Background
Non-small cell lung cancer (NSCLC) is a common malignancy over the world. Previous report indicated that the plasmacytoma variant translocation 1 (PVT1) has been documented to function as an oncogene in various types of human cancers. However, the biological mechanism of PVT1 was still rarely reported in NSCLC.
Conclusion
These results manifested that PVT1 modulated BAMBI to promote tumor progression in NSCLC by sponging miR-17-5p. Thus, the novel regulatory pathway may provide a new therapeutic target for NSCLC patients.
Methods
The levels of PVT1, miR-17-5p, and bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) in NSCLC tissues (n=64) and cells (H1299 and A549) were detected by qRT-PCR and immunohistochemistry (IHC). The protein level of BAMBI was measured by Western blot assay. Cell viability and apoptotic rate were evaluated by MTT assay and flow cytometry, respectively. The migrated and invaded abilities were assessed by Transwell assay and Wound healing assay. The interactions between miR-17-5p and PVT1 or BAMBI were predicted by starBase v2.0 and TargetScan, respectively, and then dual-luciferase reporter assay and RNA pull-down assay were performed to verify these interactions. The mice model experiments were constructed to further validate the roles of PVT1 in vivo.
Results
The levels of PVT1 and BAMBI were both apparently increased, and miR-17-5p was declined in NSCLC tissues and cells. The depletion of PVT1 or BAMBI blocked cell viability, migrated and invaded abilities but impelled apoptotic rate in A549 and H1299 cells. PVT1 was validated as a sponge to miR-17-5p and BAMBI was a direct target of miR-17-5p. PVT1 promoted cell viability, migrated and invaded abilities but repressed apoptotic rate by targeting BAMBI. MiR-17-5p regulated cell behaviors mediated by PVT1. PVT1 silencing decreased BAMBI expression by sponging miR-17-5p. In addition, PVT1 knockdown blocked the xenograft tumor growth in vivo.