Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma

  • Authors:
    • Naoto Iwai
    • Kohichiroh Yasui
    • Akira Tomie
    • Yasuyuki Gen
    • Kei Terasaki
    • Tomoko Kitaichi
    • Tomohiro Soda
    • Nobuhisa Yamada
    • Osamu Dohi
    • Yuya Seko
    • Atsushi Umemura
    • Taichiro Nishikawa
    • Kanji Yamaguchi
    • Michihisa Moriguchi
    • Hideyuki Konishi
    • Yuji Naito
    • Yoshito Itoh
  • View Affiliations

  • Published online on: April 12, 2018     https://doi.org/10.3892/ijo.2018.4369
  • Pages: 237-245
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Abstract

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.
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July 2018
Volume 53 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Iwai, N., Yasui, K., Tomie, A., Gen, Y., Terasaki, K., Kitaichi, T. ... Itoh, Y. (2018). Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma. International Journal of Oncology, 53, 237-245. https://doi.org/10.3892/ijo.2018.4369
MLA
Iwai, N., Yasui, K., Tomie, A., Gen, Y., Terasaki, K., Kitaichi, T., Soda, T., Yamada, N., Dohi, O., Seko, Y., Umemura, A., Nishikawa, T., Yamaguchi, K., Moriguchi, M., Konishi, H., Naito, Y., Itoh, Y."Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma". International Journal of Oncology 53.1 (2018): 237-245.
Chicago
Iwai, N., Yasui, K., Tomie, A., Gen, Y., Terasaki, K., Kitaichi, T., Soda, T., Yamada, N., Dohi, O., Seko, Y., Umemura, A., Nishikawa, T., Yamaguchi, K., Moriguchi, M., Konishi, H., Naito, Y., Itoh, Y."Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma". International Journal of Oncology 53, no. 1 (2018): 237-245. https://doi.org/10.3892/ijo.2018.4369