Overexpression of VEGFA is known to modulate the AKT signaling cascade by activating the vascular endothelial growth factor receptor 1 (VEGFR1). Vascular endothelial growth factor A (VEGFA), a direct downstream target of miR-16-5p was suppressed by PVT1 knockdown in CRC cells.

Targeted loss of miR-16-5p partially rescues the suppressive effect induced by PVT1 knockdown. Furthermore, dual-luciferase reporter and RNA pull-down assay indicated that PVT1 binds to miR-16-5p, which has been shown to play strong tumor suppressive roles in CRC. In vitro means of PVT1 loss in a CRC cell line inhibits cell proliferation, migration and invasion.

In this study, we observe that upregulated PVT1 is associated with poor prognosis and bad clinicopathological features of CRC patients. However, the molecular basis for cancer initiation, development and progression remains unclear. Recently the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is reported to be involved in the pathogenesis of several cancers including human colorectal cancer (CRC). Significance between two groups (A) was tested by independent Student's t-tests significance between multiple independent groups (C-E) was tested by one-way ANOVA followed by post hoc Tukey's test. (F) Morphology images of STC-injured AR42J cells transfected with lncRNA-PVT1 shRNA plasmid (100 × magnification). (E) Amylase (n = 6), TNF-α, and IL-1β (n = 3) levels in STC-injured AR42J cells transfected with lncRNA-PVT1 shRNA plasmid. (D) Relative expression level of lncRNA-PVT1 in STC-injured AR42J cells transfected with lncRNA-PVT1 shRNA plasmid (n = 4). (C) Relative expression level of lncRNA-PVT1 in AR42J cells transfected with lncRNA-PVT1 shRNA plasmid (n = 4). (B) lncRNA-PVT1 expression in AR42J cells assayed by RNA FISH (630 × magnification). (A) Relative expression level of lncRNA-PVT1 in AR42J cells detected by real-time PCR (n = 3).

After a 48-hour transfection, the cells were cultured in the presence or absence of STC for 2-hours. AR42J cells were cultured in 6-well plates containing a serum-free medium and transfected with lncRNA shRNAs mixed with GP-transfect-Mate. Downregulation of lncRNA-PVT1 alleviated STC-induced AR42J cell injury.

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