MiR-195, miR-455-3p and miR-10a* are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

Kenta Ujifuku, Norisato Mitsutake, Shu Takakura, Michiko Matsuse, Vladimir Saenko, Keiji Suzuki, Kentaro Hayashi, Takayuki Matsuo, Kensaku Kamada, Izumi Nagata, Shunichi Yamashita

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Abstract

To identify microRNAs (miRNAs) specifically involved in the acquisition of temozolomide (TMZ) resistance in glioblastoma multiforme (GBM), we first established a resistant variant, U251R cells from TMZ-sensitive GBM cell line, U251MG. We then performed a comprehensive analysis of miRNA expressions in U251R and parental cells using miRNA microarrays. miR-195, miR-455-3p and miR-10a* were the three most up-regulated miRNAs in the resistant cells. To investigate the functional role of these miRNAs in TMZ resistance, U251R cells were transfected with miRNA inhibitors consisting of DNA/LNA hybrid oligonucleotides. Suppression of miR-455-3p or miR-10a* had no effect on cell growth, but showed modest cell killing effect in the presence of TMZ. On the other hand, knockdown of miR-195 alone displayed moderate cell killing effect, and combination with TMZ strongly enhanced the effect. In addition, using in silico analysis combined with cDNA microarray experiment, we present possible mRNA targets of these miRNAs. In conclusion, our findings suggest that those miRNAs may play a role in acquired TMZ resistance and could be a novel target for recurrent GBM treatment.

Original languageEnglish
Pages (from-to)241-248
Number of pages8
JournalCancer Letters
Volume296
Issue number2
DOIs
Publication statusPublished - Oct 1 2010

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temozolomide
Glioblastoma
MicroRNAs
Oligonucleotide Array Sequence Analysis
Oligonucleotides
Computer Simulation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

MiR-195, miR-455-3p and miR-10a* are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. / Ujifuku, Kenta; Mitsutake, Norisato; Takakura, Shu; Matsuse, Michiko; Saenko, Vladimir; Suzuki, Keiji; Hayashi, Kentaro; Matsuo, Takayuki; Kamada, Kensaku; Nagata, Izumi; Yamashita, Shunichi.

In: Cancer Letters, Vol. 296, No. 2, 01.10.2010, p. 241-248.

Research output: Contribution to journalArticle

Ujifuku, K, Mitsutake, N, Takakura, S, Matsuse, M, Saenko, V, Suzuki, K, Hayashi, K, Matsuo, T, Kamada, K, Nagata, I & Yamashita, S 2010, 'MiR-195, miR-455-3p and miR-10a* are implicated in acquired temozolomide resistance in glioblastoma multiforme cells', Cancer Letters, vol. 296, no. 2, pp. 241-248. https://doi.org/10.1016/j.canlet.2010.04.013
Ujifuku, Kenta ; Mitsutake, Norisato ; Takakura, Shu ; Matsuse, Michiko ; Saenko, Vladimir ; Suzuki, Keiji ; Hayashi, Kentaro ; Matsuo, Takayuki ; Kamada, Kensaku ; Nagata, Izumi ; Yamashita, Shunichi. / MiR-195, miR-455-3p and miR-10a* are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. In: Cancer Letters. 2010 ; Vol. 296, No. 2. pp. 241-248.
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