Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer
Background/Aims: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and m...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-11-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/495281 |
| _version_ | 1818572246199828480 |
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| author | Zhonghu Li Yang Tao Xiaoya Wang Peng Jiang Jie Li Minjie Peng Xi Zhang Kai Chen Hui Liu Ping Zhen Jin Zhu Xiangde Liu Xiangde Liu |
| author_facet | Zhonghu Li Yang Tao Xiaoya Wang Peng Jiang Jie Li Minjie Peng Xi Zhang Kai Chen Hui Liu Ping Zhen Jin Zhu Xiangde Liu Xiangde Liu |
| author_sort | Zhonghu Li |
| collection | DOAJ |
| description | Background/Aims: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and mechanisms of tumor-generated exosomal miRNAs in progression of PDAC. Methods: miR-222 was identified by miRNA microarray studies in exosomes of PDAC cells, and further analyzed in plasma exosomes of PDAC patients. The regulatory mechanisms of miR-222 were explored by qRT-PCR, WB, dual-luciferase assays and immunofluorescence or confocal analysis. Other biological assays include transwell, xenograft models and so on. Results: miR-222 is significantly high in tumor exosomes or highly invasive PDAC cells. miR-222 could directly regulate p27 to promote cell invasion and proliferation. miR-222 could also activate AKT by inhibiting PPP2R2A expression, thus inducing p27 phosphorylation and cytoplasmic p27 expression to promote cell survival, invasion and metastasis. Expressions of miR-222 and p27 were significantly inversely correlated, and cytoplasmic p27, instead of nuclear p27, was associated with tumor malignancy. miR-222 could be transmitted between PDAC cells via exosome communication, and the exosomal miR-222 communication is functional. Plasma exosomal miR-222 in PDAC patients was high and significantly correlated to tumor size and TNM stage, and was an independent risk factor for PDAC patient survival. Conclusion: Tumor-generated exosomes could promote invasion and proliferation of neighboring tumor cells via miR-222 transmission, the plasma exosomal miR-222 plays important roles and may be a useful prognostic maker in PDAC. |
| first_indexed | 2024-12-14T18:54:32Z |
| format | Article |
| id | doaj.art-4c8601a3baff4dca9b1473aa1d3f504b |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-14T18:54:32Z |
| publishDate | 2018-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-4c8601a3baff4dca9b1473aa1d3f504b2022-12-21T22:51:09ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-11-0151261062910.1159/000495281495281Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic CancerZhonghu LiYang TaoXiaoya WangPeng JiangJie LiMinjie PengXi ZhangKai ChenHui LiuPing ZhenJin ZhuXiangde LiuXiangde LiuBackground/Aims: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and mechanisms of tumor-generated exosomal miRNAs in progression of PDAC. Methods: miR-222 was identified by miRNA microarray studies in exosomes of PDAC cells, and further analyzed in plasma exosomes of PDAC patients. The regulatory mechanisms of miR-222 were explored by qRT-PCR, WB, dual-luciferase assays and immunofluorescence or confocal analysis. Other biological assays include transwell, xenograft models and so on. Results: miR-222 is significantly high in tumor exosomes or highly invasive PDAC cells. miR-222 could directly regulate p27 to promote cell invasion and proliferation. miR-222 could also activate AKT by inhibiting PPP2R2A expression, thus inducing p27 phosphorylation and cytoplasmic p27 expression to promote cell survival, invasion and metastasis. Expressions of miR-222 and p27 were significantly inversely correlated, and cytoplasmic p27, instead of nuclear p27, was associated with tumor malignancy. miR-222 could be transmitted between PDAC cells via exosome communication, and the exosomal miR-222 communication is functional. Plasma exosomal miR-222 in PDAC patients was high and significantly correlated to tumor size and TNM stage, and was an independent risk factor for PDAC patient survival. Conclusion: Tumor-generated exosomes could promote invasion and proliferation of neighboring tumor cells via miR-222 transmission, the plasma exosomal miR-222 plays important roles and may be a useful prognostic maker in PDAC.https://www.karger.com/Article/FullText/495281Pancreatic cancerExosomemiRNAP27Tumor invasionTumor prognosis |
| spellingShingle | Zhonghu Li Yang Tao Xiaoya Wang Peng Jiang Jie Li Minjie Peng Xi Zhang Kai Chen Hui Liu Ping Zhen Jin Zhu Xiangde Liu Xiangde Liu Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer Cellular Physiology and Biochemistry Pancreatic cancer Exosome miRNA P27 Tumor invasion Tumor prognosis |
| title | Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer |
| title_full | Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer |
| title_fullStr | Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer |
| title_full_unstemmed | Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer |
| title_short | Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer |
| title_sort | tumor secreted exosomal mir 222 promotes tumor progression via regulating p27 expression and re localization in pancreatic cancer |
| topic | Pancreatic cancer Exosome miRNA P27 Tumor invasion Tumor prognosis |
| url | https://www.karger.com/Article/FullText/495281 |
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