Author:
Liu Yihao,Shi Minmin,He Xingfeng,Cao Yizhi,Liu Pengyi,Li Fanlu,Zou Siyi,Wen Chenlei,Zhan Qian,Xu Zhiwei,Wang Jiancheng,Sun Baofa,Shen Baiyong
Abstract
Abstract
Background
LncRNA-PACERR plays critical role in the polarization of tissue-associated macrophages (TAMs). In this study, we found the function and molecular mechanism of PACERR in TAMs to regulate pancreatic ductal adenocarcinoma (PDAC) progression.
Methods
We used qPCR to analyse the expression of PACERR in TAMs and M1-tissue-resident macrophages (M1-NTRMs) which were isolated from 46 PDAC tissues. The function of PACERR on macrophages polarization and PDAC proliferation, migration and invasion were confirmed through in vivo and in vitro assays. The molecular mechanism of PACERR was discussed via fluorescence in situ hybridization (FISH), RNA pull-down, ChIP-qPCR, RIP-qPCR and luciferase assays.
Results
LncRNA-PACERR was high expression in TAMs and associated with poor prognosis in PDAC patients. Our finding validated that LncRNA-PACERR increased the number of M2-polarized cells and facilized cell proliferation, invasion and migration in vitro and in vivo. Mechanistically, LncRNA-PACERR activate KLF12/p-AKT/c-myc pathway by binding to miR-671-3p. And LncRNA-PACERR which bound to IGF2BP2 acts as an m6A-dependent manner to enhance the stability of KLF12 and c-myc in cytoplasm. In addition, the promoter of LncRNA-PACERR was a target of KLF12 and LncRNA-PACERR recruited EP300 to increase the acetylation of histone by interacting with KLF12 in nucleus.
Conclusions
This study found that LncRNA-PACERR functions as key regulator of TAMs in PDAC microenvironment and revealed the novel mechanisms in cytoplasm and in nucleus.
Funder
National Natural Science Foundation
National Natural Science Foundation of 799 China
Medical-Engineering Cross Foundation of Shanghai Jiao Tong University
Shanghai Collaborative Innovation Center for Translational Medicine
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Biology,Hematology
Cited by
48 articles.
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