N⁴-acetylcytidine modification of ITGB5 mRNA mediated by NAT10 promotes perineural invasion in pancreatic ductal adenocarcinoma.

ABSTRACT:

Background

Perineural invasion (PNI) is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC), which occurs at a high incidence and significantly contributes to PDAC lethality and poor survival. Despite its prevalence and association with poor prognosis, the molecular mechanisms underlying PNI in PDAC remain unclear.

Methods

We investigated clinical samples from two cohorts by UPLC/MS-MS to profiled significantly altered chemical RNA modifications in PDAC tissues with PNI lesions. Dorsal root ganglion coculture systems and sciatic nerve injection models validated PNI ability. We combined RNA-seq, acRIP-seq and ac4C-seq with CRISPR-based techniques to explore the regulatory mechanism of ac4C modification on the integrin beta 5 (ITGB5) transcript.

Result

We repo

SUBMITTER: Huang L 

PROVIDER: S-EPMC11929334 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature