Background and purpose
This research aimed to excavate the alternative mechanism of CEBPD on tumor growth and explore the biological significance of the CEBPD/hsa-miR-429/VEGFA axis on angiogenesis in urothelial carcinoma (UC).
Conclusions
We decipher the oncogenic mechanism of CEBPD on angiogenesis through the hsa-miR-429 inhibition to stabilize the expression of VEGFA in UC. The novel research unveiled the modulation of the CEBPD/hsa-miR-429/VEGFA axis on the progression of UC and could be accessible to theranostic biomarkers.
Methods
Quantitative RT-PCR, immunoblotting assay and tube formation examined the effect of hsa-miR-429 mimic or/and inhibitor on VEGFA expression and angiogenesis in CEBPD-overexpressing UC-derived cells. The association between CEBPD, hsa-miR-429, VEGFA and microvascular density (MVD) and clinical outcome were evaluated in 296 patients with UBUC and 340 patients with UTUC, respectively.
Purpose
This research aimed to excavate the alternative mechanism of CEBPD on tumor growth and explore the biological significance of the CEBPD/hsa-miR-429/VEGFA axis on angiogenesis in urothelial carcinoma (UC).
Results
The increase in the transcript and protein of VEGFA as well as HUVECs tube formation was diminished upon the treatment of hsa-miR-429 mimic in CEBPD-overexpressing BFTC909 and TCCSUP. Nevertheless, the inhibited regulation of hsa-miR-429 mimic on the expression of VEGFA and ability of HUVECs tube formation was rescued by the combined incubation with hsa-miR-429 inhibitor in these two UC-derived cell lines. Furthermore, the clinical correlations showed that the higher level of VEGFA or MVD has a positive correlation with the expression of CEBPD and a negative relation to hsa-miR-429 and leads to tumor aggressiveness with worse disease-specific, metastasis-free survival in UBUC and UTUC cohorts. Conclusions: We decipher the oncogenic mechanism of CEBPD on angiogenesis through the hsa-miR-429 inhibition to stabilize the expression of VEGFA in UC. The novel research unveiled the modulation of the CEBPD/hsa-miR-429/VEGFA axis on the progression of UC and could be accessible to theranostic biomarkers.