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MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3

Serine/arginine (SR)-rich proteins that contain RS domains and SR repeats have diverse cellular functions including transcription, polyadenylation, translation, and RNA export. The splicing factor SRSF3, also termed SRp20, is the smallest member of the SR protein family and is a known proto-oncogene...

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Autores principales: Kim, Hye Ree, Shin, Chang Hoon, Lee, Hong, Choi, Kyung Hee, Nam, Do-Hyun, Ohn, Takbum, Kim, Hyeon Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352405/
https://www.ncbi.nlm.nih.gov/pubmed/28039456
http://dx.doi.org/10.18632/oncotarget.14184
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author Kim, Hye Ree
Shin, Chang Hoon
Lee, Hong
Choi, Kyung Hee
Nam, Do-Hyun
Ohn, Takbum
Kim, Hyeon Ho
author_facet Kim, Hye Ree
Shin, Chang Hoon
Lee, Hong
Choi, Kyung Hee
Nam, Do-Hyun
Ohn, Takbum
Kim, Hyeon Ho
author_sort Kim, Hye Ree
collection PubMed
description Serine/arginine (SR)-rich proteins that contain RS domains and SR repeats have diverse cellular functions including transcription, polyadenylation, translation, and RNA export. The splicing factor SRSF3, also termed SRp20, is the smallest member of the SR protein family and is a known proto-oncogene. Although it is implicated in the malignant phenotypes of various cancer cells, the molecular mechanism underlying SRSF3-mediated cancer progression is still obscure. We investigated here the oncogenic functions of SRSF3 in osteosarcoma U2OS cells. Knockdown of SRSF3 inhibited proliferation, clonogenicity, and metastatic potential including migration and invasion. It also decreased the level of miR-1908 independent of its host gene FADS1. Although FADS1 was not associated with SRSF3-mediated malignant properties, overexpression of miR-1908-5p increased cell proliferation, migration, and invasion, suggesting that miR-1908-5p is responsible for the oncogenic functions of SRSF3. Knockdown of SRSF3 decreased the expression of miR-1908-5p by inhibiting transactivation of NF-κB. We observed that miR-1908-5p downregulated NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB pathway by directly binding to the 3’UTR of NKIRAS2 mRNA. Consistent with overexpression of miR-1908-5p, knockdown of NKIRAS2 diminished the expression level of IκB-β and provoked translocation of NF-κB into the nucleus where it transcriptionally activates its target genes including miR-1908-5p expression, thus elevating the proliferation and metastatic potential. Taken together, our results demonstrate that SRSF3 confers the malignant characteristics on cancer cells via the SRSF3/miR-1908-5p/NKIRAS2 axis.
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spelling pubmed-53524052017-04-14 MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3 Kim, Hye Ree Shin, Chang Hoon Lee, Hong Choi, Kyung Hee Nam, Do-Hyun Ohn, Takbum Kim, Hyeon Ho Oncotarget Research Paper Serine/arginine (SR)-rich proteins that contain RS domains and SR repeats have diverse cellular functions including transcription, polyadenylation, translation, and RNA export. The splicing factor SRSF3, also termed SRp20, is the smallest member of the SR protein family and is a known proto-oncogene. Although it is implicated in the malignant phenotypes of various cancer cells, the molecular mechanism underlying SRSF3-mediated cancer progression is still obscure. We investigated here the oncogenic functions of SRSF3 in osteosarcoma U2OS cells. Knockdown of SRSF3 inhibited proliferation, clonogenicity, and metastatic potential including migration and invasion. It also decreased the level of miR-1908 independent of its host gene FADS1. Although FADS1 was not associated with SRSF3-mediated malignant properties, overexpression of miR-1908-5p increased cell proliferation, migration, and invasion, suggesting that miR-1908-5p is responsible for the oncogenic functions of SRSF3. Knockdown of SRSF3 decreased the expression of miR-1908-5p by inhibiting transactivation of NF-κB. We observed that miR-1908-5p downregulated NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB pathway by directly binding to the 3’UTR of NKIRAS2 mRNA. Consistent with overexpression of miR-1908-5p, knockdown of NKIRAS2 diminished the expression level of IκB-β and provoked translocation of NF-κB into the nucleus where it transcriptionally activates its target genes including miR-1908-5p expression, thus elevating the proliferation and metastatic potential. Taken together, our results demonstrate that SRSF3 confers the malignant characteristics on cancer cells via the SRSF3/miR-1908-5p/NKIRAS2 axis. Impact Journals LLC 2016-12-26 /pmc/articles/PMC5352405/ /pubmed/28039456 http://dx.doi.org/10.18632/oncotarget.14184 Text en Copyright: © 2017 Kim et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kim, Hye Ree
Shin, Chang Hoon
Lee, Hong
Choi, Kyung Hee
Nam, Do-Hyun
Ohn, Takbum
Kim, Hyeon Ho
MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3
title MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3
title_full MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3
title_fullStr MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3
title_full_unstemmed MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3
title_short MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3
title_sort microrna-1908-5p contributes to the oncogenic function of the splicing factor srsf3
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352405/
https://www.ncbi.nlm.nih.gov/pubmed/28039456
http://dx.doi.org/10.18632/oncotarget.14184
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