Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1
Abstract Background Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. Methods Bioinformat...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01566-4 |
| _version_ | 1818299358510055424 |
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| author | Meng Wang Yi Zhao Zhi-Yun Yu Ren-De Zhang Shu-Ang Li Peng Zhang Ti-Kun Shan Xue-You Liu Ze-Ming Wang Pei-Chao Zhao Hong-Wei Sun |
| author_facet | Meng Wang Yi Zhao Zhi-Yun Yu Ren-De Zhang Shu-Ang Li Peng Zhang Ti-Kun Shan Xue-You Liu Ze-Ming Wang Pei-Chao Zhao Hong-Wei Sun |
| author_sort | Meng Wang |
| collection | DOAJ |
| description | Abstract Background Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. Methods Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. Results miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. Conclusion Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition. |
| first_indexed | 2024-12-13T04:49:57Z |
| format | Article |
| id | doaj.art-1dd706180ac54a25a23e7a2055c8dec8 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-13T04:49:57Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj.art-1dd706180ac54a25a23e7a2055c8dec82022-12-21T23:59:01ZengBMCCancer Cell International1475-28672020-10-0120111610.1186/s12935-020-01566-4Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1Meng Wang0Yi Zhao1Zhi-Yun Yu2Ren-De Zhang3Shu-Ang Li4Peng Zhang5Ti-Kun Shan6Xue-You Liu7Ze-Ming Wang8Pei-Chao Zhao9Hong-Wei Sun10Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Translational Medicine Center, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical, The Third Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. Methods Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. Results miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. Conclusion Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.http://link.springer.com/article/10.1186/s12935-020-01566-4GliomaAngiogenesisExosomal microRNA-148a-3pERBB receptor feedback inhibitor 1EGFR/MAPK pathway |
| spellingShingle | Meng Wang Yi Zhao Zhi-Yun Yu Ren-De Zhang Shu-Ang Li Peng Zhang Ti-Kun Shan Xue-You Liu Ze-Ming Wang Pei-Chao Zhao Hong-Wei Sun Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1 Cancer Cell International Glioma Angiogenesis Exosomal microRNA-148a-3p ERBB receptor feedback inhibitor 1 EGFR/MAPK pathway |
| title | Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1 |
| title_full | Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1 |
| title_fullStr | Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1 |
| title_full_unstemmed | Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1 |
| title_short | Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1 |
| title_sort | glioma exosomal microrna 148a 3p promotes tumor angiogenesis through activating the egfr mapk signaling pathway via inhibiting errfi1 |
| topic | Glioma Angiogenesis Exosomal microRNA-148a-3p ERBB receptor feedback inhibitor 1 EGFR/MAPK pathway |
| url | http://link.springer.com/article/10.1186/s12935-020-01566-4 |
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