NEAT1 promotes the perineural invasion of pancreatic cancer via the E2F1/GDNF axis

Abstract

Pancreatic cancer is characterized by an insidious onset and high degree of malignancy, with a 5-year survival rate of less than 11 %. Perineural invasion (PNI) is one of the pathological features of pancreatic cancer and provides a pathway for distant tumor metastasis, which leads to a poor prognosis. Although NEAT1 promotes the progression of pancreatic cancer, its impact on PNI has not been studied. In this study, we found that NEAT1 facilitates pancreatic cancer metastasis and PNI by regulating E2F1. In vivo experiments showed that NEAT1 promotes PNI in a mouse model. Furthermore, E2F1 is enriched at the promoter region of GDNF and directly participates in its transcriptional regulation. NEAT1 can also recruit P300 to the GDNF promoter region, thereby inducing the H3K27ac modification to further increase chromatin accessibility. This process ultimately facilitates GDNF transcription and tumor innervation, providing a pathway for tumor metastasis.

Keywords: GDNF; Histone modification; LncRNA; P300; Perineural invasion.