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Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downr...

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Autores principales: Koma, Ayaka, Asai, Shunichi, Minemura, Chikashi, Oshima, Sachi, Kinoshita, Takashi, Kikkawa, Naoko, Koshizuka, Keiichi, Moriya, Shogo, Kasamatsu, Atsushi, Hanazawa, Toyoyuki, Uzawa, Katsuhiro, Seki, Naohiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469660/
https://www.ncbi.nlm.nih.gov/pubmed/34576110
http://dx.doi.org/10.3390/ijms22189947
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author Koma, Ayaka
Asai, Shunichi
Minemura, Chikashi
Oshima, Sachi
Kinoshita, Takashi
Kikkawa, Naoko
Koshizuka, Keiichi
Moriya, Shogo
Kasamatsu, Atsushi
Hanazawa, Toyoyuki
Uzawa, Katsuhiro
Seki, Naohiko
author_facet Koma, Ayaka
Asai, Shunichi
Minemura, Chikashi
Oshima, Sachi
Kinoshita, Takashi
Kikkawa, Naoko
Koshizuka, Keiichi
Moriya, Shogo
Kasamatsu, Atsushi
Hanazawa, Toyoyuki
Uzawa, Katsuhiro
Seki, Naohiko
author_sort Koma, Ayaka
collection PubMed
description We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.
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spelling pubmed-84696602021-09-27 Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma Koma, Ayaka Asai, Shunichi Minemura, Chikashi Oshima, Sachi Kinoshita, Takashi Kikkawa, Naoko Koshizuka, Keiichi Moriya, Shogo Kasamatsu, Atsushi Hanazawa, Toyoyuki Uzawa, Katsuhiro Seki, Naohiko Int J Mol Sci Article We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC. MDPI 2021-09-14 /pmc/articles/PMC8469660/ /pubmed/34576110 http://dx.doi.org/10.3390/ijms22189947 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koma, Ayaka
Asai, Shunichi
Minemura, Chikashi
Oshima, Sachi
Kinoshita, Takashi
Kikkawa, Naoko
Koshizuka, Keiichi
Moriya, Shogo
Kasamatsu, Atsushi
Hanazawa, Toyoyuki
Uzawa, Katsuhiro
Seki, Naohiko
Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
title Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
title_full Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
title_fullStr Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
title_short Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma
title_sort impact of oncogenic targets by tumor-suppressive mir-139-5p and mir-139-3p regulation in head and neck squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469660/
https://www.ncbi.nlm.nih.gov/pubmed/34576110
http://dx.doi.org/10.3390/ijms22189947
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