Insulin-like growth factor 2 mRNA binding protein 2 regulates proliferation, migration, and angiogenesis of keratinocytes by modulating heparanase stability

Abstract

Wound healing is related to proliferation, migration, and angiogenesis of keratinocytes. Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is an important N6-methyladenosine (m6A) reader, which is involved in multiple processes, including wound healing. However, the function and mechanism of IGF2BP2 in keratinocyte processes are largely uncertain. In the present study, expression levels of IGF2BP2 and heparanase (HPSE) were detected by quantitative reverse transcription polymerase chain reaction and western blotting assays. Cell proliferation was investigated by cell counting kit-8 (CCK-8) analysis. Cell migration was determined through wound healing assay. Angiogenesis was measured by tube formation assay and vascular endothelial growth factor (VEGF) level using enzyme linked immunosorbent assay (ELISA). The interaction between IGF2BP2 and HPSE was analyzed by RNA immunoprecipitation, pull-down and luciferase reporter analyses. The results showed that IGF2BP2 expression was enhanced in wound healing. IGF2BP2 downregulation constrained HaCaT cell proliferation, migration, and angiogenesis. IGF2BP2 knockdown decreased HPSE expression. IGF2BP2 could regulate HPSE stability by binding with 3ʹ untranslated region (UTR) of HPSE. HPSE upregulation attenuated silencing IGF2BP2-mediated suppression of proliferation, migration, and angiogenesis. As a conclusion, IGF2BP2 knockdown repressed proliferation, migration, and angiogenesis of HaCaT cells by decreasing HPSE stability.

Effect of Azelaic Acid on Psoriasis Progression Investigated Based on Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Signaling Pathway

“…Previous studies have found that decreased VEGF secretion in HaCaT inhibits angiogenesis. 33 , 34 Eunah Suhng et al found that LL-37 and IL-33 enhanced VEGF mRNA expression and VEGF release in HaCaT cells. Thus, IL-33 and LL-37 may mediate the angiogenesis of rosacea skin through VEGF.…”

Cancer susceptibility 18 positively regulates NUAK Family Kinase 1 expression to promote migration and invasion via sponging of miR-5586-5p in cervical cancer cells

“…Cell migration was investigated by wound healing assay according to protocols as reported previously. 27 A sterile 200 µl pipette tip was used to scrape an injured area on the monolayer in a six-well culture dish when the cells reached 80% confluence. The culture was continued in a medium supplemented with 3% FBS and 1% penicillin/streptomycin (TransGen, Beijing, China).…”

Competitive endogenous RNA networks: Decoding the role of long non‐coding RNAs and circular RNAs in colorectal cancer chemoresistance

“…The subgroups of the insulin‐like growth factor‐2 mRNA‐binding protein (IGF2BP) family play critical roles in embryogenesis, carcinogenesis, and chemoresistance by influencing the stability, translatability, or location of ncRNAs 96–98 . Specifically, IGF2BP2 has been identified as a pro‐tumour factor in various solid tumours 99 .…”

“…The subgroups of the insulin‐like growth factor‐2 mRNA‐binding protein (IGF2BP) family play critical roles in embryogenesis, carcinogenesis, and chemoresistance by influencing the stability, translatability, or location of ncRNAs. 96 , 97 , 98 Specifically, IGF2BP2 has been identified as a pro‐tumour factor in various solid tumours. 99 In a recent study by Xia et al., 100 it was found that IGF2BP2 levels are elevated in CRC cells and tissues compared to normal counterparts.…”