MicroRNA-221 and -222 Regulate Radiation Sensitivity by Targeting the PTEN Pathway

Journal Article · Sun May 01 04:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.12.049· OSTI ID:21491744

Chunzhi, Zhang ^[1]; Chunsheng, Kang ^[1]; Ping, Wang ^[2]; Yongzhen, Cao; Zhonghong, Lv ^[3]; Shizhu, Yu ^[4]; Guangxiu, Wang; Anling, Zhang; Zhifan, Jia; Lei, Han ^[1]; Chunying, Yang; Ishiyama, Hiromichi; Teh, Bin S ^[5]

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1. Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052 (China)
2. Department of Radiation Oncology, Cancer Institute and Hospital of Tianjin Medical University, Tianjin 300060 (China)
3. Department of Radiotherapy, Tianjin Medical University General Hospital, Tianjin 300052 (China)
4. Department of Neurology, Tianjin Medical University General Hospital, Laboratory of Neuro-pathology, Tianjin Neurological Institute, Tianjin 300052 (China)
5. Department of Radiation Oncology, Methodist Hospital Research Institute, Houston, Texas (United States)

Purpose: MicroRNAs (miRNAs) are noncoding RNAs inhibiting expression of numerous target genes by posttranscriptional regulation. miRNA-221 and miRNA-222 (miRNA-221/-222) expression is elevated in radioresistant tumor cell lines; however, it is not known whether and how miRNAs control cellular responses to ionizing irradiation. Methods and Materials: We used bioinformatic analyses, luciferase reporter assay, and genetic knockdown and biochemical assays to characterize the regulation pathways of miRNA-221/-222 in response to radiation treatment. Results: We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells. Conclusions: miRNA-221/-222 control radiation sensitivity by regulating the PTEN/AKT pathway and can be explored as novel targets for radiosensitization.

• OSTI ID: 21491744
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 80; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
APOPTOSIS
DNA
ENZYMES
GENES
LUCIFERASE
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
OXIDASES
OXIDOREDUCTASES
PROTEINS
RADIOSENSITIVITY
RNA
SENSITIVITY
TUMOR CELLS