vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer

Fort Canobra, Rafael S - Garat, Beatriz - Sotelo Silveira, José Roberto - Duhagon, María Ana

Resumen:

vtRNA2-1 is a vault RNA initially classified as microRNA precursor hsa-mir-886 and recently proposed as “nc886”, a new type of non-coding RNA involved in cancer progression acting as an oncogene and tumor suppressor gene in different tissues. We have shown that vtRNA2-1/nc886 is epigenetically repressed in neoplastic cells, increasing cell proliferation and invasion in prostate tissue. Here we investigate the ability of vtRNA2-1/nc886 to produce small-RNAs and their biological effect in prostate cells. The interrogation of public small-RNA transcriptomes of prostate and other tissues uncovered two small RNAs, snc886-3p and snc886-5p, derived from vtRNA2-1/nc886 (previously hsa-miR-886-3p and hsa-miR-886-5p). Re-analysis of PAR-CLIP and knockout of microRNA biogenesis enzymes data showed that these small RNAs are products of DICER, independent of DROSHA, and associate with Argonaute proteins, satisfying microRNA attributes. In addition, the overexpression of snc886-3p provokes the downregulation of mRNAs bearing sequences complementary to its “seed” in their 3′-UTRs. Microarray and in vitro functional assays in DU145, LNCaP and PC3 cell lines revealed that snc886-3p reduced cell cycle progression and increases apoptosis, like its precursor vtRNA2-1/nc886. Finally, we found a list of direct candidate targets genes of snc886-3p upregulated and associated with disease condition and progression in PRAD-TCGA data. Overall, our findings suggest that vtRNA2-1/nc886 and its processed product snc886-3p are synthesized in prostate cells, exerting a tumor suppressor action


