VEGFR3 suppression through miR-1236 inhibits proliferation and induces apoptosis in ovarian cancer via ERK1/2 and AKT signaling pathways.

Abstract

Vascular endothelial growth factor receptor 3 (VEGFR3) is expressed in cancer cell lines and exerts a critical role in cancer progression. However, the signaling pathways of VEGFR3 in ovarian cancer cell proliferation remain unclear. This study aimed to demonstrate the signaling pathways of VEGFR3 through the upregulated expression of miR-1236 in ovarian cancer cells. We found that the messenger RNA and protein of VEGFR3 were expressed in the ovarian cancer cell lines, but downregulated after microRNA-1236 (miR-1236) transfection. The inhibition of VEGFR3, using miR-1236, significantly reduced cell proliferation, clonogenic survival, migration, and invasion ability in SKOV3 and OVCAR3 cells (p < 0.01). The flow cytometry results indicated that the rate of apoptotic cells in SKOV3 (38.65%) and OVCAR3 (41.95%) cells increased following VEGFR3 inhibition. Moreover, VEGFR3 stimulation (using a specific ligand, VEGF-CS) significantly increased extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation (p < 0.01), whereas VEGFR3 suppression reduced p-ERK1/2 (67.94% in SKOV3 and 93.52% in OVCAR3) and p-AKT (59.56% in SKOV3 and 78.73% in OVCAR3) compared to the VEGF-CS treated group. This finding demonstrated that miR-1236 may act as an endogenous regulator of ERK1/2 and AKT signaling by blocking the upstream regulator of VEGFR3. Overall, we demonstrated the important role of the miR-1236/VEGFR3 axis in ovarian cancer cell proliferation by regulating the ERK1/2 and AKT signaling that might be an effective strategy against ovarian cancer.

• Authors: Zeinab Babaei, Mojtaba Panjehpour, Seyedeh Sara Ghorbanhosseini, Hadi Parsian, Mahsa Khademi, Mahmoud Aghaei
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 124 Issue 5 Pg. 674-686 (05 2023) ISSN: 1097-4644 [Electronic] United States
• PMID: 36922713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Wiley Periodicals LLC.

Chemical References

• MicroRNAs
• MIRN1236 microRNA, human
• Mitogen-Activated Protein Kinase 3
• Proto-Oncogene Proteins c-akt
• Vascular Endothelial Growth Factor Receptor-3

Topics

• Female
• Humans
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• MAP Kinase Signaling System
• MicroRNAs (metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Ovarian Neoplasms (genetics)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction (genetics)
• Vascular Endothelial Growth Factor Receptor-3 (genetics, metabolism, pharmacology)