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CircRNA ZNF609 promotes growth and metastasis of nasopharyngeal carcinoma by competing with microRNA-150-5p.

Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2817-2826. doi:10.26355/eurrev_201904_17558
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摘要


OBJECTIVE:This study aims to explore the biological function of circular RNA ZNF609 (circ-ZNF609) in regulating the occurrence and progression of nasopharyngeal carcinoma (NPC), and to investigate the possible underlying mechanism. PATIENTS AND METHODS:The expression levels of circ-ZNF609, microRNA-150-5p and Sp1 in NPC tissues and normal nasopharyngeal epithelial tissues were detected by quantitative Real (qRT-PCR). Circ-ZNF609 expression was silenced in NPC cell lines (5-8F and HONE-1). Cellular behaviors of NPC cells were determined using Cell Counting Kit-8 (CCK-8), wound healing and transwell assay. The binding relationship among microRNA-150-5p, circ-ZNF609 and Sp1 was detected by Dual-Luciferase reporter gene assay. In addition, the protein expression of Sp1 after altering expression of circ-ZNF609 or microRNA-150-5p was detected by Western blot. RESULTS:The expression levels of circ-ZNF609 and Sp1 in NPC tissues were markedly higher than those of normal nasopharyngeal epithelial tissues. However, the expression of microRNA-150-5p was significantly lower in NPC tissues. The knockdown of circ-ZNF609 in NPC cells 5-8F and HONE-1 significantly inhibited the proliferative, migratory and invasive behaviors of NPC cells. Meanwhile, microRNA-150-5p knockdown in NPC cells showed the opposite effect on cellular behaviors of NPC cells. Dual-Luciferase reporter gene assay revealed that circ-ZNF609 could bind to microRNA-150-5p, and Sp1 was a target gene of microRNA-150-5p. Western blot results showed that circ-ZNF609 could stabilize the expression of Sp1, while microRNA-150-5p degraded Sp1 expression. Furthermore, the knockdown of Sp1 in NPC cells reversed the carcinogenic effect of circ-ZNF609. CONCLUSIONS:Highly expressed circ-ZNF609 adsorbs microRNA-150-5p to upregulate Sp1 expression, thereby promoting the proliferation and metastatic ability of NPC cells.

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