LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma
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 expre...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-022-01272-w |
| _version_ | 1818200873871867904 |
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| author | Yihao Liu Minmin Shi Xingfeng He Yizhi Cao Pengyi Liu Fanlu Li Siyi Zou Chenlei Wen Qian Zhan Zhiwei Xu Jiancheng Wang Baofa Sun Baiyong Shen |
| author_facet | Yihao Liu Minmin Shi Xingfeng He Yizhi Cao Pengyi Liu Fanlu Li Siyi Zou Chenlei Wen Qian Zhan Zhiwei Xu Jiancheng Wang Baofa Sun Baiyong Shen |
| author_sort | Yihao Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T02:44:35Z |
| format | Article |
| id | doaj.art-a4ba04ba4fb241959dc9fb19dbadd411 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-12T02:44:35Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-a4ba04ba4fb241959dc9fb19dbadd4112022-12-22T00:41:04ZengBMCJournal of Hematology & Oncology1756-87222022-05-0115111810.1186/s13045-022-01272-wLncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinomaYihao Liu0Minmin Shi1Xingfeng He2Yizhi Cao3Pengyi Liu4Fanlu Li5Siyi Zou6Chenlei Wen7Qian Zhan8Zhiwei Xu9Jiancheng Wang10Baofa Sun11Baiyong Shen12Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Zoology, College of Life Science, Nankai UniversityDepartment of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of MedicineAbstract 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.https://doi.org/10.1186/s13045-022-01272-wLncRNA-PACERRmiR-671-3pKLF12IGF2BP2m6ATAMs |
| spellingShingle | Yihao Liu Minmin Shi Xingfeng He Yizhi Cao Pengyi Liu Fanlu Li Siyi Zou Chenlei Wen Qian Zhan Zhiwei Xu Jiancheng Wang Baofa Sun Baiyong Shen LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma Journal of Hematology & Oncology LncRNA-PACERR miR-671-3p KLF12 IGF2BP2 m6A TAMs |
| title | LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma |
| title_full | LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma |
| title_fullStr | LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma |
| title_short | LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma |
| title_sort | lncrna pacerr induces pro tumour macrophages via interacting with mir 671 3p and m6a reader igf2bp2 in pancreatic ductal adenocarcinoma |
| topic | LncRNA-PACERR miR-671-3p KLF12 IGF2BP2 m6A TAMs |
| url | https://doi.org/10.1186/s13045-022-01272-w |
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