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- Title
Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma.
- Authors
Iwai, Naoto; Yasui, Kohichiroh; Tomie, Akira; Gen, Yasuyuki; Terasaki, Kei; Kitaichi, Tomoko; Soda, Tomohiro; Yamada, Nobuhisa; Dohi, Osamu; Seko, Yuya; Umemura, Atsushi; Nishikawa, Taichiro; Yamaguchi, Kanji; Moriguchi, Michihisa; Konishi, Hideyuki; Naito, Yuji; Itoh, Yoshito
- 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 nontumorous 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 doxorubicinand 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.
- Publication
International Journal of Oncology, 2018, Vol 53, Issue 1, p237
- ISSN
1019-6439
- Publication type
Article
- DOI
10.3892/ijo.2018.4369