Lin28-let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras
- Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnamsi (Korea, Republic of)
- Department of Radiation Oncology, Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)
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.
- OSTI ID:
- 21367577
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 76, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2009.08.028; PII: S0360-3016(09)02969-1; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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CARCINOMAS
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DIGESTIVE SYSTEM
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GENE AMPLIFICATION
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