Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint
Abstract Background Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. Methods The tumor and adjacent normal tissues were collected from 73 PC patients. T...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-022-02741-5 |
| _version_ | 1811179144112766976 |
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| author | Jun Yao Ruoyu Gao Minghan Luo Defeng Li Liliangzi Guo Zichao Yu Feng Xiong Cheng Wei Benhua Wu Zhenglei Xu Dingguo Zhang Jianyao Wang Lisheng Wang |
| author_facet | Jun Yao Ruoyu Gao Minghan Luo Defeng Li Liliangzi Guo Zichao Yu Feng Xiong Cheng Wei Benhua Wu Zhenglei Xu Dingguo Zhang Jianyao Wang Lisheng Wang |
| author_sort | Jun Yao |
| collection | DOAJ |
| description | Abstract Background Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. Methods The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. Results LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. Conclusions LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC. |
| first_indexed | 2024-04-11T06:30:54Z |
| format | Article |
| id | doaj.art-a745b302d3a54c9b884b962e95089358 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-11T06:30:54Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-a745b302d3a54c9b884b962e950893582022-12-22T04:40:06ZengBMCCancer Cell International1475-28672022-12-0122112010.1186/s12935-022-02741-5Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpointJun Yao0Ruoyu Gao1Minghan Luo2Defeng Li3Liliangzi Guo4Zichao Yu5Feng Xiong6Cheng Wei7Benhua Wu8Zhenglei Xu9Dingguo Zhang10Jianyao Wang11Lisheng Wang12Department of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalDepartment of General Surgery, Shenzhen Children’s HospitalDepartment of Gastroenterology, Jinan University of Second Clinical Medical Sciences, Shenzhen Municipal People’s HospitalAbstract Background Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC. Methods The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages. Results LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion. Conclusions LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.https://doi.org/10.1186/s12935-022-02741-5Pancreatic cancerLINC00460miR-503-5pANLNExosomesM2 polarization |
| spellingShingle | Jun Yao Ruoyu Gao Minghan Luo Defeng Li Liliangzi Guo Zichao Yu Feng Xiong Cheng Wei Benhua Wu Zhenglei Xu Dingguo Zhang Jianyao Wang Lisheng Wang Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint Cancer Cell International Pancreatic cancer LINC00460 miR-503-5p ANLN Exosomes M2 polarization |
| title | Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint |
| title_full | Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint |
| title_fullStr | Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint |
| title_full_unstemmed | Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint |
| title_short | Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint |
| title_sort | exosomal linc00460 mir 503 5p anln positive feedback loop aggravates pancreatic cancer progression through regulating t cell mediated cytotoxicity and pd 1 checkpoint |
| topic | Pancreatic cancer LINC00460 miR-503-5p ANLN Exosomes M2 polarization |
| url | https://doi.org/10.1186/s12935-022-02741-5 |
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