High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis
Abstract Recurrence is one of the major issues in bladder cancer (BCa). Novel technologies, such as the detection of microRNAs carried by extracellular vesicles (EVs) in urine, have been proposed as biomarkers for detecting recurrence in BCa. Although the usefulness of microRNAs in body fluids from...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Journal of Extracellular Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jex2.47 |
| _version_ | 1797766970930626560 |
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| author | Marta Prieto‐Vila Wataru Usuba Yusuke Yoshioka Fumitaka Takeshita Miki Yoshiike Hideo Sasaki Yusuke Yamamoto Eiji Kikuchi Takahiro Ochiya |
| author_facet | Marta Prieto‐Vila Wataru Usuba Yusuke Yoshioka Fumitaka Takeshita Miki Yoshiike Hideo Sasaki Yusuke Yamamoto Eiji Kikuchi Takahiro Ochiya |
| author_sort | Marta Prieto‐Vila |
| collection | DOAJ |
| description | Abstract Recurrence is one of the major issues in bladder cancer (BCa). Novel technologies, such as the detection of microRNAs carried by extracellular vesicles (EVs) in urine, have been proposed as biomarkers for detecting recurrence in BCa. Although the usefulness of microRNAs in body fluids from cancer patients has been reported, it is also known that they play essential roles in cancer progression. We previously proposed miR‐146a‐5p as a prognostic marker in BCa, since its urinary expression was associated with grade and tumour depth. However, the specific mechanisms of miR‐146a‐5p remain unclear. Here, we show the proangiogenic effects of miR‐146a‐5p secreted by high‐grade BCa cells. The urinary miR‐146a‐5p level was higher in patients with high‐grade BCa than in those with low‐grade BCa. Similarly, tumours generated by miR‐146a‐overexpressing BCa cells in mice grew rapidly with high levels of angiogenesis. BCa‐derived EV treatment promoted the proliferation of endothelial cells via the inhibition of the demethylase TET2 and the subsequent increase in its downstream target c‐Myc. These findings demonstrate that secreted miR‐146a‐5p contributes to cancer progression by promoting angiogenesis. Therefore, miRNAs in EVs may become not only a diagnostic tool but also a target molecule for therapy. |
| first_indexed | 2024-03-12T20:32:01Z |
| format | Article |
| id | doaj.art-224dc29930d8463986a0ee6d8a33a33b |
| institution | Directory Open Access Journal |
| issn | 2768-2811 |
| language | English |
| last_indexed | 2024-03-12T20:32:01Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Biology |
| spelling | doaj.art-224dc29930d8463986a0ee6d8a33a33b2023-08-01T19:00:31ZengWileyJournal of Extracellular Biology2768-28112022-08-0118n/an/a10.1002/jex2.47High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesisMarta Prieto‐Vila0Wataru Usuba1Yusuke Yoshioka2Fumitaka Takeshita3Miki Yoshiike4Hideo Sasaki5Yusuke Yamamoto6Eiji Kikuchi7Takahiro Ochiya8Department of Molecular and Cellular Medicine, Institute of Medical Science Tokyo Medical University Tokyo JapanDepartment of Urology St. Marianna University School of Medicine Kawasaki JapanDepartment of Molecular and Cellular Medicine, Institute of Medical Science Tokyo Medical University Tokyo JapanDivision of Fundamental Innovated Oncology National Cancer Center Research Institutes Tokyo JapanDepartment of Urology St. Marianna University School of Medicine Kawasaki JapanDepartment of Urology St. Marianna University School of Medicine Kawasaki JapanLaboratory of Integrative Oncology National Cancer Center Research Institute Tokyo JapanDepartment of Urology St. Marianna University School of Medicine Kawasaki JapanDepartment of Molecular and Cellular Medicine, Institute of Medical Science Tokyo Medical University Tokyo JapanAbstract Recurrence is one of the major issues in bladder cancer (BCa). Novel technologies, such as the detection of microRNAs carried by extracellular vesicles (EVs) in urine, have been proposed as biomarkers for detecting recurrence in BCa. Although the usefulness of microRNAs in body fluids from cancer patients has been reported, it is also known that they play essential roles in cancer progression. We previously proposed miR‐146a‐5p as a prognostic marker in BCa, since its urinary expression was associated with grade and tumour depth. However, the specific mechanisms of miR‐146a‐5p remain unclear. Here, we show the proangiogenic effects of miR‐146a‐5p secreted by high‐grade BCa cells. The urinary miR‐146a‐5p level was higher in patients with high‐grade BCa than in those with low‐grade BCa. Similarly, tumours generated by miR‐146a‐overexpressing BCa cells in mice grew rapidly with high levels of angiogenesis. BCa‐derived EV treatment promoted the proliferation of endothelial cells via the inhibition of the demethylase TET2 and the subsequent increase in its downstream target c‐Myc. These findings demonstrate that secreted miR‐146a‐5p contributes to cancer progression by promoting angiogenesis. Therefore, miRNAs in EVs may become not only a diagnostic tool but also a target molecule for therapy.https://doi.org/10.1002/jex2.47angiogenesisbladder cancercancerEVsmicroRNA |
| spellingShingle | Marta Prieto‐Vila Wataru Usuba Yusuke Yoshioka Fumitaka Takeshita Miki Yoshiike Hideo Sasaki Yusuke Yamamoto Eiji Kikuchi Takahiro Ochiya High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis Journal of Extracellular Biology angiogenesis bladder cancer cancer EVs microRNA |
| title | High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis |
| title_full | High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis |
| title_fullStr | High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis |
| title_full_unstemmed | High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis |
| title_short | High‐grade bladder cancer cells secrete extracellular vesicles containing miRNA‐146a‐5p and promotes angiogenesis |
| title_sort | high grade bladder cancer cells secrete extracellular vesicles containing mirna 146a 5p and promotes angiogenesis |
| topic | angiogenesis bladder cancer cancer EVs microRNA |
| url | https://doi.org/10.1002/jex2.47 |
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