Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis.

PURPOSE

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been revealed to involve in the progression of CRC. However, the precise mechanisms of PVT1 in action remain unclear.

METHODS

The expression of PVT1, microRNA-106b-5p (miR-106b-5p) and four jointed box 1 () was measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay. Transwell assay was used to determine cell migration and invasion. The correlation between miR-106b-5p and PVT1 or was confirmed using luciferase reporter assay. The effects of PVT1 in vivo were assessed using mice xenograft model.

RESULTS

PVT1 was up-regulated in CRC tissues and cell lines, especially in CRC tissues with high-grade, and highly expressed PVT1 predicted worse prognosis. Functional experiments demonstrated that PVT1 deletion inhibited CRC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. MiR-106b-5p was confirmed to be a target of PVT1, and inhibition of miR-106b-5p reversed the inhibitory effects of PVT1 knockdown on CRC cell malignant phenotypes. In addition, we found miR-106b-5p directly targeted , and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate expression via targeting miR-106b-5p.

CONCLUSION

Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/ axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.