MiR-29a Regulates Radiosensitivity in Human Intestinal Cells by Targeting PTEN Gene

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 stud...

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Bibliographic Details
Published in:Radiation research 2016-09, Vol.186 (3), p.292-301
Main Authors: Wang, Juan, Xu, Jinping, Fu, Jiamei, Yuan, Dexiao, Guo, Fei, Zhou, Cuiping, Shao, Chunlin
Format: Article
Language:English
Subjects:
Biotechnology
Cancer
Cell Line, Tumor
Colorectal carcinoma
Damage
Gene Expression Regulation, Neoplastic - radiation effects
Genes
Humans
Intestines - cytology
Intestines - metabolism
Intestines - radiation effects
Irradiation
Low level
MicroRNAs - genetics
Pathways
Phosphatidylinositol 3-Kinases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
PTEN Phosphohydrolase - genetics
Radiation Tolerance - genetics
REGULAR ARTICLES
Signal Transduction - radiation effects
Space life sciences
Strategy
Tumors
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Summary: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.
ISSN:0033-7587
1938-5404
DOI:10.1667/RR14428.1