Abstract
Novel therapeutic targets and their inhibitors for esophageal squamous cell carcinoma (ESCC) prevention and therapy are urgently needed. This study aimed to investigate the function of DEAD-box helicase 5 (DDX5) in ESCC progression and to identify a promising inhibitor of DDX5. We verified that DDX5 was highly expressed in ESCC and played an oncogenic role, binding with vav guanine nucleotide exchange factor 3 (VAV3) mRNA and facilitating VAV3 mRNA N6-methyladenosine (m6A) modification by interacting with the m6A methyltransferase 3 (METTL3). M6A-modified VAV3 mRNA was identified by insulin-like growth factor 1 (IGF2BP1), increasing mRNA stability. Methylnissolin-3-β-D-O-glucoside (MD) inhibited ESCC progression through the DDX5-VAV3 axis. Our findings suggest that DDX5 promotes ESCC progression. MD inhibits ESCC progression by targeting DDX5.
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
MeSH terms
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Adenosine / analogs & derivatives
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Adenosine / metabolism
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Animals
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Cell Line, Tumor
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Cell Proliferation / genetics
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DEAD-box RNA Helicases* / genetics
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DEAD-box RNA Helicases* / metabolism
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Disease Progression
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Esophageal Neoplasms* / genetics
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Esophageal Neoplasms* / metabolism
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Esophageal Neoplasms* / pathology
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Esophageal Squamous Cell Carcinoma* / genetics
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Esophageal Squamous Cell Carcinoma* / metabolism
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Esophageal Squamous Cell Carcinoma* / pathology
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Male
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Methyltransferases / genetics
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Methyltransferases / metabolism
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Mice
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Mice, Nude
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Proto-Oncogene Proteins c-vav* / genetics
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Proto-Oncogene Proteins c-vav* / metabolism
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RNA Stability* / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
Substances
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DEAD-box RNA Helicases
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Proto-Oncogene Proteins c-vav
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Ddx5 protein, human
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VAV3 protein, human
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Methyltransferases
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METTL3 protein, human
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RNA, Messenger
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Adenosine