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 (FJX1 ) 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 FJX1  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 FJX1 , and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by FJX1  up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate FJX1  expression via targeting miR-106b-5p.
Conclusion: Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/FJX1  axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.
Keywords: colorectal cancer, PVT1, miR-106b-5p, FJX1 , metastasis, apoptosis