MiR-128-3p directly targets VEGFC/VEGFR3 to modulate the proliferation of lymphatic endothelial cells through Ca2+ signaling

The International Journal of Biochemistry & Cell Biology
Jie ZhouXiaoyuan Huang

Abstract

Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation. By using online tools, miR-128 and miR-3916 were predicted as candidate upstream miRNAs which might target VEGFC/VEGFR3. As verified using Immunoblotting assays, miR-128 significantly regulated the protein levels of VEGFC/VEGFR3, whereas miR-3916 only slightly modulated VEGFC and VEGFR3 proteins. Contrary to VEGFC, miR-128 overexpression remarkably suppressed LEC proliferation, Ca2+ release and ERK1/2-Akt signaling; moreover, the effect of VEGFC could be partially attenuated by miR-128. In summary, miR-128 interacts with the 3'-UTR of VEGFC and VEGFR3 to inhibit their expression, thus suppressing LEC proliferation through Ca2+ and ERK1/2-Akt signaling. Taken together, we provided...Continue Reading

Citations

Apr 30, 2020·Journal of Clinical Medicine·Daniel P ZalewskiAnna Bogucka-Kocka
Nov 27, 2020·Journal of Cellular Physiology·Qi ShangHui Ren
May 26, 2020·Mechanisms of Ageing and Development·Xingjie MaWeili Liu
Nov 12, 2020·Cancers·Khairunnisa' Md YusofKelly A Avery-Kiejda
Mar 27, 2021·Frontiers in Oncology·Chiara BresestiMarco Bonomi

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