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MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma

MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether tar...

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Detalles Bibliográficos
Autores principales: Ogawa, Himiko, Nakashiro, Koh‐ichi, Tokuzen, Norihiko, Kuribayashi, Nobuyuki, Goda, Hiroyuki, Uchida, Daisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226181/
https://www.ncbi.nlm.nih.gov/pubmed/32086979
http://dx.doi.org/10.1111/cas.14359
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author Ogawa, Himiko
Nakashiro, Koh‐ichi
Tokuzen, Norihiko
Kuribayashi, Nobuyuki
Goda, Hiroyuki
Uchida, Daisuke
author_facet Ogawa, Himiko
Nakashiro, Koh‐ichi
Tokuzen, Norihiko
Kuribayashi, Nobuyuki
Goda, Hiroyuki
Uchida, Daisuke
author_sort Ogawa, Himiko
collection PubMed
description MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether targeting these miRNAs might be useful in treatment for cancer. Functional screening for oncomiRs in a human OSCC cell line (GFP‐SAS) was carried out using the miRCURY LNA microRNA Knockdown Library – Human version 12.0. We identified a locked nucleic acid (LNA)/DNA antisense oligonucleotide against miR‐361‐3p (LNA‐miR‐361‐3p) which showed the largest degree of growth inhibition of GFP‐SAS cells. Transfection with a synthetic mimic of mature miR‐361‐3p resulted in an approximately 20% increase in the growth of GFP‐SAS cells. We identified odd‐skipped related 2 (OSR2) as a miR‐361‐3p target gene. Transfection of GFP‐SAS cells with LNA‐miR‐361‐3p caused a significant increase in the expression levels of OSR2. Cotransfection of a OSR2 3′‐UTR luciferase reporter plasmid and LNA‐miR‐361‐3p into GFP‐SAS cells produced higher levels of luciferase activity than in cells cotransfected with the LNA‐nontarget. We assessed the effect of LNA‐miR‐361‐3p on the in vivo growth of GFP‐SAS cells. We found that LNA‐miR‐361‐3p significantly reduced the size of s.c. xenografted GFP‐SAS tumors, compared to the control group treated with LNA‐NT. Finally, we observed that miR‐361‐3p is overexpressed in OSCC tissues. These results suggest that miR‐361‐3p supports the growth of human OSCC cells both in vitro and in vivo and that targeting miR‐361‐3p could be a useful therapeutic approach for patients with OSCC.
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spelling pubmed-72261812020-05-18 MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma Ogawa, Himiko Nakashiro, Koh‐ichi Tokuzen, Norihiko Kuribayashi, Nobuyuki Goda, Hiroyuki Uchida, Daisuke Cancer Sci Original Articles MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether targeting these miRNAs might be useful in treatment for cancer. Functional screening for oncomiRs in a human OSCC cell line (GFP‐SAS) was carried out using the miRCURY LNA microRNA Knockdown Library – Human version 12.0. We identified a locked nucleic acid (LNA)/DNA antisense oligonucleotide against miR‐361‐3p (LNA‐miR‐361‐3p) which showed the largest degree of growth inhibition of GFP‐SAS cells. Transfection with a synthetic mimic of mature miR‐361‐3p resulted in an approximately 20% increase in the growth of GFP‐SAS cells. We identified odd‐skipped related 2 (OSR2) as a miR‐361‐3p target gene. Transfection of GFP‐SAS cells with LNA‐miR‐361‐3p caused a significant increase in the expression levels of OSR2. Cotransfection of a OSR2 3′‐UTR luciferase reporter plasmid and LNA‐miR‐361‐3p into GFP‐SAS cells produced higher levels of luciferase activity than in cells cotransfected with the LNA‐nontarget. We assessed the effect of LNA‐miR‐361‐3p on the in vivo growth of GFP‐SAS cells. We found that LNA‐miR‐361‐3p significantly reduced the size of s.c. xenografted GFP‐SAS tumors, compared to the control group treated with LNA‐NT. Finally, we observed that miR‐361‐3p is overexpressed in OSCC tissues. These results suggest that miR‐361‐3p supports the growth of human OSCC cells both in vitro and in vivo and that targeting miR‐361‐3p could be a useful therapeutic approach for patients with OSCC. John Wiley and Sons Inc. 2020-03-18 2020-05 /pmc/articles/PMC7226181/ /pubmed/32086979 http://dx.doi.org/10.1111/cas.14359 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Ogawa, Himiko
Nakashiro, Koh‐ichi
Tokuzen, Norihiko
Kuribayashi, Nobuyuki
Goda, Hiroyuki
Uchida, Daisuke
MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
title MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
title_full MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
title_fullStr MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
title_full_unstemmed MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
title_short MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
title_sort microrna‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226181/
https://www.ncbi.nlm.nih.gov/pubmed/32086979
http://dx.doi.org/10.1111/cas.14359
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