MicroRNA‑203a‑3p suppresses endothelial cell proliferation and invasion, and promotes apoptosis in hemangioma by inactivating the VEGF‑mediated PI3K/AKT pathway

Abstract

Our previous study demonstrated that was involved in the regulation of long non-coding RNA MEG8-mediated the progression of hemangioma, which is a benign tumor characterized by endothelial hyperplasia in the blood vessels and primarily occurring in infants and females. Therefore, the present study aimed to further investigate the effects of miR-203a-3p on endothelial cell proliferation, invasion and apoptosis, as well as its underlying mechanism in hemangioma. Human hemangioma endothelial cells (HemECs) were first transfected with either miR-203a-3p mimics or a miR-203a-3p inhibitor. Subsequently, vascular endothelial growth factor A (VEGFA) was overexpressed in these cells. Cell proliferation (by Cell Counting Kit-8 assay), apoptosis (by TUNEL assay), invasion (by Transwell assay) and PI3K/AKT signaling (by western blot) were assessed following transfection of these cells. Notably, transfection with miR-203a-3p mimics caused a reduction in cell proliferation, invasion and in the phosphorylation levels of PI3K and AKT, and promoted cell apoptosis in HemECs. By contrast, transfection with the miR-203a-3p inhibitor exerted the opposite effects compared with those of the miR-203a-3p mimics. miR-203a-3p was revealed to directly suppress VEGFA expression in HemECs. VEGFA overexpression alone increased cell proliferation and invasion, but decreased apoptosis. Furthermore, VEGFA co-transfection reversed the effects mediated by miR-203a-3p mimics transfection in HemECs. Mechanistically, miR-203a-3p was demonstrated to inactivate the PI3K/AKT pathway, whereas VEGFA overexpression produced the opposite effect. VEGFA co-transfection also attenuated the miR-203a-3p mimics-induced inactivation of PI3K/AKT signaling in HemECs. In conclusion, these data suggested that miR-203a-3p may inhibit endothelial cell proliferation and invasion, and promote apoptosis by inactivating VEGFA and PI3K/AKT signaling in hemangioma. These findings also implicated miR-203 as a possible treatment option for this disease.

MicroRNA‑203a‑3p improves bleomycin and pingyangmycin sensitivity by inactivating the PI3K/AKT pathway in hemangioma

“…Our previous study reported that miR-203a-3p inhibits the PI3K/AKT pathway to facilitate hemangioma progression ( 24 ). Therefore, the effect of 740 Y-P, an activator of PI3K, was analyzed in the present study.…”

“…Following transfection, HemECs were collected for detection of miR-203a-3p expression with RT-qPCR as previously described ( 24 ). In brief, total RNA was isolated using the RNeasy Mini kit (Qiagen GmbH).…”

“…miR-203a-3p silencing regulates the long non-coding RNA maternally expressed 8-mediated Notch pathway to increase hemangioma cell proliferation and invasion whilst decreasing apoptosis ( 23 ). Furthermore, miR-203a-3p overexpression inactivates vascular endothelial growth factor A (VEGFA)-regulated PI3K/AKT pathway signaling to inhibit hemangioma cell proliferation and invasion, as well as increase apoptosis ( 24 ). A number of studies have reported the involvement of the PI3K/AKT pathway in sensitizing hemangioma cells to BLM and PYM ( 25 , 26 ).…”

Mechanism of the HIF‐1α/VEGF/VEGFR‐2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells

“…Overexpression of VEGFA alone promotes the invasion and proliferation of HemECs but reduces apoptosis. 37 Deletion of VEGF can abolish IL-6-induced HA progression. 38 VEGF induces VEGFdependent activation of VEGFR2 to facilitate HemEC growth.…”

“…Furthermore, we conducted functional rescue assays by silencing HIF‐1α and introducing pcDNA3.1 VEGF into HemECs simultaneously and elaborated that overexpression of VEGF decreased HemECs arrest at the G0/G1 phase, repressed the apoptosis, and facilitated the viability, proliferation, invasion, migration, and tubular formation of HemECs. Overexpression of VEGFA alone promotes the invasion and proliferation of HemECs but reduces apoptosis 37 . Deletion of VEGF can abolish IL‐6‐induced HA progression 38 .…”