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Cited by 163

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microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells

Open access
Comincini, Sergio, Allavena, Giulia, Palumbo, Silvia, Morini, Martina, Durando, Francesca, Angeletti, Francesca, Pirtoli, Luigi, Miracco, Clelia·2013·Cancer Biology & Therapy

Abstract

ATG7 is a key autophagy-promoting gene that plays a critical role in the regulation of cell death and survival of various cell types. We report here that microRNAs (miRNAs), a class of endogenous 22-24 nucleotide noncoding RNA molecules able to affect stability and translation of mRNA, may represent a novel mechanism for regulating ATG7 expression and therefore autophagy. We demonstrated that ATG7 is a potential target for miR-17, and this miRNA could negatively regulate ATG7 expression, resulting in a modulation of the autophagic status in T98G glioblastoma cells. Treatment of these tumor cells with the miR-17 mimic decreased, and with the antagomir increased, the expression of ATG7 protein. Dual luciferase reporter assay confirmed that a specific miR-17 binding sequence in the 3'-UTR of ATG7 contributed to the modulation of the expression of the gene by miR-17. Interestingly, our results showed that anti-miR-17 administration activated autophagy through autophagosome formation, as resulted by LC3B and ATG7 protein expression increase, and by the analysis of GFP-LC3 positive autophagosome vesicles in living cells. Furthermore, the autophagy activation by anti-miR-17 resulted in a decrease of the threshold resistance at temozolomide doses in T98G cells, while miR-17 modulation in U373-MG glioblastoma cells resulted in a sensitization to low ionizing radiation doses. Our study of the role of miR-17 in regulating ATG7 expression and autophagy reveals a novel function for this miRNA sequence in a critical cellular event with significant impacts in cancer development, progression and treatment.

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Metadata

Authors
Comincini, S., Allavena, G., Palumbo, S., Morini, M., Durando, F., Angeletti, F., Pirtoli, L., & Miracco, C.
Venue
Cancer Biology & Therapy
Published
2013-07-10
Volume
14
Issue
7
Pages
574-586
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
OpenAlex
W1975235759
Cited by
163
References
10
FWCI
5.38
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. https://app.cochat.ai/papers/10.4161/cbt.24597
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Comincini, S., Allavena, G., Palumbo, S., Morini, M., Durando, F., Angeletti, F., Pirtoli, L., & Miracco, C. (2013). microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. Cancer Biology & Therapy. https://doi.org/10.4161/cbt.24597

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