FOXA2-initiated transcriptional activation of INHBA induced by methylmalonic acid promotes pancreatic neuroendocrine neoplasm progression

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Introduction: More than 60% of pancreatic neuroendocrine neoplasms (PanNENs) represent metastases when diagnosed. Metabolic alterations have been recognized as one of the hallmarks of tumor metastasis. However, little is known about the molecular mechanism of metabolic changes regulating PanNEN progression.

Aim(s): To identify the differential metabolites correlating with PanNEN metastasis based on serum metabolomics, and clarify the specific molecular mechanism.

Materials and methods: Targeted Metabolomics was performed to analyze the differential metabolites between metastatic and non-metastatic PanNENs. RNA sequencing was conducted to explore the potential mechanisms. ChIP and dual luciferase reporter assays were used to confirm the transcription factor binding to the INHBA promoter region. The function of MMA in vivo was determined by subcutaneous tumorigenesis and metastatic tumor models.

Conference:

Presenting Author:

Authors: Hu C,

Keywords: metabolic alteration, tumor progression, pancreatic neuroendocrine neoplasm, FOXA2, INHBA, epithelial-mesenchymal transition,