MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis

  • Authors:
    • Lei Shi
    • Shuguang Zhang
    • Kun Feng
    • Furong Wu
    • Yi Wan
    • Zhimin Wang
    • Junxia Zhang
    • Yinyi Wang
    • Wei Yan
    • Zhen Fu
    • Yongping You
  • View Affiliations

  • Published online on: August 29, 2011     https://doi.org/10.3892/ijo.2011.1179
  • Pages: 119-129
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Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. miR-125b, one of the neuronal miRNAs, was recently found to be necessary for stem cell fission and for making stem cells insensitive to chemotherapy signals. Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly and with a high frequency. Given the insensitivity of some glioblastomas to TMZ and the hypothesis that glioma stem cells cause resistance to drug therapy, exploring the functions and mechanisms of miR-125b action on TMZ-treated glioblastoma stem cells would be valuable. In this study, we found that miR-125b-2 is overexpressed in glioblastoma multiforme tissues and the corresponding stem cells (GBMSC); downregulation of miR-125b-2 expression in GBMSC could allow TMZ to induce GBMSC apoptosis. Additionally, the expression of the anti-apoptotic protein Bcl-2 was decreased after the TMZ+miR-125b-2 inhibitor treatment, while the expression of the proapoptotic protein Bax was increased. Further research demonstrated that the induction of apoptosis in GBMSC is also associated with increased cytochrome c release from mitochondria, induction of Apaf-1, activation of caspase-3 and poly-ADP-ribose polymerase (PARP). Taken together, these results suggest that miR-125b-2 overexpression might confer glioblastoma stem cells resistance to TMZ.

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January 2012
Volume 40 Issue 1

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

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Copy and paste a formatted citation
APA
Shi, L., Zhang, S., Feng, K., Wu, F., Wan, Y., Wang, Z. ... You, Y. (2012). MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis. International Journal of Oncology, 40, 119-129. https://doi.org/10.3892/ijo.2011.1179
MLA
Shi, L., Zhang, S., Feng, K., Wu, F., Wan, Y., Wang, Z., Zhang, J., Wang, Y., Yan, W., Fu, Z., You, Y."MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis". International Journal of Oncology 40.1 (2012): 119-129.
Chicago
Shi, L., Zhang, S., Feng, K., Wu, F., Wan, Y., Wang, Z., Zhang, J., Wang, Y., Yan, W., Fu, Z., You, Y."MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis". International Journal of Oncology 40, no. 1 (2012): 119-129. https://doi.org/10.3892/ijo.2011.1179