Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma
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- Naoto Iwai
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Kohichiroh Yasui
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Akira Tomie
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Yasuyuki Gen
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Kei Terasaki
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Tomoko Kitaichi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Tomohiro Soda
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Nobuhisa Yamada
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Osamu Dohi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Yuya Seko
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Atsushi Umemura
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Taichiro Nishikawa
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Kanji Yamaguchi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Hideyuki Konishi
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Yuji Naito
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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- Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
書誌事項
- 公開日
- 2018-04-12
- 資源種別
- journal article
- DOI
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- 10.3892/ijo.2018.4369
- 公開者
- Spandidos Publications
この論文をさがす
説明
The aberrant expression or alteration of microRNAs (miRNAs/miRs) contributes to the development and progression of cancer. In the present study, the functions of miR-96-5p in hepatocellular carcinoma (HCC) were investigated. It was identified that miR-96-5p expression was significantly upregulated in primary HCC tumors compared with their non-tumorous counterparts. A copy number gain was frequently observed at chromosomal region 7q32.2 in which the MIR96 locus is located, suggesting that gene amplification may be one of the mechanisms by which miR-96-5p expression is increased in HCC. Transfection of miR-96-5p mimic into HCC cells decreased the expression of CASP9, which encodes caspase-9, the essential initiator caspase in the mitochondrial apoptotic pathway, at the mRNA and protein levels. A putative binding site for miR-96-5p was identified in the CASP9 3'-untranslated region, and the results of a luciferase assay indicated that CASP9 is a potential direct target of miR-96-5p. The miR-96-5p mimic increased resistance to doxorubicin- and ultraviolet-induced apoptosis through the decrease in caspase-9 expression in HCC cells. Transfection of miR-96-5p inhibitor enhanced the cytotoxic effect of doxorubicin by increasing caspase-9 expression in the HCC cells, suggesting a synergistic effect between the miR-96-5p inhibitor and doxorubicin. In conclusion, the results of the present study suggest that miR-96-5p, which is frequently upregulated in HCC, inhibits apoptosis by targeting CASP9. Therefore, miR-96-5p may be a potential therapeutic target for HCC.
収録刊行物
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- International Journal of Oncology
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International Journal of Oncology 2018-04-12
Spandidos Publications
