The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines
Open accessAbstract
The resistance of hypoxic cells to radiotherapy and chemotherapy is a major problem in the treatment of cancer. Recently, an additional mode of hypoxia-inducible factor (HIF)-dependent transcriptional regulation, involving modulation of a specific set of micro RNAs (miRNAs), including miR-210, has emerged. We have recently shown that HIF-1 induction of miR-210 also stabilizes HIF-1 through a positive regulatory loop. Therefore, we hypothesized that by stabilizing HIF-1 in normoxia, miR-210 may protect cancer cells from radiation. We developed a non-small cell lung carcinoma (NSCLC)-derived cell line (A549) stably expressing miR-210 (pmiR-210) or a control miRNA (pmiR-Ctl). The miR-210-expressing cells showed a significant stabilization of HIF-1 associated with mitochondrial defects and a glycolytic phenotype. Cells were subjected to radiation levels ranging from 0 to 10 Gy in normoxia and hypoxia. Cells expressing miR-210 in normoxia had the same level of radioresistance as control cells in hypoxia. Under hypoxia, pmiR-210 cells showed a low mortality rate owing to a decrease in apoptosis, with an ability to grow even at 10 Gy. This miR-210 phenotype was reproduced in another NSCLC cell line (H1975) and in HeLa cells. We have established that radioresistance was independent of p53 and cell cycle status. In addition, we have shown that genomic double-strand breaks (DSBs) foci disappear faster in pmiR-210 than in pmiR-Ctl cells, suggesting that miR-210 expression promotes a more efficient DSB repair. Finally, HIF-1 invalidation in pmiR-210 cells removed the radioresistant phenotype, showing that this mechanism is dependent on HIF-1. In conclusion, miR-210 appears to be a component of the radioresistance of hypoxic cancer cells. Given the high stability of most miRNAs, this advantage could be used by tumor cells in conditions where reoxygenation has occurred and suggests that strategies targeting miR-210 could enhance tumor radiosensitization.
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Cites
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“By reducing the metabolism of mitochondria in normoxia, miR-210 would create a mitochondrial dysfunction that is known to lead to an increase in toxic reactive oxygen species (ROS).(25) Adaptation of cells to an increased ROS production may be part of the mechanism that protects cells against radiation exposure.”
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Self-citation
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Role of metabolism in cancer cell radioresistance and radiosensitization methods
Tang, L., Wei, F., Wu, Y., He, Y., Shi, L., Xiong, F., Gong, Z., Guo, C., Li, X., Deng, H., et al. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0758-7 · Cited by 409
The Roles of MicroRNA in Lung Cancer
Wu, K.-L., Tsai, Y.-M., Lien, C.-T., Kuo, P.-L., & Hung, J.-Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071611 · Cited by 284
Lung cancer epigenetics: From knowledge to applications
Duruisseaux, M., & Esteller, M. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.09.005 · Cited by 283
Targeting Hypoxia to Improve Non–Small Cell Lung Cancer Outcome
Salem, A., Asselin, M.-C., Reymen, B., Jackson, A., Lambin, P., West, C. M. L., O’Connor, J. P. B., & Faivre-Finn, C. (2018) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djx160 · Cited by 266
Non-Canonical Mechanisms Regulating Hypoxia-Inducible Factor 1 Alpha in Cancer
Iommarini, L., Porcelli, A. M., Gasparre, G., & Kurelac, I. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00286 · Cited by 231
Metadata
- Authors
- Grosso, S., Doyen, J., Parks, S. K., Bertero, T., Paye, A., Cardinaud, B., Gounon, P., Lacas-Gervais, S., Noël, A., Pouysségur, J., Barbry, P., Mazure, N. M., & Mari, B.
- Venue
- Cell Death & Disease
- Published
- 2013-03-14
- Volume
- 4
- Issue
- 3
- Pages
- e544-e544
- ISSN
- 2041-4889 (ISSN-L)
- OpenAlex
- W2024139498
- Cited by
- 216
- References
- 12
- FWCI
- 9.00
- Type
- journal article
- Language
- en
- Open access
- gold
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- Grosso, S., Doyen, J., Parks, S. K., Bertero, T., Paye, A., Cardinaud, B., Gounon, P., Lacas-Gervais, S., Noël, A., Pouysségur, J., Barbry, P., Mazure, N. M., & Mari, B. (2013). MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death & Disease. https://doi.org/10.1038/cddis.2013.71
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