PMID- 35526050
OWN - NLM
STAT- MEDLINE
DCOM- 20220510
LR  - 20240102
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 15
IP  - 1
DP  - 2022 May 7
TI  - LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and 
      m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma.
PG  - 52
LID - 10.1186/s13045-022-01272-w [doi]
LID - 52
AB  - 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.
CI  - (c) 2022. The Author(s).
FAU - Liu, Yihao
AU  - Liu Y
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Department of Zoology, College of Life Science, Nankai University, Tianjin, 
      300071, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Shi, Minmin
AU  - Shi M
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - He, Xingfeng
AU  - He X
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Cao, Yizhi
AU  - Cao Y
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Liu, Pengyi
AU  - Liu P
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Li, Fanlu
AU  - Li F
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Zou, Siyi
AU  - Zou S
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Wen, Chenlei
AU  - Wen C
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Zhan, Qian
AU  - Zhan Q
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Xu, Zhiwei
AU  - Xu Z
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Wang, Jiancheng
AU  - Wang J
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China. wjc10585@rjh.com.cn.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China. wjc10585@rjh.com.cn.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China. 
      wjc10585@rjh.com.cn.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China. wjc10585@rjh.com.cn.
FAU - Sun, Baofa
AU  - Sun B
AD  - Department of Zoology, College of Life Science, Nankai University, Tianjin, 
      300071, China. sunbf@nankai.edu.cn.
FAU - Shen, Baiyong
AU  - Shen B
AD  - Department of General Surgery, Pancreatic Disease Center, Research Institute of 
      Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China. shenby@shsmu.edu.cn.
AD  - Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of 
      Medicine, Shanghai, 200025, China. shenby@shsmu.edu.cn.
AD  - State Key Laboratory of Oncogenes and Related Genes, Institute of Translational 
      Medicine, Shanghai Jiaotong University, Shanghai, 200025, China. 
      shenby@shsmu.edu.cn.
AD  - Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, 
      China. shenby@shsmu.edu.cn.
LA  - eng
GR  - 81871906/National Natural Science Foundation/
GR  - 82073326/National Natural Science Foundation of 799 China/
GR  - ZH2018ZDA01/Medical-Engineering Cross Foundation of Shanghai Jiao Tong 
      University/
GR  - TM201903/Shanghai Collaborative Innovation Center for Translational Medicine/
PT  - Journal Article
DEP - 20220507
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (IGF2BP2 protein, human)
RN  - 0 (KLF12 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (MIRN671 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - *Carcinoma, Pancreatic Ductal/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Kruppel-Like Transcription Factors/genetics
MH  - Macrophages/metabolism
MH  - *MicroRNAs/genetics
MH  - *Pancreatic Neoplasms/pathology
MH  - *RNA, Long Noncoding/genetics
MH  - *RNA-Binding Proteins/genetics
MH  - Tumor Microenvironment
PMC - PMC9077921
OTO - NOTNLM
OT  - IGF2BP2
OT  - KLF12
OT  - LncRNA-PACERR
OT  - PDAC
OT  - TAMs
OT  - m6A
OT  - miR-671-3p
COIS- The authors declare that they have no competing interests.
EDAT- 2022/05/08 06:00
MHDA- 2022/05/11 06:00
PMCR- 2022/05/07
CRDT- 2022/05/07 23:40
PHST- 2022/01/20 00:00 [received]
PHST- 2022/04/21 00:00 [accepted]
PHST- 2022/05/07 23:40 [entrez]
PHST- 2022/05/08 06:00 [pubmed]
PHST- 2022/05/11 06:00 [medline]
PHST- 2022/05/07 00:00 [pmc-release]
AID - 10.1186/s13045-022-01272-w [pii]
AID - 1272 [pii]
AID - 10.1186/s13045-022-01272-w [doi]
PST - epublish
SO  - J Hematol Oncol. 2022 May 7;15(1):52. doi: 10.1186/s13045-022-01272-w.