Exp Mol Med.  2009 Dec;41(12):912-918. 10.3858/emm.2009.41.12.097.

LIN28B confers radio-resistance through the posttranscriptional control of KRAS

Affiliations
  • 1Department of Biomedical Sciences, Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea. wypark@snu.ac.kr
  • 2Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 110-799, Korea.
  • 3Department of Genomic Medicine Institute, MRC, Seoul National University College of Medicine, Seoul 110-799, Korea.
  • 4Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.

Abstract

To screen the differentially expressed microRNAs related to radio-resistance, we compared the microRNA profiles of lung cancer cells with different responses to ionizing radiation (IR). Of 328 microRNAs in microarray, 27 microRNAs were differentially expressed in NCI-H460 (H460) and NCI-H1299 (H1299) cells. Among them, let-7g was down-regulated in radio-resistant H1299 cells, and the level of let-7g was higher in radio-sensitive cells like Caski, H460, and ME180 in qRT-PCR analysis than in radio-resistant cells like A549, H1299, DLD1, and HeLa. Over-expression of let-7g in H1299 cells could suppress the translation of KRAS, and increase the sensitivity to IR. When we knockdown the expression of LIN28B, an upstream regulator of let-7g, the level of mature let-7g was increased in H1299 cells and the sensitivity to IR was also enhanced in LIN28B knockdown cells. From these data, we suggest that LIN28B plays an important role in radiation responses of lung cancer cells through inhibiting let-7g processing and increasing translation of KRAS.

Keyword

gene expression profiling; KRAS protein, human; LIN28B protein, human; lung neoplasms; microRNAs; mirnlet7 microRNA, human; radiation, ionizing

MeSH Terms

Cell Line, Tumor
DNA-Binding Proteins/*genetics/metabolism
Gene Expression Profiling
*Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms/*genetics
MicroRNAs/*genetics
Proto-Oncogene Proteins/*genetics/metabolism
*Radiation Tolerance
ras Proteins/*genetics/metabolism
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