Angiogenesis Driven by the CEBPD-hsa-miR-429-VEGFA Signaling Axis Promotes Urothelial Carcinoma Progression

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Title:	Angiogenesis Driven by the CEBPD-hsa-miR-429-VEGFA Signaling Axis Promotes Urothelial Carcinoma Progression
Authors:	Chan, Ti-Chun Hsing, Chung-Hsi Shiue, Yow-Ling Huang, Steven K. Hsieh, Kun-Lin Kuo, Yu-Hsuan Li, Chien-Feng
Contributors:	Chi Mei Hospital National Health Research Institutes - Taiwan National Sun Yat Sen University Department of Biotechnology, Chia Nan University of Pharmacy & Science College of Pharmacy and Science, Chia Nan University of Pharmacy & Science
Keywords:	endothelial growth-factor targeted therapy c/ebp-delta cancer bevacizumab inhibition resistance cisplatin vegfa
Date:	2022
Issue Date:	2023-12-11 13:57:44 (UTC+8)
Publisher:	MDPI
Abstract:	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). 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. 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.
Relation:	CELLS, v.11, n.4, 638
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles [Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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