Propranolol inhibits infantile hemangioma by regulating the miR-424/vascular endothelial growth factor-A (VEGFA) axis.

Abstract

BACKGROUND:

Infantile hemangioma (IHA) is the most common tumor in infancy. We aimed to explore the effect of propranolol on the expression of microRNA (miR)-424 in IHA tissues and XPTS-1 cells, as well as its molecular mechanism of inhibiting XPTS-1 cell activity.

METHODS:

Tumor tissues and peritumoral tissue were collected from 13 IHA patients in Lishui Municipal Central Hospital. The level of miR-424 were detected using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Cell counting kit-8 (CCK-8) was used to measure XPTS-1 cell viability. Flow cytometry and transwell were used to detect the apoptosis level and invasion ability of XPTS-1 cells. Western blot was used to measure the protein level of vascular endothelial growth factor-A (VEGFA). The luciferase reporter gene assay detected the targeting relationship between miR-424 and VEGFA.

RESULTS:

Compared with normal tissues and human umbilical vein endothelial cells, the expression level of miR-424 in IHA tissues and XPTS-1 cells was significantly reduced (P<0.05). As the concentration of propranolol increased, XPTS-1 cell viability gradually decreased (P<0.05), and the expression level of VEGFA decreased (P<0.05). The expression of miR-424 increased with the time of propranolol treatment (P<0.05). Compared with the control group, treatment with an miR-424 inhibitor resulted in a significant increase in XPTS-1 cell viability and invasion ability (P<0.05), and a decrease in apoptosis (P<0.05). However, both propranolol and miR-424 inhibitor treatment resulted in a partial decrease in XPTS-1 cell viability (P<0.05), and a partial increase in the level of apoptosis (P<0.05). MiR-424 directly targeted VEGFA; the overexpression of miR-424 resulted in a decrease in the VEGFA protein level (P<0.05), while inhibition of miR-424 resulted in an increase in the VEGFA protein level (P<0.05). Compared with the propranolol group, the XPTS-1 cell viability and invasion ability in the propranolol + VEGFA-si group were significantly decreased (P<0.05), while the level of apoptosis increased (P<0.05). Meanwhile, simultaneous miR-424 inhibitor treatment resulted in no difference in cell viability and apoptosis levels compared with the propranolol group, and the invasion ability was partially restored (P<0.05).

CONCLUSIONS:

Propranolol affects the malignant biological behavior of IHA cells by regulating the miR-424/VEGFA axis.

• Authors: Zhen-Bo Wu, Sen-Lin Shi, Feng-Jun Pan, Li Li, Hong-Yu Chen
• Journal: Translational pediatrics (Transl Pediatr) Vol. 10 Issue 7 Pg. 1867-1876 (Jul 2021) ISSN: 2224-4344 [Print] China
• PMID: 34430434 (Publication Type: Journal Article)
• Copyright: 2021 Translational Pediatrics. All rights reserved.