Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras.
OBJECTIVE
To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling.


METHODS
A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed.


RESULTS
The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression and radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach.


CONCLUSIONS
The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.
Oh
Jee-Sun
JS
Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnamsi, Korea.
Kim
Jae-Jin
JJ
Byun
Ju-Yeon
JY
Kim
In-Ah
IA
D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects; D015870:Gene Expression; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000532:radiotherapy; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000532:radiotherapy; D034741:RNA, Small Interfering / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D014162:Transfection / Q000379:methods; D014410:Tumor Stem Cell Assay; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C000715187:Lin28A protein, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human; D018631:ras Proteins