Neoplasma Vol.71, No.1, p. 22–36, 2024
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| Title: The role of HMGA2 in activating the IGFBP2 expression to promote angiogenesis and LUAD metastasis via the PI3K/AKT/VEGFA signaling pathway |
| Author: Shuai Qian, Fengping Wang, Wenliang Liao, Jun Liu |
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Abstract: This study investigates the molecular mechanism of HMGA2-mediated regulation of IGFBP2 expression in the PI3K/AKT/VEGFA signaling pathway, which is involved in angiogenesis and LUAD metastasis. Target genes with prognostic implications for LUAD patients were selected using bioinformatics, and previously published literature was referenced to predict the molecular regulatory mechanisms. A549 cells were used for in vitro validation. Cell proliferation and viability were assessed using CCK-8 and EdU assays, while cell migration ability was evaluated using Transwell and wound healing assays. Changes in angiogenesis were examined using an angiogenesis assay. The targeted binding of HMGA2 with the IGFBP2 promoter was confirmed through dual luciferase reporter gene experiments and ChIP assays. In vivo validation was performed using a xenograft mouse model, and changes in angiogenesis and tumor metastasis were observed using western blot, immunofluorescence, and H&E staining. Bioinformatics analysis revealed that HMGA2 was one of the AAGs that differed between normal individuals and LUAD patients, and could serve as a critical mRNA for predicting LUAD prognosis. Results from in vitro experiments demonstrated that the expression of the HMGA2 gene was significantly upregulated in LUAD cell lines. Through mediating the expression of IGFBP2, the HMGA2 gene activated the PI3K/AKT/VEGFA signaling pathway, promoting the proliferation, migration, and angiogenesis of A549 cells. In vivo, animal experiments further confirmed that HMGA2 facilitated angiogenesis and the development and metastasis of LUAD through mediating IGFBP2 expression and activating the PI3K/AKT/VEGFA signaling pathway. HMGA2 promotes angiogenesis and healthy growth and metastasis of LUAD by activating the PI3K/AKT/VEGFA signaling pathway by mediating IGFBP2 expression.
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| Keywords: HMGA2; IGFBP2; PI3K/AKT/VEGFA signaling pathway; angiogenesis; LUAD metastasis; bioinformatics; A549 cells; xenograft mouse model |
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Published online: 23-Jan-2024
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| Year: 2024, Volume: 71, Issue: 1 |
Page From: 22, Page To: 36 |
doi:10.4149/neo_2024_230907N476
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