miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles
Cancer cells shed a heterogenous mixture of extracellular vesicles (EVs), differing in both size and composition, which likely influence physiological processes in different manners. However, how cells differentially control the shedding of these EV populations is poorly understood. Here, we show th...
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2021
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oai:doaj.org-article:0a57c786ee194184bf255448133e7b112021-11-25T17:04:45ZmiR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles10.3390/cancers132258502072-6694https://doaj.org/article/0a57c786ee194184bf255448133e7b112021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5850https://doaj.org/toc/2072-6694Cancer cells shed a heterogenous mixture of extracellular vesicles (EVs), differing in both size and composition, which likely influence physiological processes in different manners. However, how cells differentially control the shedding of these EV populations is poorly understood. Here, we show that miR-1227, which is enriched in prostate cancer EVs, compared to the cell of origin, but not in EVs derived from prostate benign epithelial cells, induces the shedding of large EVs (such as large oncosomes), while inhibiting the shedding of small EVs (such as exosomes). RNA sequencing from cells stably expressing miR-1227, a modified RISCTRAP assay that stabilizes and purifies mRNA-miR-1227 complexes for RNA sequencing, and in silico target prediction tools were used to identify miR-1227 targets that may mediate this alteration in EV shedding. The COPII vesicle protein SEC23A emerged and was validated by qPCR, WBlot, and luciferase assays as a direct target of miR-1227. The inhibition of SEC23A was sufficient to induce the shedding of large EVs. These results identify a novel mechanism of EV shedding, by which the inhibition of SEC23A by miR-1227 induces a shift in EV shedding, favoring the shedding of large EV over small EV.Andrew ChinJavier MariscalMinhyung KimGiorgia GuerraBlandine VictorChen QianElisabetta BroseghiniEdwin PosadasMichael R. FreemanShivani SharmaPaolo GandelliniNadia ZaffaroniSungyong YouKeith Syson ChanJlenia GuarnerioMuller FabbriDolores Di VizioMDPI AGarticlelarge oncosomesextracellular vesiclesextracellular vesicle biogenesisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5850, p 5850 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
large oncosomes extracellular vesicles extracellular vesicle biogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
large oncosomes extracellular vesicles extracellular vesicle biogenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Andrew Chin Javier Mariscal Minhyung Kim Giorgia Guerra Blandine Victor Chen Qian Elisabetta Broseghini Edwin Posadas Michael R. Freeman Shivani Sharma Paolo Gandellini Nadia Zaffaroni Sungyong You Keith Syson Chan Jlenia Guarnerio Muller Fabbri Dolores Di Vizio miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles |
| description |
Cancer cells shed a heterogenous mixture of extracellular vesicles (EVs), differing in both size and composition, which likely influence physiological processes in different manners. However, how cells differentially control the shedding of these EV populations is poorly understood. Here, we show that miR-1227, which is enriched in prostate cancer EVs, compared to the cell of origin, but not in EVs derived from prostate benign epithelial cells, induces the shedding of large EVs (such as large oncosomes), while inhibiting the shedding of small EVs (such as exosomes). RNA sequencing from cells stably expressing miR-1227, a modified RISCTRAP assay that stabilizes and purifies mRNA-miR-1227 complexes for RNA sequencing, and in silico target prediction tools were used to identify miR-1227 targets that may mediate this alteration in EV shedding. The COPII vesicle protein SEC23A emerged and was validated by qPCR, WBlot, and luciferase assays as a direct target of miR-1227. The inhibition of SEC23A was sufficient to induce the shedding of large EVs. These results identify a novel mechanism of EV shedding, by which the inhibition of SEC23A by miR-1227 induces a shift in EV shedding, favoring the shedding of large EV over small EV. |
| format |
article |
| author |
Andrew Chin Javier Mariscal Minhyung Kim Giorgia Guerra Blandine Victor Chen Qian Elisabetta Broseghini Edwin Posadas Michael R. Freeman Shivani Sharma Paolo Gandellini Nadia Zaffaroni Sungyong You Keith Syson Chan Jlenia Guarnerio Muller Fabbri Dolores Di Vizio |
| author_facet |
Andrew Chin Javier Mariscal Minhyung Kim Giorgia Guerra Blandine Victor Chen Qian Elisabetta Broseghini Edwin Posadas Michael R. Freeman Shivani Sharma Paolo Gandellini Nadia Zaffaroni Sungyong You Keith Syson Chan Jlenia Guarnerio Muller Fabbri Dolores Di Vizio |
| author_sort |
Andrew Chin |
| title |
miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles |
| title_short |
miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles |
| title_full |
miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles |
| title_fullStr |
miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles |
| title_full_unstemmed |
miR-1227 Targets SEC23A to Regulate the Shedding of Large Extracellular Vesicles |
| title_sort |
mir-1227 targets sec23a to regulate the shedding of large extracellular vesicles |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/0a57c786ee194184bf255448133e7b11 |
| work_keys_str_mv |
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| _version_ |
1718412693133590528 |