Jee-Sun Oh, M.S.^*, Jae-Jin Kim, B.S.^*, Ju-Yeon Byun, M.S.^*, In-Ah Kim, M.D., Ph.D.<sup>*†

*</sup> Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnamsi, Korea
^*† Department of Radiation Oncology, Cancer Research Institute, Seoul National University, Seoul, Korea

Reprint requests to: In-Ah Kim, Department of Radiation Oncology, Seoul National University Bundang Hospital, 300 Gumidong Seongnamsi, Kyeonggido, Korea,

J.-S. Oh, J.-J. Kim, and J.-Y. B. contributed equally to this study.

Abstract
Purpose
To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling.

Methods and Materials
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.

Author Keywords : Lin28; let-7 microRNA; K-Ras