ArticleIn vitro cellular & developmental biology. Animal2026
E3 ubiquitin ligase SYVN1 promotes the malignant phenotype of A549 cells by upregulating GATA3 expression via NRP1.
Article in In vitro cellular & developmental biology. Animal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Lung cancer remains one of the most lethal and prevalent malignancies worldwide. Although E3 ubiquitin ligase SYVN1 is frequently amplified in lung cancer, its functional role has not been fully elucidated. This study investigates the mechanistic involvement of SYVN1 in regulating the GATA3/NRP1 axis in A549 cells to provide novel insights into potential therapeutic strategies for lung cancer. Expression levels of SYVN1 were assessed in BEAS-2B, A549, NCI-H647, NCI-H2170, and NCI-H520, NCI-H69 cells. Functional assays were conducted after overexpressing or silencing SYVN1, GATA3, and/or NRP1 in A549 cells to examine their interdependent roles. The cells' proliferation, wound healing, invasion and migration abilities were evaluated through CCK-8, scratch assay and Transwell assays, respectively. The results indicated that SYVN1 was upregulated in A549 cells and significantly promoted cell proliferation, invasion, and migration. Mechanistically, SYVN1 interacted with GATA3 and regulated its ubiquitination. Knockdown of SYVN1 suppressed A549 cell proliferation, wound healing, invasion, and migration, and these effects could be reversed by overexpressing GATA3. Similarly, silencing GATA3 reduced these malignant characteristics, but these effects could be restored by overexpressing NRP1, and the knockdown of NRP1 could abrogate the tumor-promoting effects of SYVN1 overexpression. SYVN1 overexpression counteracted the inhibitory effects of NRP1 silencing on A549 tumor progression. Taken together, all these findings prove that SYVN1 could promote the malignant characteristics of A549 cells by modulating the GATA3/NRP1 axis. Thus, targeting SYVN1 could represent a promising therapeutic approach for treating lung cancer.
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