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EnglishBreast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. Evidence suggests that CSCs contribute to chemotherapy resistance and to survival under hypoxic conditions. Interestingly, hypoxia in turn regulates self-renewal in CSCs and these effects may be primarily mediated by hypoxic inducible factors (HIFs). Recently, microRNAs (miRNAs) have emerged as critical players in the maintenance of pluripotency and self-renewal in normal and cancer stem cells. Here, we demonstrate that miR-24 is upregulated in breast CSCs and that its overexpression increases the number of mammospheres and the expression of stem cell markers. MiR-24 also induces apoptosis resistance through the regulation of BimL expression. Moreover, we identify a new miR-24 target, FIH1, which promotes HIFα degradation: miR-24 increases under hypoxic conditions, causing downregulation of FIH1 and upregulation of HIF1α. In conclusion, miR-24 hampers chemotherapy-induced apoptosis in breast CSCs and increases cell resistance to hypoxic conditions through an FIH1-HIFa pathway.
Roscigno G., Puoti I., Giordano I., Donnarumma E., Russo V., Affinito A., et al. (2017). MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer. ONCOTARGET, 8(12), 19507-19521.
| Data di pubblicazione: | 2017 |
| Titolo: | MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer |
| Autori: | |
| Citazione: | Roscigno G., Puoti I., Giordano I., Donnarumma E., Russo V., Affinito A., et al. (2017). MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer. ONCOTARGET, 8(12), 19507-19521. |
| Rivista: | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.18632/oncotarget.14470 |
| Abstract: | Breast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. Evidence suggests that CSCs contribute to chemotherapy resistance and to survival under hypoxic conditions. Interestingly, hypoxia in turn regulates self-renewal in CSCs and these effects may be primarily mediated by hypoxic inducible factors (HIFs). Recently, microRNAs (miRNAs) have emerged as critical players in the maintenance of pluripotency and self-renewal in normal and cancer stem cells. Here, we demonstrate that miR-24 is upregulated in breast CSCs and that its overexpression increases the number of mammospheres and the expression of stem cell markers. MiR-24 also induces apoptosis resistance through the regulation of BimL expression. Moreover, we identify a new miR-24 target, FIH1, which promotes HIFα degradation: miR-24 increases under hypoxic conditions, causing downregulation of FIH1 and upregulation of HIF1α. In conclusion, miR-24 hampers chemotherapy-induced apoptosis in breast CSCs and increases cell resistance to hypoxic conditions through an FIH1-HIFa pathway. |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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| Oncotarget 2017.pdf | Versione Editoriale | Open Access Visualizza/Apri |
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