| Abstrakt: |
Background: Circular RNA itchy E3 ubiquitin protein ligase (circ‐ITCH) has previously been reported to play a key role in carcinogenesis. Nevertheless, the role of circ‐ITCH in nasopharyngeal carcinoma (NPC) remains to be explored. Methods: Gene expression analysis was performed using a quantitative real‐time polymerase chain reaction, western blotting and immunohistochemistry. The role of circ‐ITCH in NPC was explored using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide, colony formation, transwell invasion, scratch healing and xenograft tumor assays. Furthermore, luciferase reporter assay was carried out to assess the interactions among circ‐ITCH, microRNA‐214 (miR‐214) and phosphatase and tensin homolog (PTEN). Results: The levels of circ‐ITCH and PTEN were decreased, whereas the level of miR‐214 was increased in NPC tissues collected from 28 subjects compared to normal nasopharynx tissues collected from 15 subjects. Moreover, a negative correlation between circ‐ITCH and miR‐214 expression and a positive correlation between circ‐ITCH and PTEN expression were observed in NPC tissues. Downregulation of circ‐ITCH expression was also observed in NPC cell lines. In addition, upregulation of circ‐ITCH markedly inhibited NPC cell proliferation, migration and invasion. Furthermore, circ‐ITCH was confirmed to exert its function by sponging miR‐214. PTEN was found to be a direct target gene of miR‐214 and its expression was negatively correlated with miR‐214 expression in NPC tissues. Moreover, our results showed that the circ‐ITCH/miR‐214 axis regulated NPC proliferation, migration and invasion through regulating the expression of PTEN. Upregulation of circ‐ITCH or PTEN blocked miR‐214‐mediated promotion of NPC tumorigenesis in vitro. Additionally, upregulation of circ‐ITCH also suppressed NPC tumorigenesis in vivo. Conclusions: The present study demonstrated that circ‐ITCH suppressed NPC tumorigenesis by upregulating PTEN expression through interacting with miR‐214, thus proposing a novel mechanism for NPC inhibition. [ABSTRACT FROM AUTHOR] |
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