CSTF2T facilitates pancreatic adenocarcinoma growth and metastasis by elevating H3K4Me1 methylation of CALB2 via ASH2L.

Pancreatic adenocarcinoma (PAAD) is a major cause of mortality related to cancer worldwide. This paper dissected the functions of the CSTF2T/ASH2L/CALB2 axis in PAAD progression. CALB2 expression was assessed in PAAD tissues and cells using RT-qPCR and western blot. Subsequent to gain- and loss-of-function experiments in PAAD cells, cell apoptosis, invasion, proliferation, and migration were examined using flow cytometry, Transwell, CCK-8, and Scratch assays. Additionally, the expression of proliferation markers and apoptotic and metastasis- and invasion-related proteins was measured using western blot. The relationship among CALB2, KMT2D, ASH2L, H3K4Me1, and CSTF2T was evaluated using ChIP, RNA pull-down, RIP, and Co-IP assays. A nude mouse transplantation tumor model was established, with observation of tumor growth and metastasis. CALB2 expression was high in PAAD tissues and cells. Mechanistically, KMT2D was enriched in the CALB2 promoter, and CSTF2T bound to and upregulated ASH2L as a RNA binding protein, which was a core component of the KMT2D complex to enhance CALB2 expression through H3K4Me1 upregulation. CALB2 knockdown diminished the viability, invasion, and migration but elevated the apoptosis of PAAD cells. Likewise, CSTF2T knockdown suppressed the growth and metastasis of PAAD cells and transplanted tumors in nude mice, which was counteracted by further CALB2 overexpression. CSTF2T knockdown blocked the ASH2L/CALB2 axis to protect against PAAD growth and metastasis.