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MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma

Accumulating evidence has indicated that microRNAs play a critical role in the pathogenesis of human cancers. microRNA-34a (miR-34a) has been shown to be a key regulator of tumor suppression by targeting several cancer-related signals, including the interleukin-6 receptor (IL-6R)/Signal Transducers...

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Autores principales: Yokomizo, Ryo, Yanaihara, Nozomu, Yamaguchi, Noriko, Saito, Misato, Kawabata, Ayako, Takahashi, Kazuaki, Takenaka, Masataka, Yamada, Kyosuke, Shapiro, Jason Solomon, Okamoto, Aikou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690672/
https://www.ncbi.nlm.nih.gov/pubmed/31448054
http://dx.doi.org/10.18632/oncotarget.27117
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author Yokomizo, Ryo
Yanaihara, Nozomu
Yamaguchi, Noriko
Saito, Misato
Kawabata, Ayako
Takahashi, Kazuaki
Takenaka, Masataka
Yamada, Kyosuke
Shapiro, Jason Solomon
Okamoto, Aikou
author_facet Yokomizo, Ryo
Yanaihara, Nozomu
Yamaguchi, Noriko
Saito, Misato
Kawabata, Ayako
Takahashi, Kazuaki
Takenaka, Masataka
Yamada, Kyosuke
Shapiro, Jason Solomon
Okamoto, Aikou
author_sort Yokomizo, Ryo
collection PubMed
description Accumulating evidence has indicated that microRNAs play a critical role in the pathogenesis of human cancers. microRNA-34a (miR-34a) has been shown to be a key regulator of tumor suppression by targeting several cancer-related signals, including the interleukin-6 receptor (IL-6R)/Signal Transducers and Activator of Transcription 3 (STAT3) signaling pathway. Previously, we determined that miR-34a expression was frequently reduced in high-grade serous carcinoma (HGSC), the major subtype of epithelial ovarian cancer (EOC). Considering that the IL-6R/STAT3 signaling pathway is upregulated and believed to be a potential therapeutic target in EOC, we investigated the biological significance of reduced miR-34a expression in HGSC with regard to IL-6R signaling. Additionally, we evaluated the viability of miR-34a as a therapeutic application for HGSC both in vitro and in vivo. Accordingly, we found that the ectopic expression of miR-34a significantly reduced tumor proliferation and invasion through downregulation of IL-6R expression, suggesting that reduced miR-34a expression might play an important role in the malignant potential of HGSC through upregulation of the IL-6R/STAT3 signaling pathway. Moreover, we demonstrated that replacement of miR-34a reduced tumorigenicity of HGSC in vivo. Therefore, this study may provide the rationale for miR-34a replacement as a promising therapeutic strategy for HGSC.
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spelling pubmed-66906722019-08-23 MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma Yokomizo, Ryo Yanaihara, Nozomu Yamaguchi, Noriko Saito, Misato Kawabata, Ayako Takahashi, Kazuaki Takenaka, Masataka Yamada, Kyosuke Shapiro, Jason Solomon Okamoto, Aikou Oncotarget Research Paper Accumulating evidence has indicated that microRNAs play a critical role in the pathogenesis of human cancers. microRNA-34a (miR-34a) has been shown to be a key regulator of tumor suppression by targeting several cancer-related signals, including the interleukin-6 receptor (IL-6R)/Signal Transducers and Activator of Transcription 3 (STAT3) signaling pathway. Previously, we determined that miR-34a expression was frequently reduced in high-grade serous carcinoma (HGSC), the major subtype of epithelial ovarian cancer (EOC). Considering that the IL-6R/STAT3 signaling pathway is upregulated and believed to be a potential therapeutic target in EOC, we investigated the biological significance of reduced miR-34a expression in HGSC with regard to IL-6R signaling. Additionally, we evaluated the viability of miR-34a as a therapeutic application for HGSC both in vitro and in vivo. Accordingly, we found that the ectopic expression of miR-34a significantly reduced tumor proliferation and invasion through downregulation of IL-6R expression, suggesting that reduced miR-34a expression might play an important role in the malignant potential of HGSC through upregulation of the IL-6R/STAT3 signaling pathway. Moreover, we demonstrated that replacement of miR-34a reduced tumorigenicity of HGSC in vivo. Therefore, this study may provide the rationale for miR-34a replacement as a promising therapeutic strategy for HGSC. Impact Journals LLC 2019-08-06 /pmc/articles/PMC6690672/ /pubmed/31448054 http://dx.doi.org/10.18632/oncotarget.27117 Text en Copyright: © 2019 Yokomizo 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 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yokomizo, Ryo
Yanaihara, Nozomu
Yamaguchi, Noriko
Saito, Misato
Kawabata, Ayako
Takahashi, Kazuaki
Takenaka, Masataka
Yamada, Kyosuke
Shapiro, Jason Solomon
Okamoto, Aikou
MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
title MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
title_full MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
title_fullStr MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
title_full_unstemmed MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
title_short MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
title_sort microrna-34a/il-6r pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690672/
https://www.ncbi.nlm.nih.gov/pubmed/31448054
http://dx.doi.org/10.18632/oncotarget.27117
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