Detalles Bibliográficos
2020
vault RNA
vtRNA2-1
nc886
hsa-miR-886-3p
Cancer
Prostate
small RNA
microRNA
TCGA
PRAD
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/32305
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)
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author Fort Canobra, Rafael S
author2 Garat, Beatriz
Sotelo Silveira, José Roberto
Duhagon, María Ana
author2_role author
author
author
author_facet Fort Canobra, Rafael S
Garat, Beatriz
Sotelo Silveira, José Roberto
Duhagon, María Ana
author_role author
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dc.contributor.filiacion.none.fl_str_mv Fort Canobra Rafael S, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.
Garat Beatriz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.
Sotelo Silveira José Roberto, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.
Duhagon María Ana, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.
dc.creator.none.fl_str_mv Fort Canobra, Rafael S
Garat, Beatriz
Sotelo Silveira, José Roberto
Duhagon, María Ana
dc.date.accessioned.none.fl_str_mv 2022-06-22T14:53:51Z
dc.date.available.none.fl_str_mv 2022-06-22T14:53:51Z
dc.date.issued.none.fl_str_mv 2020
dc.description.abstract.none.fl_txt_mv vtRNA2-1 is a vault RNA initially classified as microRNA precursor hsa-mir-886 and recently proposed as “nc886”, a new type of non-coding RNA involved in cancer progression acting as an oncogene and tumor suppressor gene in different tissues. We have shown that vtRNA2-1/nc886 is epigenetically repressed in neoplastic cells, increasing cell proliferation and invasion in prostate tissue. Here we investigate the ability of vtRNA2-1/nc886 to produce small-RNAs and their biological effect in prostate cells. The interrogation of public small-RNA transcriptomes of prostate and other tissues uncovered two small RNAs, snc886-3p and snc886-5p, derived from vtRNA2-1/nc886 (previously hsa-miR-886-3p and hsa-miR-886-5p). Re-analysis of PAR-CLIP and knockout of microRNA biogenesis enzymes data showed that these small RNAs are products of DICER, independent of DROSHA, and associate with Argonaute proteins, satisfying microRNA attributes. In addition, the overexpression of snc886-3p provokes the downregulation of mRNAs bearing sequences complementary to its “seed” in their 3′-UTRs. Microarray and in vitro functional assays in DU145, LNCaP and PC3 cell lines revealed that snc886-3p reduced cell cycle progression and increases apoptosis, like its precursor vtRNA2-1/nc886. Finally, we found a list of direct candidate targets genes of snc886-3p upregulated and associated with disease condition and progression in PRAD-TCGA data. Overall, our findings suggest that vtRNA2-1/nc886 and its processed product snc886-3p are synthesized in prostate cells, exerting a tumor suppressor action
dc.format.extent.es.fl_str_mv 22 h.
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dc.identifier.citation.es.fl_str_mv Fort Canobra, R, Garat, B, Sotelo Silveira, J [y otros] "vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer". Non-Coding RNA. [en línea] 2020, 6(1): 7. 22 h. DOI: 10.3390/ncrna6010007
dc.identifier.doi.none.fl_str_mv 10.3390/ncrna6010007
dc.identifier.issn.none.fl_str_mv 2311-553X
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/32305
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv MDPI
dc.relation.ispartof.es.fl_str_mv Non-Coding RNA, 2020, 6(1): 7
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.es.fl_str_mv vault RNA
vtRNA2-1
nc886
hsa-miR-886-3p
Cancer
Prostate
small RNA
microRNA
TCGA
PRAD
dc.title.none.fl_str_mv vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description vtRNA2-1 is a vault RNA initially classified as microRNA precursor hsa-mir-886 and recently proposed as “nc886”, a new type of non-coding RNA involved in cancer progression acting as an oncogene and tumor suppressor gene in different tissues. We have shown that vtRNA2-1/nc886 is epigenetically repressed in neoplastic cells, increasing cell proliferation and invasion in prostate tissue. Here we investigate the ability of vtRNA2-1/nc886 to produce small-RNAs and their biological effect in prostate cells. The interrogation of public small-RNA transcriptomes of prostate and other tissues uncovered two small RNAs, snc886-3p and snc886-5p, derived from vtRNA2-1/nc886 (previously hsa-miR-886-3p and hsa-miR-886-5p). Re-analysis of PAR-CLIP and knockout of microRNA biogenesis enzymes data showed that these small RNAs are products of DICER, independent of DROSHA, and associate with Argonaute proteins, satisfying microRNA attributes. In addition, the overexpression of snc886-3p provokes the downregulation of mRNAs bearing sequences complementary to its “seed” in their 3′-UTRs. Microarray and in vitro functional assays in DU145, LNCaP and PC3 cell lines revealed that snc886-3p reduced cell cycle progression and increases apoptosis, like its precursor vtRNA2-1/nc886. Finally, we found a list of direct candidate targets genes of snc886-3p upregulated and associated with disease condition and progression in PRAD-TCGA data. Overall, our findings suggest that vtRNA2-1/nc886 and its processed product snc886-3p are synthesized in prostate cells, exerting a tumor suppressor action
eu_rights_str_mv openAccess
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id COLIBRI_5bb6339edf8cacca8021ee226e1b693a
identifier_str_mv Fort Canobra, R, Garat, B, Sotelo Silveira, J [y otros] "vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer". Non-Coding RNA. [en línea] 2020, 6(1): 7. 22 h. DOI: 10.3390/ncrna6010007
2311-553X
10.3390/ncrna6010007
instacron_str Universidad de la República
institution Universidad de la República
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language eng
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publishDate 2020
reponame_str COLIBRI
repository.mail.fl_str_mv mabel.seroubian@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
repository_id_str 4771
rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling Fort Canobra Rafael S, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica.Garat Beatriz, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Sotelo Silveira José Roberto, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Duhagon María Ana, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.2022-06-22T14:53:51Z2022-06-22T14:53:51Z2020Fort Canobra, R, Garat, B, Sotelo Silveira, J [y otros] "vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer". Non-Coding RNA. [en línea] 2020, 6(1): 7. 22 h. DOI: 10.3390/ncrna60100072311-553Xhttps://hdl.handle.net/20.500.12008/3230510.3390/ncrna6010007vtRNA2-1 is a vault RNA initially classified as microRNA precursor hsa-mir-886 and recently proposed as “nc886”, a new type of non-coding RNA involved in cancer progression acting as an oncogene and tumor suppressor gene in different tissues. We have shown that vtRNA2-1/nc886 is epigenetically repressed in neoplastic cells, increasing cell proliferation and invasion in prostate tissue. Here we investigate the ability of vtRNA2-1/nc886 to produce small-RNAs and their biological effect in prostate cells. The interrogation of public small-RNA transcriptomes of prostate and other tissues uncovered two small RNAs, snc886-3p and snc886-5p, derived from vtRNA2-1/nc886 (previously hsa-miR-886-3p and hsa-miR-886-5p). Re-analysis of PAR-CLIP and knockout of microRNA biogenesis enzymes data showed that these small RNAs are products of DICER, independent of DROSHA, and associate with Argonaute proteins, satisfying microRNA attributes. In addition, the overexpression of snc886-3p provokes the downregulation of mRNAs bearing sequences complementary to its “seed” in their 3′-UTRs. Microarray and in vitro functional assays in DU145, LNCaP and PC3 cell lines revealed that snc886-3p reduced cell cycle progression and increases apoptosis, like its precursor vtRNA2-1/nc886. Finally, we found a list of direct candidate targets genes of snc886-3p upregulated and associated with disease condition and progression in PRAD-TCGA data. Overall, our findings suggest that vtRNA2-1/nc886 and its processed product snc886-3p are synthesized in prostate cells, exerting a tumor suppressor actionSubmitted by Verdun Juan Pablo (jverdun@fcien.edu.uy) on 2022-06-17T19:17:20Z No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.3390ncrna6010007.pdf: 13632201 bytes, checksum: bbc6e133d571e3dd6c23824b9dc4ef25 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2022-06-22T14:22:27Z (GMT) No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.3390ncrna6010007.pdf: 13632201 bytes, checksum: bbc6e133d571e3dd6c23824b9dc4ef25 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2022-06-22T14:53:51Z (GMT). No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.3390ncrna6010007.pdf: 13632201 bytes, checksum: bbc6e133d571e3dd6c23824b9dc4ef25 (MD5) Previous issue date: 202022 h.application/pdfenengMDPINon-Coding RNA, 2020, 6(1): 7Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)vault RNAvtRNA2-1nc886hsa-miR-886-3pCancerProstatesmall RNAmicroRNATCGAPRADvtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancerArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaFort Canobra, Rafael SGarat, BeatrizSotelo Silveira, José RobertoDuhagon, María AnaLICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/32305/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; charset=utf-844http://localhost:8080/xmlui/bitstream/20.500.12008/32305/2/license_urla0ebbeafb9d2ec7cbb19d7137ebc392cMD52license_textlicense_texttext/html; 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- Universidad de la Repúblicafalse
spellingShingle vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
Fort Canobra, Rafael S
vault RNA
vtRNA2-1
nc886
hsa-miR-886-3p
Cancer
Prostate
small RNA
microRNA
TCGA
PRAD
status_str publishedVersion
title vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
title_full vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
title_fullStr vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
title_full_unstemmed vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
title_short vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
title_sort vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer
topic vault RNA
vtRNA2-1
nc886
hsa-miR-886-3p
Cancer
Prostate
small RNA
microRNA
TCGA
PRAD
url https://hdl.handle.net/20.500.12008/32305