MICRORNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway

Chunzhi Zhang; Chunsheng Kang; Ping Wang; Yongzhen Cao; Zhonghong Lv; Shizhu Yu; Guangxiu Wang; Anling Zhang; Zhifan Jia; Lei Han; Chunying Yang; Hiromichi Ishiyama; Bin S. Teh; Bo Xu; Peiyu Pu

doi:10.1016/j.ijrobp.2010.12.049

MICRORNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway

Chunzhi Zhang, Chunsheng Kang, Ping Wang, Yongzhen Cao, Zhonghong Lv, Shizhu Yu, Guangxiu Wang, Anling Zhang, Zhifan Jia, Lei Han, Chunying Yang, Hiromichi Ishiyama, Bin S. Teh, Bo Xu, Peiyu Pu

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	240-248
Number of pages	9
Journal	International Journal of Radiation Oncology Biology Physics
Volume	80
Issue number	1
DOIs	https://doi.org/10.1016/j.ijrobp.2010.12.049
State	Published - May 1 2011

Keywords

miRNA-221
miRNA-222
PTEN
Radiosensitivity

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Radiation
Cancer Research

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10.1016/j.ijrobp.2010.12.049

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title = "MICRORNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway",

abstract = "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.",

keywords = "miRNA-221, miRNA-222, PTEN, Radiosensitivity",

author = "Chunzhi Zhang and Chunsheng Kang and Ping Wang and Yongzhen Cao and Zhonghong Lv and Shizhu Yu and Guangxiu Wang and Anling Zhang and Zhifan Jia and Lei Han and Chunying Yang and Hiromichi Ishiyama and Teh, \{Bin S.\} and Bo Xu and Peiyu Pu",

note = "Funding Information: This work was supported by National Natural Science Foundation of China Grants 30772231 and 30901772 , by the Program for New Century Excellent Talents in University ( NCET-07-0615 ), and by Tianjin Science and Technology Committee Grant 09JCZDJC17600 . B.X. was supported by Department of Defense grant W81XWH-05-1-0018 . Copyright: Copyright 2012 Elsevier B.V., All rights reserved.",

year = "2011",

month = may,

day = "1",

doi = "10.1016/j.ijrobp.2010.12.049",

language = "English (US)",

volume = "80",

pages = "240--248",

journal = "International Journal of Radiation Oncology Biology Physics",

issn = "0360-3016",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - MICRORNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway

AU - Zhang, Chunzhi

AU - Kang, Chunsheng

AU - Wang, Ping

AU - Cao, Yongzhen

AU - Lv, Zhonghong

AU - Yu, Shizhu

AU - Wang, Guangxiu

AU - Zhang, Anling

AU - Jia, Zhifan

AU - Han, Lei

AU - Yang, Chunying

AU - Ishiyama, Hiromichi

AU - Teh, Bin S.

AU - Xu, Bo

AU - Pu, Peiyu

N1 - Funding Information: This work was supported by National Natural Science Foundation of China Grants 30772231 and 30901772 , by the Program for New Century Excellent Talents in University ( NCET-07-0615 ), and by Tianjin Science and Technology Committee Grant 09JCZDJC17600 . B.X. was supported by Department of Defense grant W81XWH-05-1-0018 . Copyright: Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

KW - miRNA-221

KW - miRNA-222

KW - PTEN

KW - Radiosensitivity

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JF - International Journal of Radiation Oncology Biology Physics

IS - 1

ER -

MICRORNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway

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