Pracinostat inhibits the nefarious biological behavior of pancreatic cancer by targeting the miR-381-3p/MDM2 axis to activate the p53 signaling pathway

Objective: Pancreatic Cancer is one of the most aggressive malignant tumors in humans, with poor prognosis. The acetylase tumor inhibitor (Pracinostat) has been shown to suppress the growth of various tumors. This study aimed to investigate the effects of Pracinostat on the pancreatic Cancer cell line BxPC3 and to explore the underlying molecular mechanisms through both in vivo and in vitro experiments.

Methods: BxPC3 cells were treated with Pracinostat, and cell viability was assessed by CCK-8 assay; the differentially expressed miRNAs in cells before and after pracinostat treatment were screened by high-throughput Sequencing, and miR-381-3p was selected as the target gene; the targeting relationship between miR-381-3p and MDM2 was verified by double luciferase reporter gene; the relationship between miR-381-3p, MDM2 and P53 signaling pathways was verified by immunoprecipitation, Western blot and Other experiments. Pancreatic tumor models were established in BALB/c nude mice to study the role of pracinostat in vivo.

Results: Pracinostat upregulated the expression of miR-381-3p and p53, while downregulating MDM2 expression. It also inhibited the proliferation and migration of pancreatic Cancer cells and promoted Apoptosis. Treatment with a miR-381-3p inhibitor reversed the effects of Pracinostat. In addition, MDM2 was found to promote the ubiquitination and degradation of p53 via the ubiquitin-proteasome pathway. In vivo experiments confirmed that Pracinostat inhibited tumor growth in nude mice.

Conclusion: pracinostat activates the p53 signaling pathway by targeting the miR-381-3p/MDM2 axis, thereby inhibiting the proliferation of pancreatic Cancer cells. These findings provide novel insights and potential therapeutic strategies for pancreatic Cancer, and may also provide a reference for the treatment of Other malignancies.

Degradation of p53 ubiquitination; MDM2; MiR-381–3p; Pancreatic cancer; Pracinostat.