title: MiR-29a Regulates Radiosensitivity in Human Intestinal Cells by Targeting PTEN Gene.
abstract: 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.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Fu
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Dexiao
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000528:radiation effects*; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C532045:MIRN29a microRNA, human; C494929:PTEN protein, human