MicroRNA-34a/IL-6R pathway as a potential therapeutic target for ovarian high-grade serous carcinoma
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Ryo Yokomizo1,*, Nozomu Yanaihara1,*, Noriko Yamaguchi1, Misato Saito1, Ayako Kawabata1, Kazuaki Takahashi1, Masataka Takenaka1, Kyosuke Yamada1, Jason Solomon Shapiro1 and Aikou Okamoto1
1 Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
* These authors contributed equally to this work
Keywords: ovarian high-grade serous carcinoma;
Received: March 21, 2019 Accepted: June 29, 2019 Published: August 6, 2019
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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