miR-195-5p Reduces VEGFA Expression and Angiogenesis in Colorectal Cancer
- 1National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy
Abstract
Angiogenesis is a key process in colorectal cancer (CRC) progression, with vascular endothelial growth factor A (VEGFA) being a major pro-angiogenic mediator. miR-195-5p has previously been identified by our group as a tumor-suppressive miRNA downregulated in CRC. Here, we aimed to investigate whether miR-195-5p contributes to CRC-associated angiogenenic processes through VEGFA regulation. Potential miR-195-5p targets were investigated through bioinformatic predictions and miRNA Target RNA immunoprecipitation. VEGFA expression was evaluated in public CRC datasets and paired tumor/adjacent tissues of a cohort of CRC patients by quantitative real-time PCR and immunohistochemistry. miR-195-5p gain- and loss-of-function experiments were performed in CRC cells to assess VEGFA and VEGFR2 expression and extracellular VEGF-A levels by ELISA. Endothelial tube formation assays using HUVECs were conducted to evaluate paracrine angiogenic effects. VEGFA expression was also analyzed in an AOM/DSS-induced murine CRC model treated with a miR-195-5p mimic. VEGFA was predicted as a conserved miR-195-5p target and was enriched in miR-195-5p-associated RISCs. VEGFA was overexpressed in CRC tissues compared to normal or adjacent non-tumor tissues. miR-195-5p restoration reduced VEGFA mRNA and protein expression, extracellular VEGF-A levels, and VEGFR2 protein levels in the HCT116 CRC cell line, whereas miR-195-5p inhibition produced the opposite molecular profile. Conditioned media from miR-195-5p-overexpressing CRC cells significantly impaired endothelial tube formation. Consistently, miR-195-5p in vivo administration reduced colonic Vegfa expression in AOM/DSS-treated mice. Overall, these findings indicate that miR-195-5p negatively modulates VEGFA expression and reduces the ability of CRC cell-derived conditioned media to support endothelial tube formation. This study extends the tumor-suppressive functions previously attributed to miR-195-5p by supporting its involvement in the regulation of angiogenesis-related processes in CRC.
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BibTeX
@article{piccinno2026mir1955p,
title = {{miR-195-5p Reduces VEGFA Expression and Angiogenesis in Colorectal Cancer}},
author = {Emanuele Piccinno and Viviana Scalavino and Giusy Bianco and Serena Mancarella and Ilaria Grassi and Maria Teresa Savino and Raffaele Armentano and Gianluigi Giannelli and Grazia Serino},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219971},
url = {https://www.mdpi.com/1422-0067/27/21/9971},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - miR-195-5p Reduces VEGFA Expression and Angiogenesis in Colorectal Cancer
AU - Emanuele Piccinno
AU - Viviana Scalavino
AU - Giusy Bianco
AU - Serena Mancarella
AU - Ilaria Grassi
AU - Maria Teresa Savino
AU - Raffaele Armentano
AU - Gianluigi Giannelli
AU - Grazia Serino
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219971
UR - https://www.mdpi.com/1422-0067/27/21/9971
AB - Angiogenesis is a key process in colorectal cancer (CRC) progression, with vascular endothelial growth factor A (VEGFA) being a major pro-angiogenic mediator. miR-195-5p has previously been identified by our group as a tumor-suppressive miRNA downregulated in CRC. Here, we aimed to investigate whether miR-195-5p contributes to CRC-associated angiogenenic processes through VEGFA regulation. Potential miR-195-5p targets were investigated through bioinformatic predictions and miRNA Target RNA immunoprecipitation. VEGFA expression was evaluated in public CRC datasets and paired tumor/adjacent tissues of a cohort of CRC patients by quantitative real-time PCR and immunohistochemistry. miR-195-5p gain- and loss-of-function experiments were performed in CRC cells to assess VEGFA and VEGFR2 expression and extracellular VEGF-A levels by ELISA. Endothelial tube formation assays using HUVECs were conducted to evaluate paracrine angiogenic effects. VEGFA expression was also analyzed in an AOM/DSS-induced murine CRC model treated with a miR-195-5p mimic. VEGFA was predicted as a conserved miR-195-5p target and was enriched in miR-195-5p-associated RISCs. VEGFA was overexpressed in CRC tissues compared to normal or adjacent non-tumor tissues. miR-195-5p restoration reduced VEGFA mRNA and protein expression, extracellular VEGF-A levels, and VEGFR2 protein levels in the HCT116 CRC cell line, whereas miR-195-5p inhibition produced the opposite molecular profile. Conditioned media from miR-195-5p-overexpressing CRC cells significantly impaired endothelial tube formation. Consistently, miR-195-5p in vivo administration reduced colonic Vegfa expression in AOM/DSS-treated mice. Overall, these findings indicate that miR-195-5p negatively modulates VEGFA expression and reduces the ability of CRC cell-derived conditioned media to support endothelial tube formation. This study extends the tumor-suppressive functions previously attributed to miR-195-5p by supporting its involvement in the regulation of angiogenesis-related processes in CRC.
SN - 1422-0067
ER -