Pancreatic ductal adenocarcinoma cells regulated the gemcitabine‐resistance function of CAFs by LINC00460. Issue 11 (15th September 2022)

• Record Type: Journal Article
• Authors: Zhu, Xiao‐Xu; Li, Jian‐Hui; Ni, Xuhao; Wu, Xiao; Hou, Xun; Li, Ya‐Xiong; Li, Shi‐Jin; Zhao, Wei; Yin, Xiao‐Yu
• Is Part Of: Cancer science. Volume 113:Issue 11(2022)
• Page Start: 3735
• Page End: 3750
• Publication Date: 2022-09-15
• Subjects: cancer associated fibroblasts -- gemcitabine‐resistance -- LINC00460 -- pancreatic ductal adenocarcinoma -- PDAP1; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15547
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC‐PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull‐down, LC–MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine‐resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC‐PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460. Abstract : LINC00460 regulates the gemcitabine chemotherapy‐resistance function of CAFs via the PDAP1/PDGFA/PDGFR pathway, which could be attenuated by treatment with a PDGFR inhibitor (crenolanib).PDAC with low expressed LINC00460 is an indicator to apply treatment therapy of gemcitabine combine with crenolanib.