HNRNPF Increases MAF and CCNB2 Levels To Promote Cancer Cell Stemness and Progression of Pancreatic Ductal Adenocarcinoma

BACKGROUND: Tumor stemness, the capacity of a subset of Cancer cells to self‑renew and drive tumor growth, has been implicated in pancreatic ductal adenocarcinoma (PDAC) aggressiveness. Heterogeneous nuclear ribonucleoprotein F (HNRNPF) is an RNA‑binding protein involved in mRNA processing, but its role in regulating stemness in PDAC remains unclear. This paper investigates the impact of HNRNPF on tumor stemness by regulating musculoaponeurotic fibrosarcoma (MAF) stability and cyclin B2 (CCNB2) transcription in PDAC. METHODS: The expression of HNRNPF, MAF, and CCNB2 in tumor and paracancerous tissues of PDAC patients was detected. The proliferative and invasive potential of PDAC was examined in vitro and in vivo after lentiviral intervention. A sphere formation assay was performed to analyze the self-renewal capacity of PDAC cells, and the expression of tumor stemness markers was detected. ChIP-qPCR and dual-luciferase assays were conducted to explore the transcriptional regulation between MAF and CCNB2. RNA immunoprecipitation and RNA decay assays were used to examine the regulation of HNRNPF on MAF. RESULTS: HNRNPF, MAF, and CCNB2 were highly expressed in tumor tissues of PDAC patients. The transcription factor MAF was enriched in the CCNB2 promoter to activate its expression. HNRNPF stabilized MAF mRNA and upregulated MAF mRNA expression. Knockdown of either MAF or HNRNPF significantly inhibited PDAC progression and self-renewal ability, whereas combined CCNB2 or MAF overexpression reversed this trend. CONCLUSION: Overexpression of HNRNPF in PDAC stabilizes MAF to transcriptionally activate CCNB2, thereby enhancing tumor stemness and promoting PDAC malignancy.

CCNB2; HNRNPF; MAF; Pancreatic ductal adenocarcinoma; Stemness.