Two major challenges encountered during radiotherapy for colorectal cancer (CRC) are radioresistance of tumor cells and damage to normal cells. An understanding of the mechanisms of radioresistance in CRC may lead to new strategies for overcoming obstacles to affective clinical therapy. In this study, the miR-29a expression was compared among four cell lines: the normal human intestinal epithelial crypt cell line, HIEC and three CRC cell lines, HT29, DLD-1 and HCT116. The roles of miR-29a in regulating cellular radiosensitivity were then investigated. The findings from this study showed that miR-29a mimic enhanced radioresistance in HIEC, HT29 and DLD-1 cells with low levels of intrinsic miR-29a. On the other hand, a miR-29a inhibitor significantly sensitized HCT116 cells with high levels of miR-29a after irradiation. Further studies indicated that PTEN was the direct functional target of miR-29a and was involved in radiosensitivity. MiR-29a could activate the PI3K/Akt signaling pathway through negatively regulated PTEN expression. In conclusion, miR-29a may regulate the radiosensitivity of intestinal cell lines by targeting the PTEN gene, which indicates miR-29a might serve as a novel approach to enhance radiosensitivity in CRC.
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1 September 2016
Research Article|
August 22 2016
MiR-29a Regulates Radiosensitivity in Human Intestinal Cells by Targeting PTEN Gene
Juan Wang
;
Juan Wang
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Jinping Xu
;
Jinping Xu
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Jiamei Fu
;
Jiamei Fu
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Dexiao Yuan
;
Dexiao Yuan
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Fei Guo
;
Fei Guo
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Cuiping Zhou
;
Cuiping Zhou
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Chunlin Shao
Chunlin Shao
1
Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
1Address for correspondence: Fudan University, Institute of Radiation Medicine, No. 2094, Xie-Tu Road, Shanghai 200032, China; e-mail: clshao@shmu.edu.cn.
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Radiat Res (2016) 186 (3): 292–301.
Citation
Juan Wang, Jinping Xu, Jiamei Fu, Dexiao Yuan, Fei Guo, Cuiping Zhou, Chunlin Shao; MiR-29a Regulates Radiosensitivity in Human Intestinal Cells by Targeting PTEN Gene. Radiat Res 1 September 2016; 186 (3): 292–301. doi: https://doi.org/10.1667/RR14428.1
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