Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth
ABSTRACT RNA modifications are crucial in cellular processes, and their dysregulation is linked to diseases like cancer. Extracellular vesicles (EVs) contain various RNAs and might be susceptible to modifications, but detecting these modifications has been challenging due to the small amount of RNA...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
|
| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.70083 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849717632647823360 |
|---|---|
| author | Yuya Monoe Kentaro Jingushi Kohei Taniguchi Kensuke Hirosuna Jun Arima Yosuke Inomata Yoshiaki Takano Hiroki Hamamoto Kazumasa Komura Tomohito Tanaka Hiroaki Hase Sang‐Woong Lee Kazutake Tsujikawa |
| author_facet | Yuya Monoe Kentaro Jingushi Kohei Taniguchi Kensuke Hirosuna Jun Arima Yosuke Inomata Yoshiaki Takano Hiroki Hamamoto Kazumasa Komura Tomohito Tanaka Hiroaki Hase Sang‐Woong Lee Kazutake Tsujikawa |
| author_sort | Yuya Monoe |
| collection | DOAJ |
| description | ABSTRACT RNA modifications are crucial in cellular processes, and their dysregulation is linked to diseases like cancer. Extracellular vesicles (EVs) contain various RNAs and might be susceptible to modifications, but detecting these modifications has been challenging due to the small amount of RNA in EVs. We successfully detected 22 RNA modifications in EVs using a proprietary ultra‐HPLC MS/MS system. We identified reduced levels of N6‐methyladenosine (m6A) in EVs derived from colon cancer tissues, which correlated with cancer recurrence. Increasing m6A levels via m6A demethylase Alkbh5 knockout suppressed the tumour‐promoting effects of colorectal cancer EVs. Mechanistically, colorectal cancer‐derived EVs increased tumour necrotic factor α and interleukin‐6 secretion by macrophages via Toll‐like receptor 8 in an m6A‐dependent manner, promoting cancer cell proliferation. RNA‐sequencing analysis showed that the levels of 5′‐half‐tRNA fragment (5′‐half)‐GlyGCC as well as those of m6A‐modified 5′‐half‐GlyGCC were higher and lower, respectively, in colorectal cancer EVs than in normal colon tissue EVs. Cancer‐derived EVs containing 5′‐half‐GlyGCC significantly promoted tumour growth, which was impeded by macrophage depletion. These findings provide evidence that cancer‐specific RNA modifications are present in EVs, promoting tumour progression by regulating immune cells. |
| format | Article |
| id | doaj-art-a0f7f5956bf849e092bbe201ec8794cd |
| institution | DOAJ |
| issn | 2001-3078 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-a0f7f5956bf849e092bbe201ec8794cd2025-08-20T03:12:35ZengWileyJournal of Extracellular Vesicles2001-30782025-05-01145n/an/a10.1002/jev2.70083Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour GrowthYuya Monoe0Kentaro Jingushi1Kohei Taniguchi2Kensuke Hirosuna3Jun Arima4Yosuke Inomata5Yoshiaki Takano6Hiroki Hamamoto7Kazumasa Komura8Tomohito Tanaka9Hiroaki Hase10Sang‐Woong Lee11Kazutake Tsujikawa12Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences Osaka University Suita Osaka JapanLaboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences Osaka University Suita Osaka JapanCenter for Medical Research & Development, Division of Translational Research Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanDepartment of Regenerative Science Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama JapanDepartment of General and Gastroenterological Surgery Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanDepartment of General and Gastroenterological Surgery Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanDepartment of General and Gastroenterological Surgery Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanDepartment of General and Gastroenterological Surgery Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanCenter for Medical Research & Development, Division of Translational Research Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanCenter for Medical Research & Development, Division of Translational Research Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanLaboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences Osaka University Suita Osaka JapanDepartment of General and Gastroenterological Surgery Osaka Medical and Pharmaceutical University Takatsuki Osaka JapanLaboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences Osaka University Suita Osaka JapanABSTRACT RNA modifications are crucial in cellular processes, and their dysregulation is linked to diseases like cancer. Extracellular vesicles (EVs) contain various RNAs and might be susceptible to modifications, but detecting these modifications has been challenging due to the small amount of RNA in EVs. We successfully detected 22 RNA modifications in EVs using a proprietary ultra‐HPLC MS/MS system. We identified reduced levels of N6‐methyladenosine (m6A) in EVs derived from colon cancer tissues, which correlated with cancer recurrence. Increasing m6A levels via m6A demethylase Alkbh5 knockout suppressed the tumour‐promoting effects of colorectal cancer EVs. Mechanistically, colorectal cancer‐derived EVs increased tumour necrotic factor α and interleukin‐6 secretion by macrophages via Toll‐like receptor 8 in an m6A‐dependent manner, promoting cancer cell proliferation. RNA‐sequencing analysis showed that the levels of 5′‐half‐tRNA fragment (5′‐half)‐GlyGCC as well as those of m6A‐modified 5′‐half‐GlyGCC were higher and lower, respectively, in colorectal cancer EVs than in normal colon tissue EVs. Cancer‐derived EVs containing 5′‐half‐GlyGCC significantly promoted tumour growth, which was impeded by macrophage depletion. These findings provide evidence that cancer‐specific RNA modifications are present in EVs, promoting tumour progression by regulating immune cells.https://doi.org/10.1002/jev2.700835′‐half‐GlyGCCcolorectal cancerextracellular vesiclesinflammatory cytokinesRNA modification |
| spellingShingle | Yuya Monoe Kentaro Jingushi Kohei Taniguchi Kensuke Hirosuna Jun Arima Yosuke Inomata Yoshiaki Takano Hiroki Hamamoto Kazumasa Komura Tomohito Tanaka Hiroaki Hase Sang‐Woong Lee Kazutake Tsujikawa Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth Journal of Extracellular Vesicles 5′‐half‐GlyGCC colorectal cancer extracellular vesicles inflammatory cytokines RNA modification |
| title | Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth |
| title_full | Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth |
| title_fullStr | Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth |
| title_full_unstemmed | Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth |
| title_short | Cancer‐Specific RNA Modifications in Tumour‐Derived Extracellular Vesicles Promote Tumour Growth |
| title_sort | cancer specific rna modifications in tumour derived extracellular vesicles promote tumour growth |
| topic | 5′‐half‐GlyGCC colorectal cancer extracellular vesicles inflammatory cytokines RNA modification |
| url | https://doi.org/10.1002/jev2.70083 |
| work_keys_str_mv | AT yuyamonoe cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT kentarojingushi cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT koheitaniguchi cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT kensukehirosuna cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT junarima cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT yosukeinomata cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT yoshiakitakano cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT hirokihamamoto cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT kazumasakomura cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT tomohitotanaka cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT hiroakihase cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT sangwoonglee cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth AT kazutaketsujikawa cancerspecificrnamodificationsintumourderivedextracellularvesiclespromotetumourgrowth |