Background: Polypyrimidine tract binding protein 1 (PTBP1) plays a crucial role in the stemness of various cancer types. Therefore, this study aimed to unveil the potential role of PTBP1 in the metastatic progression of pancreatic cancer (PC).

Methods: PTBP1 expression was confirmed in PC using bioinformatics analysis and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) data. After correlation analysis, RNA immunoprecipitation assay was employed to assess the interaction between PTBP1 and homeobox A9 (HOXA9). Based on the gain- or loss-of-function of the gene, the impact of PTBP1 in PC cells and its underlying regulatory mechanism in malignant behavior were investigated using a cell counting kit-8 (CCK-8) assay, flow cytometry, a Transwell assay and Western blot analysis.

Results: PTBP1 was found to be upregulated in PC. PTBP1 silencing enhanced cell apoptosis and dysregulated cell viability, migration, and invasion. PTBP1 silencing repressed epithelial-mesenchymal transition (EMT) by upregulating epithelial cadherin (E-cadherin) and downregulating neural cadherin (N-cadherin), Vimentin, and Snail. However, these effects were reversed by the overexpression of HOXA9. PTBP1–HOXA9 interaction upregulated HOXA9 expression. Furthermore, HOXA9 overexpression reduced apoptosis and enhanced viability, migration, invasion, and EMT in PC cells. However, these effects were counteracted by the knockdown of PTBP1.

Conclusions: PTBP1 drives EMT and promotes PC cell survival, migration, and invasion through interacting and upregulating HOXA9 expression.