biostudies-literatureHuang LNational Natural Science Foundation of ChinaNatural Science Foundation of Guangdong Province103https://www.ebi.ac.uk/biostudies/studies/S-EPMC11929334biostudies-literatureUnknown44(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Result</h4>We repoJournal of experimental & clinical cancer research : CRN&lt;sup&gt;4&lt;/sup&gt;-acetylcytidine modification of ITGB5 mRNA mediated by NAT10 promotes perineural invasion in pancreatic ductal adenocarcinoma.PMC11929334820731492022A151522021982472893Liu JLi JZhou QLu YGuo XFu ZHuang LZhou YHe RChen RZhou JfalseN&lt;sup&gt;4&lt;/sup&gt;-acetylcytidine modification of ITGB5 mRNA mediated by NAT10 promotes perineural invasion in pancreatic ductal adenocarcinoma.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Result</h4>We repo2025-01-01T00:00:00Z2025 Mar2026-06-01T22:57:17.246Z2025-07-04T03:06:02.629ZS-EPMC119293344011935310.1186/s13046-025-03362-2