Background
Long noncoding RNA X inactivate-specific transcript (lncRNA XIST) has been identified to contribute to the development and progression of non-small cell lung cancer (NSCLC). Thus, it is important to explore more specific functions and molecular mechanisms of XIST in NSCLC tumorigenesis. Materials and
Conclusion
XIST suppresses cell tumorigenicity in human NSCLC by regulating miR-142-5p/PAX6 axis, which indicates a novel insight into the pathogenesis of NSCLC and lays a foundation for the molecular therapy of NSCLC.
Methods
The expression of XIST, microRNA (miR)-142-5p and paired box 6 (PAX6) was measured using quantitative real-time polymerase chain reaction or Western blot, respectively. Cell proliferation was analyzed using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to measure apoptotic cells. Cell migration and invasion were determined by Transwell assay. The interaction between miR-142-5p and XIST or PAX6 was confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo experiments were performed through the murine xenograft model.
Results
XIST was elevated in NSCLC, and XIST knockdown suppressed cell proliferation, migration, invasion and induced apoptosis in vitro as well as repressed tumor growth in vivo. MiR-142-5p was a target of XIST, and silencing miR-142-5p reversed the anti-tumor functions mediated by XIST knockdown in NSCLC cells. PAX6 was confirmed to be a target of miR-142-5p, and the inhibitory effects caused by miR-142-5p restoration in NSCLC cell malignant phenotypes were attenuated by PAX6 overexpression. Besides that, XIST could indirectly regulate PAX6 expression by sponging miR-142-5p in vivo and in vitro.