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.
KeywordsXIST miR-150-5p PDCD4 Metastasis Ovarian cancer
Guanzhen Li designed the study, performed the experiments, and analyzed the data.
Shuli Wang performed the experiments, analyzed the data, and wrote the paper.
Compliance with ethical standards
The protocol for the current study was reviewed by the Clinical Research Ethics Committee of the Provincial Hospital Affiliated to Shandong University (No. 20180725), and written consent was obtained from all patients.
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